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Biomedical subjects

L Wang

Publications and source records attributed to L Wang.

At least 1,045 records · Page 58Linked to original sources
PubMed1999

Dependence of NF-kappaB activation and free radical generation on silica-induced TNF-alpha production in macrophages.

Tumor necrosis factor alpha (TNFalpha) plays an important role in the pathogenesis of silicosis and other chronic inflammatory lung diseases. The present study investigates the role nuclear transcription factor kappaB (NF-kappaB) and oxygen free radicals in silica-induced TNFalpha production in primary alveolar macrophages and RAW 264.7 cells. Using electrophoretic mobility shift assay (EMSA) and enzyme-linked immunoadsorbent assay (ELISA), we have demonstrated that silica can induce NF-kappaB activation and TNFalpha expression in a dose-dependent manner. Transient transfection assays with a plasmid construct containing NF-kappaB binding sites linked to a reporter gene further show that silica is able to induce the transcriptional activation of NF-kappaB-dependent gene. Inhibition of NF-kappaB activation by SN50, a specific NF-kappaB blocker, abolishes silica-induced TNFalpha production. Pretreatment of the cells with catalase (H2O2 scavenger) or deferoxamine (*OH scavenger) effectively inhibits NF-kappaB and TNFalpha activation, whereas superoxide dismutase (O2 scavenger) has an opposite effect. These results indicate that silica-mediated free radical generation and NF-kappaB activation play important roles in silica-induced TNFalpha gene expression.

Animals↗
PubMed1999

Radiolabeled cholesteryl iopanoate/acetylated low density lipoprotein as a potential probe for visualization of early atherosclerotic lesions in rabbits.

PURPOSE: Atherosclerosis is the underlying factor leading to such cardiovascular diseases (CVD) as stroke, aneurysm, and myocardial infarction. The early detection of atherosclerotic plaques is considered to be crucial for successful prevention and/or therapeutic and dietary intervention of CVD. Current diagnostic practice, on the other hand, can only detect the problem at an advanced stage. The purpose of this study was to examine the potential of using a radiolabeled cholesterol ester analog/acetylated low density lipoprotein (AcLDL) conjugate as a diagnostic agent for the early and non-invasive detection of atherosclerosis and for the monitoring of the effects of drug therapy. METHODS: Cholesteryl iopanoate (CI), a cholesterylester analog, was synthesized, radiolabeled, and incorporated into AcLDL. Early atherosclerotic lesions were induced in New Zealand White rabbits. 125[-CI/AcLDL was injected intravenously at 2 microCi/kg. Blood samples were taken at different time intervals after injection and clearance of the injected drug from blood was studied. The rabbits were sacrificed after 72 hours and the distribution of radioactivity in various organs was investigated. Aortae of both atherosclerotic lesion and control rabbits were removed for Sudan IV staining and autoradiography in order to confirm the formation of the atherosclerotic lesion and localization of radioactivity. RESULTS: The injected drug was found to be cleared from blood following a two compartment model. Radioactivity in the atherosclerotic aorta was found to be about 8 times higher than that in normal aorta, suggesting that the proposed diagnostic probe was selectively taken up by the atherosclerotic lesion. The autoradiography and staining confirmed that the localization of the proposed probe was superimposed with the atherosclerotic lesion site. CONCLUSIONS: The results suggested that incorporation of CI into AcLDL resulted in the selective localization of CI at the atherosclerotic plaque areas. CI/AcLDL labeled with appropriate radioisotope has the potential to be used as a probe for visualization of early atherosclerotic lesion using scintigraphy technology.

Animals↗
PubMed1999

Inhibition of IL-6 in mice by anti-NF-kappaB oligodeoxyribonucleotide N3'-->oligodeoxyribonnucleotide N3' --> P5' phosphoramidates.

Oligonucleotide N3'->P5' Phosphoramidates (PN) may confer advantages over unmodified phosphodiester compounds for therapeutic applications (1). Previous in vitro data demonstrated that PN Oligodeoxynucleotides (ODNs) possess several advantageous features, including RNase H-independence, an improved resistance to nuclease degradation, decreased protein binding, and high affinity sequence-specific binding to complementary RNAs (1, 2). Consequently, we undertook a study to investigate the effects of PN antisense (AS) oligos targeted against the p65 subunit of the Nuclear Factor Kappa beta (NF-kappaB) transcription factor in vivo, in mice. The ability of the antisense molecules to inhibit IL-6 elevation induced by lipopolysaccharide (LPS) in mice, was studied. A 16 mer uniformly modified PN and a chimeric phosphoramidate-phosphodiester oligodeoxynucleotide complementary to the region surrounding the starting codon, (PN-PO-PN) of the NK-kappaB p65 subunit mRNA, both caused a sequence specific reduction of the serum IL-6 level in mice. A scrambled oligodeoxynucleotide showed much lower IL-6 inhibition in mice. These results show that the p65 PN-AS can modulate expression of IL-6 in mice without uptake enhancers and therefore may be a useful prototype for RNAse-H independent therapeutic agents.

Amides↗
PubMed1999

Association of heparin-induced skin lesions, intracutaneous tests, and heparin-induced IgG.

BACKGROUND: Cutaneous heparin-induced allergic reactions to subcutaneous heparin may begin 2-5 days after administration. The relation of the delayed-type hypersensitivity and a systemic immunologic response is controversial. The present investigation aimed to analyze the occurrence of thromboembolic complication, pathologic heparin-induced platelet activation (HIPA), and the presence of circulating heparin-induced IgG in patients with heparin-induced skin reactions. METHODS: Intracutaneous tests, HIPA assay, and heparin-heparin IgG antibodies were performed in nine patients with heparin-induced skin lesions. RESULTS: Six of eight patients showed positive intracutaneous tests to heparin and to four low-molecular-weight heparins. Three of six heparin-positive patients presented hypersensitivity to a heparinoid, too. Two of three patients had a positive HIPA test and elevated heparin-induced IgG antibodies. Both patients developed complications presenting as heparin-induced skin necrosis or arterial thrombosis. Two of nine patients were treated with danaparoid, 4/9 patients received r-hirudin, and 1/9 received oral coumarin. In 2/9 patients, anticoagulant therapy was stopped, but these patients will receive r-hirudin if indicated. CONCLUSIONS: On the basis of the coincidence of local and systemic hyperreactivity to heparin and danaparoid, patients with heparin-induced skin lesions should receive r-hirudin, a nonheparin compound, for anticoagulant treatment.

Adult↗
PubMed1999

Target site selection for an RNA-cleaving catalytic DNA.

A small catalytic DNA, known as the 10-23 DNA enzyme or deoxyribozyme, has been shown to efficiently hydrolyze RNA at purine-pyrimidine (R-Y) junctions in vitro. Although these potentially cleavable junctions are ubiquitous, they are often protected from deoxyribozyme activity by RNA secondary structure. We have developed a multiplex cleavage assay for screening the entire length of a target RNA molecule for deoxyribozyme cleavage sites that are efficient, both in terms of kinetics and accessibility. This strategy allowed us to simultaneously compare the RNA cleaving activity of 80 deoxyribozymes for a model target gene (HPV16 E6), and an additional 60 deoxyribozymes against the rat c-myc target. The human papilloma virus (HPV) target was used primarily to characterize the multiplex system and determine its validity. The c-myc target, coupled with a smooth muscle cell proliferation assay, allowed us to assess the relationship between in vitro cleavage efficiency and c-myc gene suppression in cell culture. The multiplex reaction approach streamlines the process of revealing effective deoxyribozymes in a functional assay and provides accessibility data that may also be applicable to site selection for other hybridization-based agents.

Animals↗
PubMed1999

A comparison of an A1 adenosine receptor agonist (CVT-510) with diltiazem for slowing of AV nodal conduction in guinea-pig.

1. The purpose of this study was to compare the pharmacological properties (i.e. the AV nodal depressant, vasodilator, and inotropic effects) of two AV nodal blocking agents belonging to different drug classes; a novel A1 adenosine receptor (A1 receptor) agonist, N-(3(R)-tetrahydrofuranyl)-6-aminopurine riboside (CVT-510), and the prototypical calcium channel blocker diltiazem. 2. In the atrial-paced isolated heart, CVT-510 was approximately 5 fold more potent to prolong the stimulus-to-His bundle (S-H interval), a measure of slowing AV nodal conduction (EC50 = 41 nM) than to increase coronary conductance (EC50 = 200 nM). At concentrations of CVT-510 (40 nM) and diltiazem (1 microM) that caused equal prolongation of S-H interval (approximately 10 ms), diltiazem, but not CVT-510, significantly reduced left ventricular developed pressure (LVP) and markedly increased coronary conductance. CVT-510 shortened atrial (EC50 = 73 nM) but not the ventricular monophasic action potentials (MAP). 3. In atrial-paced anaesthetized guinea-pigs, intravenous infusions of CVT-510 and diltiazem caused nearly equal prolongations of P-R interval. However, diltiazem, but not CVT-510, significantly reduced mean arterial blood pressure. 4. Both CVT-510 and diltiazem prolonged S-H interval, i.e., slowed AV nodal conduction. However, the A1 receptor-selective agonist CVT-510 did so without causing the negative inotropic, vasodilator, and hypotensive effects associated with diltiazem. Because CVT-510 did not affect the ventricular action potential, it is unlikely that this agonist will have a proarrythmic action in ventricular myocardium.

Action Potentials↗
PubMed1999

Presenilins interact with armadillo proteins including neural-specific plakophilin-related protein and beta-catenin.

Missense substitutions in the presenilin 1 (PS1) and presenilin 2 (PS2) proteins are associated with early-onset familial Alzheimer's disease. We have used yeast-two-hybrid and coimmunoprecipitation methods to show that the large cytoplasmic loop domains of PS1 and PS2 interact specifically with three members of the armadillo protein family, including beta-catenin, p0071, and a novel neuronal-specific armadillo protein--neural plakophilin-related armadillo protein (NPRAP). The PS1:NPRAP interaction occurs between the arm repeats of NPRAP and residues 372-399 at the C-terminal end of the large cytoplasmic loop of PS1. The latter residues contain a single arm-like domain and are highly conserved in the presenilins, suggesting that they form a functional armadillo protein binding site for the presenilins.

Alzheimer Disease↗
PubMed1999

Ultrasound-monitored effects of acupuncture on brain and eye.

A new transcranial Doppler sonography arrangement was used to monitor blood flow profiles in the supratrochlear and middle cerebral arteries simultaneously and continuously. The technique selectively demonstrated the specific effect of acupuncture on the cranial arteries, in a 25-year-old female with pigmentary retinopathy. Stimulation of points Zanzhu and Yuyao led to a marked increase of blood flow velocity in the supratrochlear artery and to a decrease of flow velocity, in the middle cerebral artery. These acupuncture-induced effects were reproducible even though both arteries originate from the same major vessel.

Acupuncture Therapy↗
PubMed1999

Computer-controlled acupuncture. Quantification and separation of specific effects.

The effects of acupuncture have been described and handed down empirically for centuries but there are few reports based on objective data. The aim of this study was to provide selective evidence of a specific effect of acupuncture on the brain and the eye using a Doppler ultrasound technique. A transcranial Doppler sonography arrangement was developed to monitor blood flow profiles in the supratrochlear and middle cerebral arteries simultaneously and continuously. Two acupuncture schemas were tested in a randomized cross-over study with 13 patients with ophthalmologic diseases. Applying acupuncture needles to special eye points increased the blood flow velocity in the supratrochlear artery significantly (p < 0.001) compared to the reference interval before acupuncture. In the middle cerebral artery only a minimal, non-significant increase in blood flow velocity was seen. In contrast, acupuncture of points that are held to increase cerebral blood flow velocity increased blood flow velocity in the middle cerebral artery significantly (p < 0.001) while leaving that in the supratrochlear artery unchanged. Specific acupuncture produce specific, reproducible quantifiable effects on blood flow velocity in arteries to the brain and eye.

Acupuncture Therapy↗
PubMed1999

Allele-specific late replication and fragility of the most active common fragile site, FRA3B.

FRA3B at 3p14.2 is the most active of the common fragile sites in the human genome and is expressed when cells are exposed to the DNA replication inhibitor, aphidicolin. Several lines of evidence suggest that fragile sites are regions of late replication. To elucidate the relationship between the timing of replication across the FRA3B region and its corresponding fragility, we labeled cells with 5-bromo-2'-deoxyuridine (BrdU) and adopted an immunofluorescent procedure to visualize late replicating DNA (BrdU-substituted DNA) in metaphase chromosomes. We also chose 21 markers along the FRA3B region and analyzed the timing of replication using BrdU-labeled DNA from different stages of the cell cycle sorted by flow cytometry. Our results show that there are two distinct alleles that replicate at different stages in the cell cycle and that breaks/gaps preferentially occurred on the chromosome 3 with the late replication allele. These results provide direct evidence that allele-specific late replication is involved in the fragility of the most active common fragile site, FRA3B.

Acid Anhydride Hydrolases↗
PubMed1999

Activation of the rostral ventrolateral medulla in an acute anesthetized rodent strychnine model of allodynia.

UNLABELLED: After the administration of intrathecal strychnine, allodynia is manifested as activation of supraspinal sites involved in pain processing and enhancement of cardiovascular responses evoked by normally innocuous stimuli. The objective of this study was to investigate the effect of strychnine-induced allodynia on adrenergic neuronal activity in the C1 area of the rostral ventrolateral medulla (RVLM), a major site involved in cardiovascular regulation. The effect of intrathecal strychnine (40 microg) or saline followed by repeated hair deflection to caudal lumbar dermatomes in the urethane-anesthetized rat was assessed by measuring voltammetric changes in the RVLM catechol oxidation current (CA x OC), mean arterial pressure (MAP), and heart rate (HR). After the administration of intrathecal strychnine, hair deflection evoked a significant and sustained increase in the RVLM CA x OC and MAP (peak 146.4%+/-5.6% and 159%+/-18.4% of baseline, respectively; P < 0.05). There was a nonsignificant increase in HR (peak 128%+/-8.2%). In the absence of hair deflection, there was no demonstrable change. Intrathecal saline-treated rats failed to demonstrate changes in RVLM CA x OC, MAP, or HR. In the present study, we demonstrated that, after the administration of intrathecal strychnine, innocuous hair deflection evokes temporally related neuronal activation in the rat RVLM and an increase in MAP. This suggests that the RVLM mediates, at least in part, the cardiovascular responses during strychnine allodynia. IMPLICATIONS: Neural injury-associated pain, as manifested by allodynia, is resistant to conventional treatment. In a rat model of allodynia, we demonstrated activation of the brain region involved in sympathetic control. Innovative therapies that target this region may be successful in managing this debilitating condition.

Anesthesia↗
PubMed1999

Growth factor receptors are differentially expressed in cancers of the papilla of vater and pancreas.

OBJECTIVE: To compare growth factor receptor expression in papilla of Vater cancer and pancreatic cancer. SUMMARY BACKGROUND DATA: Cancer of the papilla of Vater has a much better prognosis than pancreatic cancer. Earlier symptoms may result in earlier diagnosis, but different biologic growth behaviors and genetic alterations might also be explanations. PATIENTS AND METHODS: Surgical specimens from papilla of Vater cancers (24 patients) and pancreatic cancers (80 patients), normal papilla of Vater tissues (20 patients), and normal pancreatic tissues (24 patients) were frozen and fixed. The authors compared the expression of the epidermal growth factor receptor (EGFR) and c-erbB2 and c-erbB3 by Northern blot, in situ hybridization, and immunohistochemistry. RESULTS: In papilla of Vater cancer, Northern blots showed comparable EGFR and c-erbB2 mRNA expression but significantly lower c-erbB3 mRNA levels than in normal papilla. In pancreatic cancer, mRNA expression was enhanced compared with normal controls for EGFR (4-fold), c-erbB2 (2.5-fold), and c-erbB3 (5.2-fold). In situ hybridization confirmed this and showed mRNA expression only in cancer cells. EGFR immunohistochemical staining scores were comparable in papilla of Vater cancer (1.17 +/- 0.22) and normal papilla (1.42 +/- 0.25). Staining scores for c-erbB2 (2.72 +/- 0.40 vs. 3.89 +/- 0.37) and c-erbB3 (2.78 +/- 0.35 vs. 3.89 +/- 0.53) were slightly lower than controls in papilla of Vater cancer. In pancreatic cancer, immunostaining scores for EGFR, c-erbB2, and c-erbB3 were significantly higher than controls. CONCLUSION: Members of the EGFR family show similar or lower expression in papilla of Vater cancer than in normal controls. In pancreatic cancer, these receptors are upregulated. This supports the hypothesis that papilla of Vater cancer and pancreatic cancer have biologic differences that may contribute to the different growth of these tumors.

Adult↗
PubMed1999

Retroviral vector-mediated transfer and expression of human tissue plasminogen activator cDNA in bovine brain endothelial cells.

OBJECTIVES: Gene transfer of thrombolytic enzymes to vascular endothelial cells may influence the kinetics of intravascular thrombosis. This study defines the potential for gene transfer of tissue plasminogen activator (tPA) into bovine brain endothelial cells (BBEC). METHODS: The retroviral vectors derived from murine leukemia virus (MuLV) were used to transfer human tPA cDNA to BBEC. The tPA activity, tPA antigen and tPA inhibitor 1 (PAI-1) antigen were determined in the supernatant of transduced (BBEC/tPA) cell cultures by an immunoassay. RESULTS: The tPA antigen and enzymatic activity in cell culture supernatants of BBEC/tPA transduced cells were 75 ng/ml and 14 IU/ml after 4 days, that was 25 and 28-fold higher compared to the respective values in control cells. The PAI-1 antigen was not affected by tPA cDNA transfer. The Western blot assay of cell lysates confirmed that the majority of tPA in BBEC/tPA transduced cells was in the form of free tPA. While the maximal transduction efficiency of BBEC with an amphotropic MuLV vector was about 15%, a MuLV pseudotyped with vesicular stomatitis virus G glycoprotein envelope achieved high > 90% maximal transduction efficiency. CONCLUSIONS: The fibrinolytic activity of brain endothelial cells can be enhanced by transferring human tPA cDNA. These findings provide an initial step in implementation of future studies that investigate the use of this technology as an adjunctive treatment for cerebrovascular disease.

Animals↗
PubMed1999

Intracranial mucocele as a complication of endoscopic repair of cerebrospinal fluid rhinorrhea: case report.

OBJECTIVE AND IMPORTANCE: Endoscopic repair of an anterior cranial fossa cerebrospinal fluid (CSF) fistula has gained widespread acceptance. We report a case of mucocele development at the site of an endoscopic CSF leak repair. CLINICAL PRESENTATION: A 46-year-old woman underwent functional endoscopic sinus surgery for nasal obstructive symptoms. The surgery was complicated by an intraoperative CSF leak from the posterior cribriform plate/anterior sphenoid, which was repaired immediately using bone and mucosa grafts. Two years postoperatively, a 13-mm anterior cranial base mass was found incidentally. This mass increased to 20 mm over the next year. INTERVENTION: The anterior cranial base mass was excised via a right frontal craniotomy and confirmed histologically to be a mucocele. CONCLUSION: Endoscopic repair of an anterior cranial base CSF fistula with mucosal grafts may lead to formation of a mucocele.

Bone Transplantation↗
PubMed1999

Neurologic disease presenting as chronic pelvic pain.

Neurologic disease as a cause of chronic pelvic pain may be more common than previously reported. We report three cases wherein patients with complaints of pelvic pain were subsequently found to have neurologic disease involving the lumbosacral spine. In all three cases, the presenting features were complaints of cyclic or noncyclic lower abdominal pain attributed to endometriosis, pelvic inflammatory disease, or uterine fibroids. When conventional therapies failed to resolve the pain, magnetic resonance imaging (MRI) of the lumbosacral spine showed a neoplasm in one patient and disk herniation in two patients. Evolving lumbar disk disease or intradural neoplasms in the upper lumbar area can produce symptoms interpreted as pelvic pain. Symptoms consistent with radiculopathy occurred late in the course of each of the three cases reported.

Adult↗
PubMed1999

Study of the stability and unfolding mechanism of BBA1 by molecular dynamics simulations at different temperatures.

BBA1 is a designed protein that has only 23 residues. It is the smallest protein without disulfide bridges that has a well-defined tertiary structure in solution. We have performed unfolding molecular dynamics simulations on BBA1 and some of its mutants at 300, 330, 360, and 400 K to study their kinetic stability as well as the unfolding mechanism of BBA1. It was shown that the unfolding simulations can provide insights into the forces that stabilize the protein. Packing, hydrophobic interactions, and a salt bridge between Asp12 and Lys16 were found to be important to the protein's stability. The unfolding of BBA1 goes through two major steps: (1) disruption of the hydrophobic core and (2) unfolding of the helix. The beta-hairpin remains stable in the unfolding because of the high stability of the type II' turn connecting the two beta-strands.

Amino Acid Sequence↗
PubMed1999

An in vitro study of implant--tooth-supported connections using a robot test system.

Many unsolved problems in dental implant research concern the interfacial stress distributions between the implant components, as well as between the implant surface and contacting bone. To obtain a mechanical understanding of how vertical and horizontal occlusal forces are distributed in this context, it is crucial to develop in vitro testing systems to measure the force transmission between dental implants and attached prostheses. A new approach to such testing, involving a robotic system, is described in this investigation. The system has been designed to produce simulated mandibular movements and occlusal contact forces so that various implant designs and procedures can be thoroughly tested and evaluated before animal testing or human clinical trials. Two commonly used fixed prosthesis designs used to connect an implant and a tooth, a rigid connection and a nonrigid connection, were fabricated and used for experimental verification. The displacement and force distributions generated during simulated chewing activities were measured in vitro. Force levels, potentially harmful to human bone surrounding the connected dental implant and tooth, were analyzed. These results are useful in the design of prostheses and connecting components that will reduce failures and limit stress transfer to the implant/bone interface.

Computer Simulation↗