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Biomedical subjects

N Wang

Publications and source records attributed to N Wang.

At least 253 records · Page 14Linked to original sources

Genetic isolation of a chromosome 1 region affecting blood pressure in the spontaneously hypertensive rat.

Recent linkage studies in the spontaneously hypertensive rat (SHR) suggest that a blood pressure regulatory gene or genes may be located on rat chromosome 1q. To investigate this possibility, we replaced a region of chromosome 1 in the SHR (defined by the markers D1Mit3 and Igf2) with the corresponding chromosome segment from the normotensive Brown-Norway (BN) strain. In male SHR congenic rats carrying the transferred BN chromosome segment, 24-hour average systolic and diastolic blood pressures were significantly lower than in male progenitor SHR. Polymerase chain reaction genotyping using 60 polymorphic microsatellite markers dispersed throughout the genome confirmed the congenic status of the new strain designated SHR.BN-D1Mit3/Igf2. These findings provide direct evidence that a blood pressure regulatory gene exists on the differential segment of chromosome 1 that is sufficient to decrease blood pressure in the SHR. The SHR.BN-D1Mit3/Igf2 congenic strain represents an important new model for fine mapping and characterization of genes on chromosome 1 involved in the pathogenesis of spontaneous hypertension.

Animals↗

Cytoskeletal mechanics in pressure-overload cardiac hypertrophy.

We have shown that the cellular contractile dysfunction characteristic of pressure-overload cardiac hypertrophy results not from an abnormality intrinsic to the myofilament portion of the cardiocyte cytoskeleton but rather from an increased density of the microtubule component of the extramyofilament portion of the cardiocyte cytoskeleton. To determine how, in physical terms, this increased microtubule density mechanically overloads the contractile apparatus at the cellular level, we measured cytoskeletal stiffness and apparent viscosity in isolated cardiocytes via magnetic twisting cytometry, a technique by which magnetically induced force is applied directly to the cytoskeleton through integrin-coupled ferromagnetic beads coated with Arg-Gly-Asp (RGD) peptide. Measurements were made in two groups of cardiocytes from cats with right ventricular (RV) hypertrophy induced by pulmonary artery banding: (1) those from the pressure-overloaded RV and (2) those from the normally loaded same-animal control left ventricle (LV). Cytoskeletal stiffness increased almost twofold, from 8.53 +/- 0.77 dyne/cm2 in the normally loaded LV cardiocytes to 16.46 +/- 1.32 dyne/cm2 in the hypertrophied RV cardiocytes. Cytoskeletal apparent viscosity increased almost fourfold, from 20.97 +/- 1.92 poise in the normally loaded LV cardiocytes to 87.85 +/- 6.95 poise in the hypertrophied RV cardiocytes. In addition to these baseline data showing differing stiffness and, especially, apparent viscosity in the two groups of cardiocytes, microtubule depolymerization by colchicine was found to return both the stiffness and the apparent viscosity of the pressure overload-hypertrophied RV cells fully to normal. Conversely, microtubule hyperpolymerization by taxol increased the stiffness and apparent viscosity values of normally loaded LV cardiocytes to the abnormal values given above for pressure-hypertrophied RV cardiocytes. Thus, increased microtubule density constitutes primarily a viscous load on the cardiocyte contractile apparatus in pressure-overload cardiac hypertrophy.

Animals↗

Synthesis, characterization, biodegradation, and drug delivery application of biodegradable lactic/glycolic acid oligomers: I. Synthesis and characterization.

A series of oligomers or low molecular weight polymers of lactic and/or glycolic acid has been synthesized with different molar ratios of lactic to glycolic acid. These oligomers have been characterized with respect to oligomer composition, molecular weight, intrinsic viscosity, crystallinity, melting temperature, and glass transition temperature. The polymerization conditions for the lactic/glycolic acid oligomer syntheses were as follows: 180-220 degrees C, 5 mm Hg, 5 h, and 0.1 wt% of catalyst (antimony oxide) concentration. The polymeric compositions correlated to the feed ratios of lactic to glycolic acid. The molecular weight of the oligomers ranged from 895.8 +/- 48.7 to 1368.0 +/- 0 D with the intrinsic viscosity ranging from 0.0513 to 0.0814 dl g-1. The lactic/glycolic acid oligomers were found to be amorphous. The glass transition temperatures of the lactic/glycolic acid oligomers were lower than physiological temperature.

Biodegradation, Environmental↗

Synthesis, characterization, biodegradation, and drug delivery application of biodegradable lactic/glycolic acid oligomers: Part II. Biodegradation and drug delivery application.

Previously synthesized lactic/glycolic acid (PLGA) oligomers with different compositions (i.e. different ratio of lactic to glycolic acid in the oligomers) were further studied regarding their biodegradation and drug delivery application. The PLGA oligomers have fast biodegradation characteristics. They degrade to water soluble substances, i.e. lactic and glycolic acids, at a rate of 31.43-40.68 mg day-1 in a medium of constant pH and 28.04-37.87 mg day-1 in a medium of non-constant pH. The biodegradation rate is affected by the composition of the PLGA oligomers and the pH of the incubating medium. The higher the content of glycolic acid moiety in the oligomer, the faster the biodegradation rate. The lower the pH of the incubating medium, the slower the biodegradation of PLGA oligomers. A sustained-release drug delivery system based on the PLGA oligomers was fabricated as injectable microgranules by thermal blending of the PLGA oligomers and drug. Aspirin was used as a model drug. The oligomeric microgranules have advantages of easy fabrication, high drug loading efficiency, easy administration, and fast biodegradation. This thermal blending preparation method has a high loading efficiency of more than 90%. The PLGA oligomeric microgranules can release drug from 9 to 13 days depending on the oligomer composition. Both drug release rate and release duration are influenced by composition of the oligomers. The PLGA oligomeric matrix has the capability of protecting aspirin from hydrolysis. The lactic/glycolic acid oligomeric microgranules have potential use for sustained-release drug delivery.

Aspirin↗

Histidine kinases in signal transduction pathways of eukaryotes.

Autophosphorylating histidine kinases are an ancient conserved family of enzymes that are found in eubacteria, archaebacteria and eukaryotes. They are activated by a wide range of extracellular signals and transfer phosphate moieties to aspartates found in response regulators. Recent studies have shown that such two-component signal transduction pathways mediate osmoregulation in Saccharomyces cerevisiae, Dictyostelium discoideum and Neurospora crassa. Moreover, they play pivotal roles in responses of Arabidopsis thaliana to ethylene and cytokinin. A transmembrane histidine kinase encoded by dhkA accumulates when Dictyostelium cells aggregate during development. Activation of DhkA results in the inhibition of its response regulator, RegA, which is a cAMP phosphodiesterase that regulates the cAMP dependent protein kinase PKA. When PKA is activated late in the differentiation of prespore cells, they encapsulate into spores. There is evidence that this two-component system participates in a feedback loop linked to PKA in prestalk cells such that the signal to initiate encapsulation is rapidly amplified. Such signal transduction pathways can be expected to be found in a variety of eukaryotic differentiations since they are rapidly reversible and can integrate disparate signals.

Animals↗

Binding of urokinase to plasminogen activator inhibitor type-1 mediates cell adhesion and spreading.

Urokinase plasminogen activator and its receptor are both found at the surface of the cell membrane in many cell types. The plasminogen activator inhibitor type-1 (PAI-1) is often associated with the extracellular matrix. The spatial localization of these three molecules could account for their involvement in cell adhesion and/or migration. We have shown previously that the urokinase receptor mediates mechanical force transmission across the cell surface to the cytoskeleton. Here we investigated whether immobilized plasminogen activator inhibitor type 1 (PAI-1) could regulate cell spreading and cytoskeleton reorganization. Serum deprived human myogenic cells were plated in serum free medium onto bacteriologic dishes precoated with different extracellular matrix ligands (fibronectin, vitronectin, or type 1 collagen) or PAI-1 at increasing concentrations. The number of adherent cells and their projected area were quantitated after 3 hours of plating. PAI-1 promoted cell adhesion and spreading in a dose dependent manner. Addition of antibodies to PAI-1 inhibited the adhesion on PAI-1 coated dishes in a dose dependent way. The PAI-1 mediated cell adhesion required the presence of urokinase at the cell surface. Removal of the glycosylphosphatidylinositol (GPI)-linked proteins abolished cell adhesion on PAI-1 dish, suggesting its dependence on the presence of the urokinase receptor, a GPI-linked receptor. Furthermore, addition of antibodies against alpha v beta3 integrin completely inhibited cell adhesion on PAI-1, suggesting that alpha v beta3 might be the transmembrane molecule that physically connects the complex of PAI-1, urokinase, and urokinase receptor to the cytoskeleton. Visualization of spread cells stained for filamentous actin with confocal microscopy showed a dose-dependent increase of filopodia on PAI-1 coated dishes and cytoskeletal reorganization, suggesting a migratory profile. These data indicate that PAI-1 plays a direct role in dynamic cell adhesion particularly at the leading edge, where increased levels of urokinase plasminogen activator (uPA) and its receptor (uPAR) are localized in migrating cells. Immobilized PAI-1 could therefore serve to bridge the cell surface with the extracellular matrix via the formation of a multimolecular complex that includes alpha v beta3 integrins in myogenic cells.

Antibodies↗

The avian respiratory system: a unique model for studies of respiratory toxicosis and for monitoring air quality.

There are many distinct differences (morphologic, physiologic, and mechanical) between the bird's lung-air-sac respiratory system and the mammalian bronchoalveolar lung. In this paper, we review the physiology of the avian respiratory system with attention to those mechanisms that may lead to significantly different results, relative to those in mammals, following exposure to toxic gases and airborne particulates. We suggest that these differences can be productively exploited to further our understanding of the basic mechanisms of inhalant toxicology (gases and particulates). The large mass-specific gas uptake by the avian respiratory system, at rest and especially during exercise, could be exploited as a sensitive monitor of air quality. Birds have much to offer in our understanding of respiratory toxicology, but that expectation can only be realized by investigating, in a wide variety of avian taxa, the pathophysiologic interactions of a broad range of inhaled toxicants on the bird's unique respiratory system.

Aerosols↗

Post-translational processing of human procorticotrophin-releasing factor in transfected mouse neuroblastoma and Chinese hamster ovary cell lines.

The mouse neuroblastoma cell line (Neuro 2 A) has been shown to contain the mRNA of a prohormone converting enzyme, PC2. The Chinese hamster ovary cell line (CHO) does not express PC2 mRNA, but is thought to contain the ubiquitous protease, furin. The enzyme(s) responsible for releasing corticotrophin-releasing hormone (CRH) from its precursor (proCRH) have not been identified, therefore to investigate the possible function(s) of PC2 or furin in the processing of proCRH, stable Neuro 2 A and CHO cell lines that express the 21 kDa human (h)proCRH were established. A specific two-site IRMA for CRH demonstrated that the hpreproCRH-expressing Neuro 2 A cell line cleaved the CRH precursor to the CRH peptide, and was able to release the mature peptide into cell medium at levels that were 4-fold higher than produced by the hproCRH-expressing CHO cells. RIA showed that the CHO cells secreted levels of CRH-containing peptides that were 10-fold higher than produced by the Neuro 2 A cells. Medium from the transfected CHO and Neuro 2 A cells was analysed by HPLC; this showed that CHO cells released a single protein corresponding to the unprocessed CRH precursor, whereas Neuro 2 A cells secreted two peptides, which could be identified as the 5 kDa CRH(1-41) and residual 16 kDa CRH peptides. These results suggest that Neuro 2 A cells, which contain PC2, can process proCRH to the mature peptide.

Animals↗

Preparation and characterization of agarose hydrogel nanoparticles for protein and peptide drug delivery.

The purpose of this work was to develop and characterize a protein and peptide injectable drug delivery system in agarose hydrogel nanoparticles. The nanoparticles were prepared by using a new emulsion-converted-to-suspension in situ method. This is an emulsifier-free method that has advantages for protein and peptide drug encapsulations. Ovalbumin, used as a model protein drug, was successfully encapsulated into nearly spherical agarose hydrogel nanoparticles under mild conditions. The nanoparticles possessed a log-normal size distribution with an average size of 504 nm. They imbibed a large amount of water (66.85% to 84.33%) and the water content was a function of temperature; the water content increased with increase in temperature. Release studies of the ovalbumin from the agarose hydrogel nanoparticles revealed a diffusion-controlled release mechanism with a temperature dependence; the ovalbumin release rate was higher at 37 degrees C than that at room temperature. The great biocompatibility of agarose hydrogel, plus the mild conditions for drug encapsulation, make the agarose hydrogel nanoparticles a potential system for protein and peptide drug delivery.

Cross-Linking Reagents↗

[Study on Servo-null method for direct measurement of microvascular pressure by micropuncture technique].

The dynamic microvascular pressures in the mesentery of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were measured and recorded by using the Servo-null microvascular pressure measuring system (Model 4A, IPM, Inc., San Diego, USA) with glass micropipettes whose tips were 1.0-5.0 microns in diameter and had been beveled very sharply at an angle of 25 degree. Microvascular pressures were measured in two groups of microvessels: large, 25-45 microns; small, 15-25 microns. Mean microvascular pressures (Pm) of large and small arterial microvessels in SHR were 6.0 +/- 7.0 kPa and 4.8 +/- 0.6 kPa, respectively. In WKY rats, Pm were 4.2 +/- 0.6 kPa and 3.6 +/- 0.6 kPa, respectively. Pm of comparable types of arterial microvessels in SHR and WKY rats was significantly different. No significant difference of Pm in small venous vessels was found between SHR and WKY rats.

Animals↗

[The effect of antibody against vascular endothelial growth factor on tumor growth].

OBJECTIVE: Vascular endothelial growth factor (VEGF) is a very important factor in the process of angiogenesis, which is chosen as a target for experimental study of anticancer. METHODS: Anti-VEGF antibody was obtained from immunized rabbits and purified with affinity column. Morever, it was identified as neutralized antibody by Mile's assay. RESULTS: The anti-VEGF antibody was able to inhibit growth of S180 sarcoma in a dose-dependent manner, and the inhibition rate reached 41.0% with dose 200 micrograms per mouse per day. For human gastric cancer (MGC-803)-bearing nude mice, Anti-VEGF antibody inhibited tumor growth by 76.2%. When anti-VEGF antibody was combined with 131I-3H11, a murine monoclonal antibody conjugated with 131I for treatment, only one of five nude mice developed tumor and 84.0% more inhibition of tumor growth was obtained in comparison with treatment by 131I-3H11 only. CONCLUSION: The anti-VEGF antibody may be potentially useful for clinical treatment of cancer.

Animals↗

[Inhibition of in vivo growth of lung carcinoma cells after transfection with gap junction gene Cx43].

OBJECTIVE: To explore the effects of expression of gap junction gene and cell-cell communication on tumor growth. METHODS: A highly metastatic human lung carcinoma cell line PG was used. PG cells were defective of gap junctional intercellular communication(GJIC) and lacking expression of gap junction gene Cx43. By transfection, Cx43 cDNA was introduced into PG cells and blank vector cDNA was used as mock control. By using Northern-blot, dye-transfer methods and examinations of in vitro/in vivo growth, stable Cx43 transfectant cells were studied. RESULTS: The mock control cells resembled untransfected PG cells in lacking expression of Cx43 and GJIC function. They grew fast in soft agar(colony formation rate 11.6%) and in nude mice (average tumor weight 3.47 g in 28 days). The Cx43 transfectant cells showed increased level of Cx43 mRNA and increased function of GJIC. Cell growth in soft agar and in nude mice was markedly retarded. The inhibition rate was 90% and 75%, respectively. CONCLUSION: Increased expression of gap junction gene Cx43 induced tumor-suppressing effects in human lung carcinoma cells.

Animals↗

Quantitative real time measurement of iris configuration in human eyes.

PURPOSE: To evaluate intraobserver and interobserver reproducibility of real time measurement of iris morphology in living human eyes. METHODS: Based on the platform of software (Autocad, version 12), we developed an ultrasound biomicroscopy (UBM) image assistant measuring system. By using the system, we can perform the iris configuration quantitative measurement in living eyes. The measuring parameters including: iris rest length, radius of iris curvature, and the thickness in different parts of iris. Ten anterior segment images of one normal individual were obtained by a single operator to evaluate the intraobserver reproducibility of image capture, and ten times measurement of one image were performed by a single operator to assess the reproducibility of image measurement. The measurement of three independent observers were compared to investigate interobserver reproducibility in quantitative measurement. Intraobserver and interobserver reproducibility of measurement were assessed by calculating the coefficient of variation for each individual observer and by using the F test to detect a difference among observers. The iris configuration of 96 subjects (192 eyes) were measured. RESULTS: Intraobserver reproducibility was ranged from 0.9-4.9% in all measured parameters. Interobserver reproducibility for some of measured parameters varied considerably and was affected by subjective interpretative of visualized anatomic landmarks. The preliminary measured parameters in Chinese Show that iris rest length is 3.699 +/- 0.397 mm, radius of iris curvature is 9.101 +/- 1.408 mm, the average thickness of iris is 0.406 +/- 0.042 mm. CONCLUSION: The intraobserver reproducibility and the measured accuracy can fit the requisition of the ocular biometry and of the ocular physiology, pathophysiology, and pharmacology study. The method supply a new assistance for UBM image measurement.

Adult↗

[The primary study of ultrasound biomicroscope in imaging anterior segment tumors of eye].

PURPOSE: To evaluate the use of ultrasound biomicroscope (UBM) in imaging anterior segment tumors of eye. METHODS: 13 cases of anterior segment tumors of eye were examined with UBM. RESULTS: 3 cases had the ocular history of trauma or surgery and were clinically diagnosed as anterior iris cysts. UBM displayed the cysts as thin-walled, no internal reflectivity, and at the locate of anterior humour angle; 8 cases had superficial anterior humour, narrow anterior angle and clinically be suspected as tumors behind iris or ciliary body. UBM showed cystic reflectivity in 7 cases and a solid tumor in ciliary body in one case. 2 cases were clinically diagnosed as iris nevi. UBM displayed solid convex lesions. CONCLUSION: UBM is a valuable new technique in the diagnosis and accurate localization of anterior segment tumors.

Adult↗

[Application of ultrasound biomicroscopy in diagnosis of anterior segment vitreoretinal disorders].

PURPOSE: To investigate the diagnostic value of ultrasound biomicroscopy(UBM) in anterior segment vitreoretinal disorders(ASVD). METHODS: 60 eyes of 58 sequential patients were examined with UBM. The ultrasound biomicroscopic images were compared with the results of clinic examination, B-scan ultrasonography and the finding during surgery to evaluate the reliability of UBM for ASVD. RESULTS: UBM allows structural details of the conjunctiva, rectus muscle, sclera, uvea, retina and vitreous to be visualized at microscopic resolution in living eye. The area of UBM may cover from cornea to vitreous base, partially to the equator of eye. A variety of the changes of ASVD were imaged in 60 eyes, including retinal detachment in 43 eyes, retinal circumferential contraction in 29 eyes, retinal anterior displacement in 24 eyes, vitreous opacities or fibrosis in 57 eyes, ciliary orchoroidal detachment in 26 eyes, ciliary nonpigmented epithelial detachment in 6 eyes, proliferative tissue at the sclerotomy site in 9 eyes, retinal neoplasm in 2 eyes, ciliary cyst in 6 eyes, proliferation of peripheral silicone oil in 8 eyes, silicone oil emulsification in 7 eyes and vitreous foreign body in 2 eyes, respectively. CONCLUSIONS: Our studies showed the feasibility of UBM for ASVD not visible by current techniques UBM can be used for the diagnosis, differential diagnosis and the instructive treatments of ASVD.

Adult↗

Erbium:YAG laser sclerectomy with a sapphire optical fiber.

BACKGROUND AND OBJECTIVE: Laser sclerectomy may offer advantages to conventional glaucoma filtering surgery by minimizing conjunctival manipulation and subsequent subconjunctival scarring and by providing easier access to difficult locations. It has been theorized that minimizing collateral thermal damage may enhance the success rate and reduce complications associated with laser sclerectomy. The thermal damage induced by the pulsed erbium:yttrium aluminum garnet (Er:YAG) laser is notably less than that of other laser modalities, including neodymium:YAG (1.06 microns), Er:YSGG (2.79 microns), holmium: YAG (2.10 microns), and holmium: YSGG (2.10 microns). A major obstacle to the clinical use of the Er:YAG laser has been the lack of an efficient and reliable delivery system. The single-crystal sapphire optical fiber has an acceptable attenuation rate and favorable characteristics for delivery of the Er:YAG wave-length in a clinical setting. MATERIALS AND METHODS: An Er:YAG laser (2.94 microns) focused into a 300-micron, single-crystal sapphire fiber was used to create ab-externo sclerectomies with varying energy levels and pulse rates in each eye of six anesthetized rabbits and six human cadaver eyes. Specimens then underwent histopathologic analysis and determination of the thermal damage zone. RESULTS: For the rabbit sclerectomies, there was a significant positive correlation between energy per pulse and the diameter of the thermal damage zone, which averaged 22.0 +/- 12.7 microns for all energy levels. For the human sclerectomies, a positive correlation existed between the total energy delivered (mJ/pulse x total pulses) and the thermal damage zone, with the mean thermal damage zone, being 25.0 +/- 9.0 microns. CONCLUSION: The Er:YAG laser with a sapphire optical fiber delivery system is an effective means of creating ab-externo sclerectomies with minimal thermal damage.

Animals↗

Transformations to additivity in measurement error models.

In many problems, one wants to model the relationship between a response Y and a covariate X. Sometimes it is difficult, expensive, or even impossible to observe X directly, but one can instead observe a substitute variable W that is easier to obtain. By far, the most common model for the relationship between the actual covariate of interest X and the substitute W is W = X + U, where the variable U represents measurement error. This assumption of additive measurement error may be unreasonable for certain data sets. We propose a new model, namely h(W) = h(X) + U, where h(.) is a monotone transformation function selected from some family H of monotone functions. The idea of the new model is that, in the correct scale, measurement error is additive. We propose two possible transformation families H. One is based on selecting a transformation that makes the within-sample mean and standard deviation of replicated W's uncorrelated. The second is based on selecting the transformation so that the errors (U's) fit a prespecified distribution. Transformation families used are the parametric power transformations and a cubic spline family. Several data examples are presented to illustrate the methods.

Adult↗

Study on enzyme electrode biosensor of choline.

Choline oxidase was immobilized at a hydrogen peroxide electrode and the enzyme electrode was used for the amperometric determination of choline. The linear range is 0-200 mg/L with a response time of 40 seconds and a 25-microliter sample injection. The relative standard deviation (RSD) is less than 1.5% in 20 assays. The enzyme membrane can be used continuously at 25 degrees C for 60 days. The recovery rate of this method is 100.3-102.3%.

Alcohol Oxidoreductases↗