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Biomedical subjects

Jun Li

Publications and source records attributed to Jun Li.

At least 613 records · Page 34Linked to original sources

Application of the Fragments and Structure Analysis of Matrix-assisted Laser Desorption/Ionization Time-of-flight Mass Spectrometry in Peptide Sequencing.

The peptides of angiotensin II and fragment 18-39 of adrenocorticotropic hormone were determined by MALDI-TOF-MS-FAST. Main amino acid compositions and partial sequences of the peptides have been analyzed by the mass data of fragment ion peaks in the FAST spectra. The primary structures of these two peptides were identified by searching the protein databases. The research results showed that FAST is a powerful tool for determining the primary structure of peptides because of its high sensitivity, quickness and accuracy.

Journal Article↗

Windup leads to characteristics of central sensitization.

Central sensitization refers to enhanced excitability of dorsal horn neurons and is characterized by increased spontaneous activity, enlarged receptive field (RF) areas, and an increase in responses evoked by large and small caliber primary afferent fibers. Sensitization of dorsal horn neurons often occurs following tissue injury and inflammation and is believed to contribute to hyperalgesia. Windup refers to the progressive increase in the magnitude of C-fiber evoked responses of dorsal horn neurons produced by repetitive activation of C-fibers. In the present study, we tested the hypothesis that windup leads to central sensitization. Recordings were made from rat nociceptive dorsal horn neurons classed as wide dynamic range. Windup was produced by conditioning stimuli in a train of 12 electrical pulses (0.5 ms duration) applied to the RF at intensities three times the threshold for excitation of C-fibers and at a frequency of 0.5 Hz. Single electrical stimuli applied outside the RF never evoked responses except when delivered following conditioning stimulation inside the RF, indicating an expansion of the RF following windup. C-Fiber conditioning stimuli applied outside the RF also increased the response evoked by a single stimulus and increased the total number of spikes evoked by a train of electrical stimuli delivered inside the RF. Although both A- and C-fibers were activated, conditioning stimuli did not alter subsequent responses evoked by stimulation of A-fibers. Enhanced responsivity to C-fiber input following windup produced by stimulation inside the RF at a frequency of 0.5 Hz could be maintained for approximately 100 s by stimuli delivered at 0.1 Hz, a frequency that itself cannot produce windup. It is concluded that neuronal events leading to windup also produce some of the classical characteristics of central sensitization including expansion of RFs and enhanced responses to C- but not A-fiber stimulation. Thus, windup may be a useful tool to study mechanisms underlying certain characteristics of central sensitization related to C-fiber activity.

Afferent Pathways↗

Electrochemistry and Spectral Characterization of Oxidized and Reduced (TPPBr(x)())FeCl Where TPPBr(x)() Is the Dianion of beta-Brominated-Pyrrole Tetraphenylporphyrin and x Varies from 0 to 8.

The electrochemistry and spectroelectrochemistry of (TPPBr(x)())FeCl (TPPBr(x)() is the dianion of beta-brominated-pyrrole tetraphenylporphyrin and x = 0-8) were examined in PhCN containing tetra-n-butylammonium perchlorate (TBAP) as supporting electrolyte. Each compound undergoes two reversible to quasireversible one-electron oxidations and either three or four reductions within the potential limits of the solvent. The two oxidations occur at the conjugated porphyrin pi ring system, and DeltaE(1/2) between these two electrode reactions increases as the molecule becomes more distorted. The overall reduction of each compound involves the stepwise electrogeneration omicronf an iron(II), iron(I), and iron(I) pi anion radical. An equilibrium between chloride-bound and chloride-free iron(II) forms of the porphyrin is observed with association of the anionic ligand being favored for compounds with x > 5. Singly reduced (TPPBr(x)())FeCl (x = 0 to x = 6) forms both mono- and bis-CO adducts in CH(2)Cl(2). Only the mono-CO adduct is observed for (TPPBr(7))FeCl, and there is no binding at all of CO to (TPPBr(8))FeCl. The nu(CO) of both the mono- and bis-adducts increases with increase in the number of Br groups, but in a nonlinear fashion which is explained in terms of two competing effects. One is the electron-withdrawing affinity of the Br substitutents and the other the nonplanarity of the macrocycle.

Journal Article↗

Reduction of Secondary Carboxamides to Imines.

This article reports in detail on the discovery that zirconium(IV) salts of secondary amides and lactams are transformed by Cp(2)ZrHCl to N-substituted imines in one step. The method represents the first controlled reduction of amides and lactams to the corresponding imines, a transformation that is otherwise very difficult to achieve because imines are reduced more rapidly than carboxamides by most metal hydride reagents. No products of reductive cleavage of the carboxamides are observed. Efforts to replace 2 mol equiv of Cp(2)ZrHCl with simpler, less costly alternatives led to the finding that a diisobutylaluminum enolate can be substituted for the initial zirconium enolate. Such aluminum amides are smoothly reduced to the corresponding imine using Cp(2)ZrHCl in good yield. Moreover, aluminum amides are also reduced to imines using either low-valent titanium species or triethylsilane. In these alternative procedures, use of Cp(2)ZrHCl is eliminated altogether in the title transformation.

Journal Article↗

Electronic Structure and Properties of Trihalogen Cations X(3)(+) and XY(2)(+) (X, Y = F, Cl, Br, I).

Electronic structures, charge distributions, geometries, valence force constants, and vibrational frequencies of the homoatomic clusters F(3)(+), Cl(3)(+), Br(3)(+), and I(3)(+) and of the heteroatomic clusters ClF(2)(+), BrF(2)(+), IF(2)(+), BrCl(2)(+), ICl(2)(+), and IBr(2)(+) were determined. The self-consistent field approach extended by MP2-correlation energy or density-functional corrections was applied using various basis sets. It was found that d- and f-type polarization functions play a crucial role as in some other halogen compounds. The MP2 approach yields the most satisfactory results. The effect of the crystalline environment surrounding the Cl(3)(+), Br(3)(+), and I(3)(+) species is successfully simulated by a Madelung potential. Frequencies calculated in the crystal field are in reasonable agreement with the more reliable ones among the experimental results. Coupling force constants were determined. They are not consistent with some empirical rules. Bonding and charge distributions of the formally mixed-valence systems X(+)Y(2)(0) are discussed. X(+) behaves like a divalent chalcogen with high electronegativity. Each of the X(+)-Y bonds in XY(2)(+) is very similar to the bond in X-Y. We predict the experimentally unknown F(3)(+) to be stable in vacuum but not in the solid state. Structures and frequencies of XY(2)(+) species, which are as yet unknown, are also predicted.

Journal Article↗

Pharmacokinetic and pharmacodynamic of irbesartan in renal hypertensive dogs under non-steady-state and steady-state conditions.

The aim of this study was to investigate the pharmacokinetic and pharmacodynamic properties of irbesartan in renal hypertensive dogs under non-steady-state and steady-state conditions using pharmacokinetic-pharmacodynamic (PK/PD) modeling. Drugs were administered intragastrically to renal hypertensive dogs, plasma drug concentration was determined by HPLC method and Pharmacologic effects, including SBP, DBP, dp/dtmax and LVSP, were measured simultaneously. AT II, Aldosterone (ALD) and Endothelin (ET) were also used as measurement of effect. The PK and PD data were quantitatively analyzed according to the PK/PD model theory. The pharmacokinetic profiles of irbesartan conformed to a two-compartment open model. There was hysteresis loops between effects and plasma concentrations under non-steady-state condition. The relationship between effects and effect compartment concentrations (Ce) could be represented by the Sigmoid-Emax model. The Hysteresis loops disappeared under steady-state condition with more rapidly attainment of maximum concentration and effect. There were certain difference of pharmacokinetic and pharmacodynamic properties between non-steady-state and steady-state condition.

Angiotensin II Type 1 Receptor Blockers↗

Major bile duct injuries after laparoscopic cholecystectomy: a tertiary center experience.

Bile duct injury is a severe and potentially life-threatening complication of laparoscopic cholecystectomy. Several series have described a 0.5% to 1.4% incidence of bile duct injuries during laparoscopic cholecystectomy. The aim of this study was to report on an institutional experience with the management of complex bile duct injuries and outcome after surgical repair. Data were collected prospectively from 40 patients with bile duct injuries referred for surgical treatment to our center between April 1998 and December 2003. Prior to referral, 35 patients (87.5%) underwent attempts at surgical reconstruction at the primary hospital. In 77.5% of the patients, complex type E1 or type E2 BDI was found. Concomitant with bile duct injury, seven patients had vascular injuries. Roux-en-Y hepaticojejunostomy was carried out in 33 patients. In two patients, Roux-en-Y hepaticojejunostomy and vascular reconstruction were necessary. Five patients, one with primary nondiagnosed Klatskin tumor, required right hepatectomy. Two patients, both with bile duct injuries and vascular damage, died postoperatively. Because of progressive liver insufficiency, one of them was listed for high-urgency liver transplantation but died prior to intervention. At the median follow-up of 589 days, 82.5% of the patients are in excellent general condition. Seven patients have signs of chronic cholangitis. Major bile duct injuries remain a significant cause of morbidity and even death after laparoscopic cholecystectomy. Because they present a considerable surgical challenge, early referral to an experienced hepatobiliary center is recommended.

Adult↗

A survey for paralytic shellfish poisoning (PSP) in Vancouver Harbour.

Shellfish samples were collected from seven inter-tidal and two sub-tidal sites between 23 May and 8 June 1999 in Vancouver Harbour and were analysed for paralytic shellfish poisoning (PSP) using a mouse bioassay. PSP was detected in mussels collected at four sampling sites in English Bay and Burrard Inlet, at a concentration below 20 microg saxitoxin equivalents (STXeq)/100 g wet weight.

Animals↗

Poly(ester urethane)s consisting of poly[(R)-3-hydroxybutyrate] and poly(ethylene glycol) as candidate biomaterials: characterization and mechanical property study.

Poly(ester urethane)s with poly[(R)-3-hydroxybutyrate] (PHB) as the hard and hydrophobic segment and poly(ethylene glycol) (PEG) as the soft and hydrophilic segment were synthesized from telechelic hydroxylated PHB (PHB-diol) and PEG using 1,6-hexamethylene diisocyanate as a nontoxic coupling reagent. Their chemical structures and molecular characteristics were studied by gel permeation chromatography, 1H NMR, and Fourier transform infrared spectroscopy. Results of differential scanning calorimetry and X-ray diffraction indicated that the PHB segment and PEG segment in the poly(ester urethane)s formed separate crystalline phases with lower crystallinity and a lower melting point than those of their corresponding precursors, except no PHB crystalline phase was observed in those with a relatively low PHB fraction. Thermogravimetric analysis showed that the poly(ester urethane)s had better thermal stability than their precursors. The segment compositions were calculated from the two-step thermal decomposition profiles, which were in good agreement with those obtained from 1H NMR. Water contact angle measurement and water swelling analysis revealed that both surface hydrophilicity and bulk hydrophilicity of the poly(ester urethane)s were enhanced by incorporating the PEG segment into PHB polymer chains. The mechanical properties of the poly(ester urethane)s were also assessed by tensile strength measurement. It was found that the poly(ester urethane)s were ductile, while natural source PHB is brittle. Young's modulus and the stress at break increased with increasing PHB segment length or PEG segment length, whereas the strain at break increased with increasing PEG segment length or decreasing PHB segment length.

Biocompatible Materials↗

Detection of local polarity of alpha-lactalbumin by N-terminal specific labeling with a new tailor-made fluorescent probe.

To detect the local polarity such as the N-terminal domain of a protein molecule, 3-(4-chloro-6-hydrazino-1,3,5-triazinylamino)-7-(dimethylamino)-2-methylphenazine has been designed and synthesized as a polarity-sensitive fluorescent probe by using an s-triazine ring as a backbone, neutral red and hydrazine as a polarity-sensitive fluorophore, and a labeling group, respectively. The fluorescence properties of the probe have been characterized. The probe has the following features: (1) stable in various solvents; (2) the long-wavelength emission of >550 nm that can avoid the interferences of the background fluorescence shorter than 500 nm from common biomacromolecules; and (3) the maximum emission wavelength (lambda(em)) sensitive to solvent polarity only but not to pH and temperature. The hydrazino group in such a probe reacts readily with an active carbonyl produced by transamination of a protein molecule, leading to N-terminal specific attachment of the fluorophore and thereby allowing the monitoring of local polarity. With this probe, the polarity of the N-terminal domain in both native and heat-denatured alpha-lactalbumin has been first determined, which corresponds to that with a dielectric constant of about 16, and the hydrophobic core near the N-terminus is found to be conservative for heating. The present strategy may provide a general method to study the local environmental changes of a protein molecule under different denaturation conditions.

Fluorescent Dyes↗

Establishment of highly differentiated immortalized human hepatocyte line with simian virus 40 large tumor antigen for liver based cell therapy.

Acute liver failure and metabolic liver disorder animal models have demonstrated that hepatocytes transplanted into the liver or spleen survive and participate in the liver repopulation process, and recent studies have documented the usefulness of hepatocyte transplantation in humans. However, despite the promising cell therapy, there are still many restrictions, such as the shortage of donor human livers and the limited lifespan and the functional insufficiency of primary cultured hepatocytes. The immortalized and highly differentiated human hepatocyte could provide an unlimited supply of transplantable cells. In this study, we established an efficient and highly differentiated immortalized human hepatocyte line for bioartificial liver and hepatocyte transplantation research. Hepatocytes isolated from the liver of a 25 year old, brain dead male were transfected with pcDNA3.1 (-) recombinant plasmid containing the genes encoding simian virus 40 (SV40) large tumor antigen. One of the hepatocyte clones, HepLL, displayed highly differentiated liver functions with immortalized characteristics and was selected with a 700-300 microg/ml of G418 technique in 42 days. To characterize this immortalized cell line for cell therapy in the near future, HepLL cells were studied with immunohistochemistry, reverse transcription-polymerase chain reactions, immunoblotting, and tumorigenicity tests. The results revealed that HepLL cells displayed morphologic characteristics of liver parenchymal cells, secreted albumin, synthesized urea and glycogen, and expressed liver enriched functional markers, but there were no tumorigenic qualities after transplantation into severe combined immunodeficiency mice. Thus this immortalized human hepatocyte line is expected to be a useful tool for studying the functions of differentiated human hepatocyte and a promising strategy to resolve the shortages of donor organs and the limits of primary human hepatocyte for transplantation and bioartificial liver support systems.

Albumins↗

Growth and metabolism of human hepatocytes on biomodified collagen poly(lactic-co-glycolic acid) three-dimensional scaffold.

Hepatic tissue engineering offers a promising approach toward alleviating the need for donor liver, yet many challenges must be overcome including choice of scaffold, cell source, and immunologic barriers. Poly(lactic-co-glycolic acid) (PLGA) polymers are innovative biodegradable materials that have been shown to be useful as scaffolds for seeding and culturing various types of cells. In this study, a porous sponge scaffold of modified PLGA polymer with collagen was investigated for its ability to improve the growth and metabolism of human hepatocytes. We evaluated the biocompatibility of collagen-modified PLGA (C-PLGA) scaffolds with hepatocytes isolated from human liver. Cell adhesion and function (cell density, culture lifespan, albumin synthesis, urea synthesis, and ammonia elimination and diazepam clearance) were assessed during different culture periods. The number of hepatocytes cultured in C-PLGA scaffolds was higher compared with those cultured in PLGA scaffolds without collagen modification, and the lifespan of hepatocytes cultured in C-PLGA scaffolds was longer than that of cells cultured in PLGA scaffolds. Albumin and urea synthesis and ammonia elimination from attached hepatocytes were greater in C-PLGA than in PLGA scaffolds, with the exception of diazepam clearance. Collagen-modified PLGA scaffold is a promising biomaterial for hepatic tissue engineering.

Biocompatible Materials↗

Noninvasive detection of functional brain activity with near-infrared diffusing-wave spectroscopy.

We use near-infrared dynamic multiple scattering of light [diffusing-wave spectroscopy (DWS)] to detect the activation of the somato-motor cortex in 11 right-handed volunteers performing a finger opposition task separately with their right and left hands. Temporal autocorrelation functions g(1)(r,tau) of the scattered light field are measured during 100-s periods of motor task alternating with 100-s resting baseline periods. From an analysis of the experimental data with an analytical theory for g(1)(r,tau) from a three-layer geometry with optical and dynamical heterogeneity representing scalp, skull, and cortex, we obtain quantitative estimates of the diffusion coefficient in cortical regions. Consistent with earlier results, the measured cortical diffusion coefficient is found to be increased during the motor task, with a strong contralateral and a weaker ipsilateral increase consistent with the known brain hemispheric asymmetry for right-handed subjects. Our results support the interpretation of the increase of the cortical diffusion coefficient during finger opposition being due to the functional increase in cortical blood flow rate related to vasodilation.

Adult↗

Photostable luminescent nanoparticles as biological label for cell recognition of system lupus erythematosus patients.

In this article, we report a method for cell recognition of system lupus erythematosus (SLE) patients that uses photostable luminescent nanoparticles as biological labels. The luminescent silica nanoparticles are prepared with a water-in-oil microemulsion (W/O) technique. The silica network is produced by the controlled hydrolysis of tetraethylorthosilicate (TEOS) in water nanodroplets with the initiation of ammonia (NH3.H2O). A luminescent compound, tris(2,2'-bipyridyl)dichlororuthenium(II)hexahydrate [Ru(II)(bpy)3]2+, is doped inside as a luminescent signaling element, and the most appropriate dye concentration for the preparation of the nanoparticles with a size of 28 +/- 4 nm has been determined. The luminescent silica nanoparticles are covalently immobilized with goat anti-human immunoglobulin G (IgG), which can recognize SmIgG+ B lymphocytes. We have used antibody-labeled nanoparticles to recognize target SmIgG+ B lymphocytes isolated from the circulating blood of SLE patients. It has been observed that a bioassay based on fluorescent nanoparticles can identify target cells selectively and efficiently. And fluorescent nanoparticle labels also exhibit high photostability. The experiment results have shown that this cell recognition method was an effective one as further proof of the diagnosis of SLE.

2,2'-Dipyridyl↗

Global genechip profiling to identify genes responsive to p53-induced growth arrest and apoptosis in human lung carcinoma cells.

To identify critical genes that mediate p53-induced growth arrest and apoptosis at a global level, we profiled a human lung carcinoma cell model in which cells undergo growth arrest and apoptosis in a p53 and DNA damage-dependent manner. Profiling of the Affymetrix human HG-U1333 GeneChip, covering the entire human transcriptome, revealed about 3, 000 unique genes either induced or repressed during p53-induced growth arrest or apoptosis, respectively. A total of 1, 057 genes, including many well-known p53 targets, responded to both conditions. A mini apoptotic protein database was generated from 3, 033 unique apoptosis responsive genes. Analysis of this database yielded 23 proteins with a pro-apoptotic BH3 domain and three with anti-apoptotic BIR2/BIR3 domains, including well-known p53 targets: Bax, Puma, Noxa and survivin. In addition, 14 mitochondrial proteins were identified that contain a pro-apoptotic AVPI-like motif, and 15 proteins were identified that contain a DAVPI-like domain with the potential of being cleaved by caspases during apoptosis to release the AVPI motif. Many of the genes we identified with these domains do contain p53-binding sites either in the promoter or in the first three introns, suggesting a high probability of being direct p53 targets. Pathway analysis revealed that p53 might control the Wnt pathway through transcriptional regulation of some of its components. Thus, global chip profiling coupled with bioinformatics analysis is a powerful tool in identification of genes critical for p53-induced apoptosis. Further characterization of these genes will lead to a better understanding of the mechanism of p53 action and p53 regulation of other signaling pathways. It will also provide novel cancer drug targets for further validation.

Apoptosis↗

Radiography of soft tissue of the foot and ankle with diffraction enhanced imaging.

Non-calcified tissues, including tendons, ligaments, adipose tissue and cartilage, are not visible, for any practical purposes, with conventional X-ray imaging. Therefore, any pathological changes in these tissues generally necessitate detection through magnetic resonance imaging or ultrasound technology. Until recently the development of an X-ray imaging technique that could detect both bone and soft tissues seemed unrealistic. However, the introduction of diffraction enhanced X-ray imaging (DEI) which is capable of rendering images with absorption, refraction and scatter rejection qualities has allowed detection of specific soft tissues based on small differences in tissue densities. Here we show for the first time that DEI allows high contrast imaging of soft tissues, including ligaments, tendons and adipose tissue, of the human foot and ankle.

Ankle↗

Freeze-drying of mononuclear cells and whole blood of human cord blood.

The research on haematopoietic stem cells of human cord blood has become more important recently. People have concentrated on the preservation of cord blood stem cells. At present, cord blood can be preserved at ultra-low temperatures. In this study, we try to preserve cord blood and its constituents by freeze-drying. The experiments on both the mononuclear cell content and the whole blood of human cord blood were carried out respectively. The samples were frozen firstly by different cooling protocols in the presence of PVP, sucrose, and mannitol. Afterwards, they were vacuum-dried at a selected shelf temperature of -30 degree C for the main drying stage, and then vacuum-dried at 15 degree C for the second drying stage. The entire time of the freeze drying was 52 hours. Samples were stored at room temperature for 2 days prior to evaluation. Subsequently, the dried samples were suspended in an isotonic phosphate-buffered saline solution. The recovery of the cells were tested by a haemacytometer, and the highest cell numerical count recovery of MNC was 75.0 percent (SD = 4.1 percent) (P = 0.01), obtained in the protocol of 40 percent PVP + 20 percent sucrose + 10 percent Mannitol. The viability of the nucleated cells measured by PI staining and the ratio of the number of CD34+ to the number of lymphocytes (by the FITC anti-human CD34+ conjugated antibody method) were measured using a flow cytometer (FCM). The protocol of 40 percent PVP + 20 percent sucrose + 10 percent fetal bovine serum had the highest viability of 98.6 percent (SD = 0.7 percent) (P = 0.01). The highest ratio of CD34+ to lymphocytes was 1.2%, and the highest recovery of CD34+ was 68.4 percent (SD = 39.5 percent) (P = 0.05). Comparing the results of the lyophilized MNC subfraction with that of the whole blood, the lyophilization of the isolated MNC was more successful than that of whole blood.

Animals↗