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Biomedical subjects

Hua Li

Publications and source records attributed to Hua Li.

At least 127 records · Page 7Linked to original sources

[The clinical characteristics and its relationship with metabolic syndrome in elderly subjects with impaired glucose regulation].

OBJECTIVE: To study the clinical characteristics of impaired glucose regulation (IGR) in elderly subjects and its relationship with metabolic syndrome (MS). METHODS: The exploration of IGR in 2 810 Chongqing citizens over 40 years old was done by OGTT in a cross-section study. Normal glucose tolerance (NGT), IGR and diabetes (DM) were grouped based on the1999 diagnosis standard of WHO. IGR was composed of impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and both of which. RESULTS: The prevalence of IGR was 18.11%, among which IGT (85.27%). Compared with the NGT group, the IGR group had higher age, body mass index (BMI), blood pressure, triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-c) and HOMA-IR, lower high density lipoprotein cholesterol (HDL-c) and HOMA-B. The IGR group had lower blood pressure, TG and HOMA-IR, and higher HOMA-B than the DM group. When each subgroup of IGR was compared with each other, both IFG plus IGT subgroup and IFG subgroup had higher BMI and HOMA-IR, and lower HOMA-B than IGT subgroup. The prevalences of hypertension, lipid disorder, obesity/overweight, and microalbuminuria in each subgroup of IGR were statistically higher than that of the NGT group. The prevalence of MS in the IFG plus IGT subgroup was higher than that of the IGT subgroup. CONCLUSIONS: The incidence of IGR was high in elderly people over 40 years old in local district of Chongqing city. There were various metabolic disorders in the subgroups of IGR. The IFG plus IGT and IFG group had higher BMI, hypertension, microalbuminuria and HOMA-IR, but lower HOMA-B than the IGT group.

Aged↗

Infection of porcine reproductive and respiratory syndrome virus suppresses the antibody response to classical swine fever virus vaccination.

The effects of porcine reproductive and respiratory syndrome virus (PRRSV) infection on the antibody response to vaccination with classical swine fever (CSF) vaccine in piglets were investigated. Piglets were inoculated intranasally with the PRRSV BJ-4 strain, and then vaccinated intramuscularly with CSF vaccine 2 days later. Control animals were either vaccinated with CSF vaccine or infected with PRRSV alone. Time course of the antibody response against either PRRSV or CSF vaccine was measured. In animals infected with PRRSV prior to CSF vaccination, the antibody response to CSF vaccine was significantly lower than that observed in animals treated with CSF vaccination alone, especially during 3-5 weeks after vaccination. At the same time, no significant difference in serum PRRSV antibody level was observed between the animals treated with both PRRSV and CSF vaccine and the animals treated with PRRSV alone. These results suggested that the reduced antibody response against CSF vaccine observed in PRRSV-infected animals might be related to the higher prevalence of CSF in PRRSV prevalent farms in China.

Animals↗

Determination of amino acid neurotransmitters in cerebral cortex of rats administered with baicalin prior to cerebral ischemia by capillary electrophoresis-laser-induced fluorescence detection.

An efficient, sensitive and rapid analysis of the amino acid neurotransmitters in the cerebral cortex of rats was developed by capillary electrophoresis with laser-induced fluorescence detection and fluorescein isothiocyanate (FITC) derivatization. This method was used to investigate the pharmacological effect of baicalin during cerebral ischemia. Different parameters which influenced derivatization and separation were optimized. The separation of amino acids was carried out in an uncoated fused-silica capillary (57 cm x 75 microm I.D.) with a buffer of 15 mM borate at pH 9.2 and an applied voltage of 17.5 kV. The detection limits for six amino acids were in the range of 2.1 x 10(-11)-6.3 x 10(-10) M. The changes in the level of amino acid neurotransmitters in brain cortex of three experimental rat groups were studied by this capillary electrophoresis-laser-induced fluorescence detection method. The results show that cerebral ischemia can cause a significant elevation in the concentrations of Glu, Asp, GABA, and Gly in cerebral cortex. Baicalin administration can attenuate the elevations of Glu and Asp induced by cerebral ischemia. This research demonstrates that baicalin may act as a neuroprotectant during cerebral ischemia.

Amino Acids↗

In vivo and in vitro peripheral-type benzodiazepine receptor polymerization: functional significance in drug ligand and cholesterol binding.

Peripheral-type benzodiazepine receptor (PBR) is an 18 kDa high-affinity drug ligand and cholesterol binding protein involved in various cell functions. Antisera for distinct PBR areas identified immunoreactive proteins of 18, 40, and 56 kDa and occasionally 72, 90, and 110 kDa in testicular Leydig and breast cancer cells. These sizes may correspond to PBR polymers and correlated to the levels of reactive oxygen species. Treatment of Leydig cells with human chorionic gonadotropin rapidly induced free radical, PBR polymer, and steroid formation. UV photoirradiation generates ROS species, which increased the size of intramembraneous particles of recombinant PBR reconstituted into proteoliposomes consistent with polymer formation, determined both by SDS-PAGE and by freeze-fracture electron microscopy. Spectroscopic analysis revealed the formation of dityrosines as the covalent cross-linker between PBR monomers. Moreover, photoirradiation increased PK 11195 drug ligand binding and reduced cholesterol binding capacity of proteoliposomes. Further addition of PK 11195 drug ligand to polymers increased the rate of cholesterol binding. These data indicate that reactive oxygen species induce in vivo and in vitro the formation of covalent PBR polymers. We propose that the PBR polymer might be the functional unit responsible for ligand-activated cholesterol binding and that PBR polymerization is a dynamic process modulating the function of this receptor in cholesterol transport and other cell-specific PBR-mediated functions.

Animals↗

Nonlethal conditioning for the induction of allogeneic chimerism and tolerance to islet allografts.

BACKGROUND: We reported that tolerance to skin grafts can be achieved by chimerism induction by way of nonlethal conditioning. In the present study, we evaluated the outcome of islet allografts implanted either simultaneously or after donor bone marrow cell (BMC) infusion when nonlethal conditioning was used. METHODS AND RESULTS: B10 (H-2b) mice were conditioned with antilymphocyte serum (ALS), 100 cGy total body irradiation (TBI), and given 30 x 10(6) allogeneic (B10.BR, H-2k) BMC on day 0. On day 2, cyclophosphamide was given intraperitoneally (IP), followed by a second BMC infusion on day 3. After chimeras were typed for allogeneic BMC engraftment on day 28, animals were rendered diabetic chemically and transplanted under the kidney capsule with islet allografts genetically matched or disparate to the BM. Donor-specific islet grafts were accepted (median survival time [MST] > 180 days, n=6), whereas all major histocompatibility complex (MHC)-disparate third-party BALB/c (H-2d) islet grafts were rejected (MST=13.8 days, n=4). When B10.BR BMC and islets were given simultaneously, graft acceptance (MST >140 days, n=4) was observed. Surprisingly, when MHC-disparate third-party islets (BALB/c) were given together with B10.BR BMC, long-term survival was also observed (MST >100 days, n=3). These findings suggested that conditioning alone at the time of islet implant might induce long-term engraftment without further treatment. However, only chimeric animals accepted a second-set donor-specific graft, whereas all other groups rejected it. CONCLUSION: Our data indicates that stable allogeneic chimerism and islet indefinite survival can be achieved by the use of a nonmyeloablative protocol. The results of the conditioning-only experiments are consistent with the possibility of graft accommodation.

Animals↗

N-terminus of M2 protein could induce antibodies with inhibitory activity against influenza virus replication.

New influenza vaccines have been designed based on the fact that the extracellular domain of M2 protein (M2e) is nearly invariant in all influenza A strains. To clarify which exact region of M2e could induce antibodies with inhibitory activities against influenza virus replication, four overlapping peptides covering M2e were synthesized and then coupled to the carrier protein bovine serum albumin through the cysteine of the peptides. After a vaccination course, all these four peptide vaccines could induce high levels of rabbit antibodies with predefined peptide specificity (antibody dilution: 1:6400-1:25600). Besides, the anti-N-terminal antibodies (AS2) reacted strongly with M2e, and reacted weakly with the middle part and C-terminus of M2e. The MDCK assay for cytopathic effect proved that antibodies recognizing the N-terminus of M2e could obviously inhibit replication of influenza A virus (A/wuhan/359/95) and influenza B virus (B/wuhan/321/99) in vitro in a dose-dependent manner, while antibodies recognizing the middle part and the C-terminus of M2e did not show such significant inhibitory activities. Sequence analysis indicates that the first nine N-terminal amino acid residues of M2e are extremely conservative. Just this region containing the first nine amino acid residues could induce antibodies with inhibitory activity against influenza A and influenza B virus replication, suggesting that the N-terminus of M2e may contain an epitope that could induce inhibitory antibodies against influenza virus replication in vitro.

Amino Acid Sequence↗

Quantification of analytes in overlapping peaks from capillary electrophoresis using multivariate curve resolution-alternating least squares methods.

Application of multivariate curve resolution with alternating least squares (ALS) methods to second-order data from capillary electrophoresis diode array detector (CE-DAD) is shown. Second-order data are easily obtained by setting individual data matrix of CE run one in top of the other. Initial qualitative solutions obtained by evolving factor analysis can be further optimized by simultaneous analysis of multiple electrophoresis run data with ALS regression. Quantification is achieved by the comparison of the analyte peak areas with that of pure standards. During the ALS regression procedure, the following constraints were applied: (i) both concentrations and unit pure spectra of the resolved components must be positive; (ii) elution profiles have an unimodal shape; (iii) correspondence exists between common species in the different data matrices; (iv) the pure spectrum of each species is the same in all runs where it is present. The above methods were applied for the determination of dinitrotoluene (DNT) isomeric compounds in overlapping peaks from CE.

Dinitrobenzenes↗

Quantitative chiral analysis in capillary electrophoresis from unresolved peaks using derivative electropherograms, experimental design, and artificial neural networks.

Quantitative capillary electrophoretic analysis of chiral compounds might be difficult or even impossible when baseline separation is not reached. In this work, the use of n-th derivative of the electropherogram was studied and examined on model and experimental data. The electropherograms should be first smoothed using Savitzky-Golay method and the quantitative analysis is then possible using either a graphical method or multivariate calibration applying a combination of experimental design (ED) and artificial neural networks (ANNs). The best results were obtained for the first derivative, higher derivatives are not suitable because of noise accumulation. The method was applied to real experimental data to quantify chiral amino acids from unresolved peaks, but it is applicable for quantitative analysis of any other chiral analytes from poorly resolved peaks. Precision of analysis from partially resolved peaks reached was about +/- 3.2% relative standard deviation.

Amino Acids↗

PAP7, a PBR/PKA-RIalpha-associated protein: a new element in the relay of the hormonal induction of steroidogenesis.

The precise mechanism by which the hormone-induced minimal cAMP levels act at the mitochondria to activate cholesterol transport and steroid synthesis is unknown. We propose that this mechanism involves a macromolecular signaling complex where a newly identified peripheral-type benzodiazepine receptor (PBR)-associated protein (PAP7) binds the regulatory subunit RIalpha of the cAMP-dependent protein kinase A (PKA), thus allowing for local efficient catalytic activation and phosphorylation of the substrate steroidogenesis acute regulatory protein (StAR), leading to cholesterol transfer from the low affinity StAR to the high affinity PBR cholesterol binding protein. The mouse and human PAP7 proteins were cloned, their genomic organization and chromosomal localization characterized, their tissue distribution evaluated and subcellular localization defined. PAP7 is highly expressed in steroidogenic tissues, where it follows the pattern of PKA-RIalpha expression and data from a human adrenal disease suggest that it participates in PKA-RIalpha-mediated tumorigenesis and hormone-independent hypercortisolism. PAP7 is localized in the Golgi and mitochondria and inhibition of PAP7 expression results in reduced hormone-induced cholesterol transport into mitochondria and decreased steroid formation. Taken together, these data suggest that PAP7 functions as an A-kinase anchoring protein (AKAP) critical in the cAMP-dependent steroid formation.

Adaptor Proteins, Signal Transducing↗

Long-term expression of angiostatin suppresses metastatic liver cancer in mice.

Metastatic liver cancer has a very poor prognosis and lacks effective therapy. Anti-angiogenic therapies, which starve tumors of blood supply, have proven to be effective in preclinical models because tumor growth is angiogenesis dependent. However, long-term, high-level, and sustained expression of angiogenesis inhibitors, such as angiostatin, is necessary to prevent dormant tumors from becoming active again. To achieve this objective, we engineered a recombinant adeno-associated virus (AAV) vector encoding mouse angiostatin, an endogenous inhibitor of tumor vascularization. After intraportal delivery of this vector, high-level, stable transgene expression of angiostatin lasting for at least 6 months was observed locally in hepatocytes. Gene transfer of AAV-angiostatin via the portal vein led to significant suppression of the growth of both nodular and metastatic EL-4 lymphoma tumors established in the liver and prolonged the survival time of the mice. The growth of neovessels was inhibited significantly, and extensive apoptosis of tumor cells was observed. The anti-angiogenic activity of angiostatin was independent of vascular endothelial growth factor (VEGF). The AAV-angiostatin viruses did not appear to be toxic to mice, and there was no detectable apoptosis of hepatocytes. In conclusion, these encouraging results warrant future investigation of the use of AAV-mediated anti-angiogenic gene therapy for targeting unresectable liver metastases, especially after surgical removal of primary tumors.

Angiogenesis Inhibitors↗

Recombinant protein comprising multi-neutralizing epitopes induced high titer of antibodies against influenza A virus.

In previous studies, we suggested that epitope-vaccine might be a new strategy against virus infection. Based on this hypothesis, we designed and expressed a recombinant immunogen (multi-epitope-peptide) comprising repeats of three neutralizing-epitopes (neutralizing epitopes: aa92-105, 127-133 and 183-195) of hemagglutininin (HA) of influenza virus (H3N2) in E. coli. After vaccination, the recombinant multi-epitope protein could induce a high level of antibodies with predefined multi-epitope-specificity in mice and rabbits. The epitope-specific antibodies in sera were tested using three different epitope-peptides (synthetic peptides) in ELISA assay, and the serum dilutions from 1 : 6400 to 1 : 25600 were confirmed. In western blot analysis, both the antiserum and the antibodies purified by synthetic epitope-peptide coupled sepharose columns could recognize natural HA from influenza virus particles (strain A/Wuhan/359/95 H3N2). In hemagglutination inhibition (HI) tests, these three antisera at the dilutions from 1 : 20 to 1 : 80 showed inhibitory activity. Interestingly, antisera and purified antibodies induced by the epitope-vaccine could partially inhibit plaque-formation of influenza virus (strain A/Wuhan/359/95) on MDCK cell monolayers. These results suggest that the recombinant multi-epitope vaccine can simultaneously induce multi-antiviral activities against influenza virus, which may provide a new way to develop effective vaccines against influenza virus.

Animals↗

Pressure-induced unfolding of the molten globule of all-Ala alpha-lactalbumin.

Pressure-induced unfolding of a molten globule (MG) was studied in a residue-specific manner with (1)H-(15)N two-dimensional NMR spectroscopy using a variant of human alpha-lactalbumin (alpha-LA), in which all eight cysteines had been replaced with alanines (all-Ala alpha-LA). The NMR spectrum underwent a series of changes from 30 to 2000 bar at 20 degrees C and from -18 degrees C to 36 degrees C at 2000 bar, showing a highly heterogeneous unfolding pattern according to the secondary structural elements of the native structure. Unfolding began in the loop part of the beta-domain, and then extended to the remainder of the beta-domain, after which the alpha-domain began to unfold. Within the alpha-domain, the pressure stability decreased in the order: D-helix approximately 3(10)-helix > C-helix approximately B-helix > A-helix. The D-helix, C-terminal 3(10)-helix and a large part of B- and C-helices did not unfold at 2000 bar, even at 36 degrees C or at -18 degrees C. The results verify that the MG state consists of a mixture of variously unfolded conformers from the mostly folded to the nearly totally unfolded that differ in stability and partial molar volume. Not only heat but also cold denaturation was observed, supporting the view that the MG state is stabilized by hydrophobic interactions.

Alanine↗

Constitutive model development and micro-structural topology optimisation for nafion hydrogel membranes with ionic clustering.

The deployment of electroactive ionic polymer hydrogel-metal composites in artificial muscle and BioMEMS applications has recently been intensively investigated. In order to analyse their electromechanical responses to externally applied electrical fields, it is critical to develop a constitutive model linking the macro-mechanical moduli with the micro-mechanical characteristics, and to determine the geometric size and shape of the micro-structural cluster and investigate the effect of cluster morphology on the effective electro-elastic moduli of the polymer hydrogels. As a typical ionic polymer-based hydrogel, the Nafion membrane is studied in this work. Based on the Biot poroelasticity theory, a multi-scale constitutive model which includes both macro and micro characteristics is developed using an asymptotic homogenisation method. The effect of water-volume fraction on the effective elastic moduli of the hydrogel membrane is examined for different equivalent weights. Numerical investigations show that the simulated effective constitutive moduli agree well with experimental data. The presently developed constitutive model is thus validated. In order to determine the micro-structural shape of the polymer skeleton subject to fluid pressure, a representative volume element (RVE) is designed by topology optimisation of the periodic microstructures of the Nafion hydrogels, through the minimisation of the electro-elastic interaction energy between the polymer-based fluorocarbon matrix and the surrounding fluid. This optimal RVE correctly predicts the geometric shapes of the clusters.

Compressive Strength↗

A study on additional early physiotherapy after stroke and factors affecting functional recovery.

OBJECTIVE: To investigate whether additional early physiotherapy after stroke improved functional recovery in stroke patients. DESIGN: A prospective, randomized, controlled study. SETTING: One stroke ward and an acute stroke unit in a large teaching hospital, southern China. SUBJECTS: Patients with first-onset stroke consecutively admitted to the stroke centre. INTERVENTIONS: One group (n = 78) received additional early physiotherapy (AEP) for 45 minutes, five days a week for four weeks starting within the first week since stroke onset; the routine therapy (RT) group (n = 78) received no professional rehabilitation therapy. MAIN OUTCOME MEASURES: Glasgow Coma Scale, Mini-Mental State Examination, Fugl-Meyer Assessment of Motor Recovery, Clinical Neurological Deficit Scale and Modified Barthel Index (MBI). RESULTS: Patients from the AEP group had a high drop-out rate (n = 28), but those remaining made relatively better functional recovery at 30 days than those from the RT group if measured by MBI. Multiple linear regression analysis revealed that cognitive disturbance, aphasia, double incontinence, site of lesion and sensory impairment might affect functional recovery after stroke. CONCLUSIONS: Additional early physiotherapy might improve independence of patients after stroke but failed to show benefit in other aspects in our study. Cognitive disturbance, aphasia, double incontinence, site of lesion as well as sensory impairment might affect functional outcome after stroke.

Aged↗

Diabetes gene therapy: potential and challenges.

Gene therapy, developing rapidly as a result of advances in molecular biology and the Human Genome Project, is now highlighted as a most hopeful technology of the 21st century. The major goal of gene therapy in diabetes mellitus (DM) is to maintain euglycemia in face of wide variations in dietary intake. Although some obstacles remain to be overcome, the risk-benefit ratio of gene therapy in DM is better than that of lifelong injections of insulin, and islet transplantation, which faces the problems of donor shortage and rejection. This review focuses on the recent advances in gene therapy of insulin-requiring diabetes, with particular emphasis on 1. the gene delivery systems by viral vectors, since most gene therapy approaches for DM involve the use of viral vectors, paying special attention to current efforts to overcome the disadvantages of adenovirus, adenovirus-associated virus and retrovirus vectors and targeting gene delivery for optimal efficiency of gene expression; 2. coupling the synthesis and release of the transgene insulin to serum glucose concentrations, especially with reference to the current promoters controlling at transcriptional level the ectopic insulin expression in autologous hepatocytes; 3. beta-cell replacement strategies: engineering of beta-cells, especially those derived from pluripotent stem cells, non beta-cells, and on a new comer, the K cells. Recent advances in the use of stem cells for potential application in diabetes gene therapy are also discussed.

Adenoviridae↗

[Research report of experimental database establishment of digitized virtual Chinese No.1 female].

OBJECTIVE: To establish digitized virtual Chinese No.1 female (VCH-F1) image database. METHODS: A 19 years old female cadaver was scanned by CT, MRI, and perfused with red filling material through formal artery before freezing and em- bedding. The whole body was cut by JZ1500A vertical milling machine with a 0.2 mm inter-spacing. All the images was produced by Fuji FinePix S2 Pro camera. RESULTS: The body index of VCH-F1 was 94%. We cut 8 556 sections of the whole body, and each image was 17.5 MB in size and the whole database reached 149.7 GB. We have totally 6 versions of the database for different applications. CONCLUSIONS: Compared with other databases, VCH-F1 has good representation of the Chinese body shape, colorful filling material in blood vessels providing enough information for future registration and segmentation. Vertical embedding and cutting helped to retain normal human physiological posture, and the image quality and operation efficiency were improved by using various techniques such as one-time freezing and fixation, double-temperature icehouse, large-diameter milling disc and whole body cutting.

Anatomy, Cross-Sectional↗