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Biomedical subjects

H Liu

Publications and source records attributed to H Liu.

At least 397 records · Page 22Linked to original sources

In vivo expression of the interleukin 4 receptor alpha by astrocytes in epilepsy cerebral cortex.

We reported previously that non-neoplastic astrocytes (derived from brain tissues of patients with epilepsy) expressed interleukin 4 receptor alpha (IL-4Ralpha) and responded to interleukin 4 (IL-4) in culture. To determine whether reactivity of cultured astrocytes was relevant to primary tissue, we investigated IL-4Ralpha expression in specimens of non-neoplastic cerebral cortex removed for surgical treatment of intractable epilepsy compared to specimens of glial tumours, which have been reported to contain IL-4Ralpha. Freshly frozen tissues from eight cases (four epilepsy, four malignant astrocytoma) were evaluated for IL-4Ralpha expression by reverse-transcriptase polymerase chain reaction (RT-PCR), Southern blotting, and double-labelled immunohistochemistry with antibodies to IL-4Ralpha and glial fibrillary acidic protein (GFAP). IL-4Ralpha mRNA was detectable in both non-neoplastic and neoplastic tissues, whereas interleukin 2 receptor gamma chain (IL-2Rgammac) mRNA was not found. By immunohistochemistry, IL-4Ralpha protein co-localized to cells displaying GFAP and astrocytic morphology in epilepsy tissues. As anticipated, IL-4Ralpha was detectable in astrocytoma, but, surprisingly, was also observed in GFAP-positive, non-neoplastic "reactive" astrocytes adjacent to tumour. Results are consistent with the concept that non-neoplastic epilepsy astrocytes express IL-4Ralpha in situ, thus confirming in vitro studies and implying IL-4 sensitivity in vivo.

Actins↗

Development of a novel trans-lentiviral vector that affords predictable safety.

Lentiviral vectors derived from human immunodeficiency virus type 1 (HIV-1) hold great promise for gene therapy. However, the possibility of generating replication-competent retrovirus (RCR) through genetic recombination raises concerns for safety. Here we describe a novel HIV-based packaging system (trans-lentiviral) that splits gag/gag-pol into two parts: One that expresses gag/gag-pro and another that expresses reverse transcriptase and integrase as fusion partners of viral protein R (Vpr). Using a sensitive assay developed to specifically detect recombinant lentiviral DNA mobilization, we demonstrated that the trans-lentiviral vector prevents the generation of recombinants that contain a functional gag-pol structure, while the lentiviral vector generates env-minus recombinant lentivirus that mobilizes recombinant genomes to other cells when pseudotyped with an exogenous envelope. Since an intact gag-pol structure is absolutely required for retroviral DNA mobilization and RCR, the trans-lentiviral vector design significantly reduces this risk. Moreover, it makes it possible to assess the risk of RCR and DNA mobilization using an in vitro assay that monitors trans-lentiviral vector stocks for the regeneration of the gag-pol structure. Therefore, the trans-lentiviral vector design will ensure the greatest predictable level of safety for the clinical application of retroviral vectors, including HIV-based vectors.

Antigens, CD34↗

An efficient geometric image distortion correction method for a biplanar planar gradient coil.

Since the spatial field non-linearity of gradient coils translates into image geometric distortion in MRI, in many applications, such as cardiac function analysis and interventional MR-based device tracking/guidance, where the precise geometric information is needed, the presence of geometric image distortion can not be simply ignored. To address the concern for geometric image distortion, we have developed and validated a general and efficient numerical technique for parameterizing the global image distortion for a bi-planar gradient coil as well as accomplishing image restoration as a post-imaging processing. This image correction methodology is based on a global distortion coordinate mapping function which can be systematically defined directly from the gradient field non-linearity in 3-dimension (3D) of a given gradient coil. The image correction was carried out in two steps: (1) map each pixel of the corrected image representation onto its distorted image according to the distortion mapping; (2) interpolate the pixel intensity in the distorted image using its neighboring points via a bi-linear interpolation procedure. The results showed clearly that the distortion correction method was robust in term of the capability of reducing image geometric distortion dramatically. Also it is shown that the magnetic field non-linearity or the image distortion of a typical bi-planar gradient coil can be adequately parameterized using a finite Taylor series expansion based on its design parameters. Furthermore, this image distortion correction method is very efficient in practice for performing 3D correction for any image orientation since a compact parameterized field expression contains non-zero terms.

Biophysical Phenomena↗

The change of interleukin-6 and tumor necrosis factor in patients with obstructive sleep apnea syndrome.

The levels of lipopolysaccharide (LPS)-induced interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) expression in culture of peripheral blood mononuclear cells (PBMC) and the plasma levels of IL-6 and TNF-alpha in the patients with obstructive sleep apnea syndrome (OSAS) were measured and the relationship between OSAS and IL-6 or TNF-alpha expression studied. Both IL-6 and TNF-alpha were detected by using ELISA in 22 patients with OSAS and 16 normal controls. The levels of LPS-induced IL-6 (787.82 +/- 151.97 pg/ml) and TNF-alpha (4165.45 +/- 1501.43 pg/ml) expression in the supernatant of the culture of PBMC and plasma level of IL-6 (50.67 +/- 4.70 pg/ml) and TNF-alpha (299.09 +/- 43.57 pg/ml) in the patients with OSAS were significantly higher than those in the normal controls (in the supernatant of the culture of PBMC: 562.69 +/- 197.54 pg/ml and 1596.25 +/- 403.08 pg/ml respectively; in the plasma; 12.69 +/- 2.75 pg/ml and 101.88 +/- 21.27 pg/ml respectively). There were significantly positive correlation between the levels of IL-6 and TNF-alpha and the percentage of time of apnea and hyponea, as well as the percentage of time spending at SaO2 below 90% in the total sleep time. It was concluded that LPS-induced IL-6 and TNF-alpha levels as well as plasma IL-6 and TNF-alpha levels in the patients with OSAS were up-regulated, which may be associated with the pathogenesis of OSAS.

Adult↗

The diagnosis value and its implication of impulse oscillometry in obstructive sleep apnea syndrome patients.

The change of measurements of impulse oscillometry (IOS) in obstructive sleep apnea syndrome (OSAS) patients and its mechanism were observed. The respiratory impedance was measured by using IOS technique and polysomnography (PSG) was monitored synchronously in 36 OSAS patients, 14 patients with chronic obstructive pulmonary disease (COPD) and 12 normal controls. Results showed that R20 in OSAS group was significantly higher than in COPD group and control group (P < 0.01). R5-R20 in OSAS group was lower than that in COPD group, but significantly higher than that in control group (P < 0.01). The levels of R20 and R5-R20 were positively correlated with severity degree of the disease. In addition, apnea-hyponea index (AHI) was positively correlated with R5 and R20 with the correlation index (r)being 0.66 and 0.86 respectively. The lowest SO2 was negatively correlated with R5 and R5-R20, with r being -0.66 and -0.79 respectively. The mean SO2 was negatively correlated with R5 and R5-R20 with r being -0.81 and -0.69 respectively. IOS technique could be used as a valuable tool for assessing the degree of upper airway obstruction in the patients with OSAS, and could help to explore its pathological mechanism.

Adult↗

Study on the relationship between plasma homocysteine and acute cerebral vascular disease.

The levels of plasma homocysteine were determined by using high-performance liquid chromatographic method. It was found that plasma homocysteine levels were significantly higher in the patients with stroke than that in the controls. There was no correlation between plasma homocysteine levels and hypertension, smoking, concentrations of blood glucose or hypertriglyceridesemia. It was suggested that hyperhomocysteinemia may be an independent risk factor for acute cerebral vascular disease.

Cerebral Hemorrhage↗

Enhanced migration of the acute promyelocytic leukemia cell line NB4 under in vitro conditions during short-term all-trans-retinoic acid treatment.

All-trans-retinoic acid (RA) is a potent differentiating agent that is very effective in the treatment of patients with acute promyelocytic leukemia (APL). Since clinical response can be accompanied by extramedullary manifestations, we have investigated the influence of RA on cell adhesion to and migration through reconstituted basement membranes (Matrigel) in the APL cell line NB4. No apparent cellular differentiation was observed during a 24-h incubation with 1 microM RA, as indicated by the nitroblue tetrazolium reduction test. However, exposure to RA significantly enhanced NB4 cell adhesion to Matrigel and consecutive migration through Matrigel barriers in a dose-dependent manner. Several integrin molecules potentially involved in this process, i.e., CD29, CD18, CD11a, CD11b and CD11c, were therefore studied by fluorescence-activated cell sorting analysis. The expression of the beta subunit of the beta2 integrins (CD18), but not that of beta1 integrins (CD29), was increased during 24-h RA treatment. Among the beta2 integrins, the expression of LFA-1 (CD11a) and of Mac-1 (CD11b), but not of p150,95 (CD11c), was induced by RA. When monoclonal antibodies that specifically block the interaction of these integrins with their ligands were used, we observed that CD29 is only involved in adhesion and CD11b only in migration, whereas CD11a participates in both processes. NB4 cells constitutively secreted the matrix metalloproteinases MMP-9 and MMP-2, which are known to promote cellular invasion processes by degradation of the extracellular matrix. RA treatment had no influence on the quantity of secreted MMP-9 or MMP-2 in these cells as determined by zymography. Addition of Batimastat (BB-94), a synthetic inhibitor of matrix metalloproteinases, blocked RA-induced cell migration without affecting cellular adhesion to Matrigel. These findings indicate that adhesion molecules as well as matrix metalloproteinases are involved in RA-stimulated migration of NB4 cells through Matrigel, possibly providing some explanation of tissue infiltration by leukemic cells as observed during treatment of APL patients with RA.

Antibodies, Monoclonal↗

Application of a modified simplex method to the multivariable optimization of a new FIA system for the determination of osmium.

A methodology based on the coupling of experimental design and a modified simplex method is proposed for the optimization of a new flow injection-kinetic system for the spectrophotometric determination of Os (IV) with m-acetylchlorophosphonazo, which has for the first time been used as chromogenic reagent in the quantitative analysis of this element. An orthogonal array design is utilized to design the experimental protocol, in which six variables are varied simultaneously, and obtain the initial simplex using 25 experiments. A modified simplex method is applied to continuously optimize the data of the orthogonal array design; the search for optimum conditions of 6 variables using the modified simplex method required only 25 experiments. The efficiency and simplicity of the coupling of the experimental design and the modified simplex method are attractive for the development of new analytical methods. The method has been applied to the determination of Os (IV) in a refined ore as well as in a secondary alloy and provided satisfactory results.

Journal Article↗

Interleukin-13 sensitivity and receptor phenotypes of human glial cell lines: non-neoplastic glia and low-grade astrocytoma differ from malignant glioma.

Many of the actions and receptor components of interleukin-13 (IL-13), a pleiotrophic cytokine with immunotherapeutic potential, are shared with IL-4. Because human low-grade astrocytoma cells express IL-4 receptors and their growth is arrested by IL-4, we speculated that IL-13 sensitivity and receptor expression might also be present. The purpose of the current study was to investigate IL-13 receptor components and sensitivity in a series of glial cell lines derived from adult human non-neoplastic cerebral cortex, low-grade astrocytoma, anaplastic astrocytoma, and glioblastoma multiforme. Unlike peripheral blood lymphocytes (PBL), glial cells did not express IL-2 receptor gamma chain. IL-13 receptor alpha-1 (IL-13Ralpha1), however, was present in 11/13 glial lines and PBL. Deficient cell lines were all glioblastoma-derived. All anaplastic astrocytoma and glioblastoma but not other glial lines or PBL expressed IL-13 receptor alpha-2 (IL-13Ralpha2). In non-neoplastic glia, low-grade, and anaplastic astrocytoma, IL-13 decreased DNA synthesis, an effect reversible with antibody to IL-4Ralpha. Results indicate that low-grade astrocytoma cells resemble non-neoplastic glia in terms of IL-13 sensitivity and IL-4Ralpha/IL-13Ralpha1 receptor profile but alterations occur with malignant progression. Glioblastoma cells were uniformly insensitive to IL-13 and, unlike other glia, failed to phosphorylate STAT6 after IL-13 challenge. Data suggest that IL-13 and analysis of IL-13 receptors may have clinical application in glial tumors.

Astrocytoma↗

Contribution of nitric oxide to the pathogenesis of cirrhotic cardiomyopathy in bile duct-ligated rats.

BACKGROUND & AIMS: Decreased cardiac contractility and beta-adrenergic responsiveness have been observed in cirrhosis, but the etiology remains unclear. We aimed to test the role of nitric oxide (NO), a negative inotropic agent, in the pathogenesis of cirrhotic cardiomyopathy in a rat model. METHODS: Cirrhosis was induced by bile duct ligation. Four weeks after ligation or sham operation, cardiac levels of tumor necrosis factor (TNF)-alpha, guanosine 3,5'-cyclic monophosphate (cGMP), inducible NOS (NOS2), and endothelial constitutive NOS (NOS3) messenger RNA (mRNA) and protein were determined. Serum nitrite/nitrate level was measured. Cardiac contractile function was evaluated in isolated left ventricular papillary muscles in the absence and presence of the NOS inhibitor nitro-L-arginine methyl ester (L-NAME). RESULTS: Cardiac TNF-alpha, NOS2 mRNA and protein, cGMP, and serum interleukin (IL)-1beta and nitrite/nitrate levels were significantly higher in cirrhotic rats than sham controls. No significant differences in NOS3 mRNA or protein were found between cirrhotic and sham control rats. Baseline isoproterenol-stimulated papillary muscle contractile force was significantly lower in the cirrhotic group; with L-NAME incubation, contractile force increased significantly in cirrhotic rats but was unaffected in the controls. In normal papillary muscles, IL-1beta attenuated the contractility, but coincubation with L-NAME again reversed this attenuation. Incubation with the exogenous NO donor S-nitroso-N-acetyl-penicillamine also blunted papillary muscle contractility. CONCLUSIONS: These results suggest that cytokine-induced stimulation of NOS2 plays a significant role in the pathogenesis of cirrhotic cardiomyopathy.

Animals↗

Computational mechanical model studies on the spontaneous emergent morphogenesis of the cultured endothelial cells.

To address questions concerning why and how the morphology of endothelial cells (ECs) forms under shear stress loading, a computational fluid dynamics (CFD) three-dimensional (3D) model of ECs simulating cell shape was designed. A full 3D non-linear CFD simulation was conducted to estimate the wall shear stress (WSS) distribution. The model cell was capable of random rotation, deformation, migration, and proliferation. Flow was computed after each update of the cell shape with infinitesimal configuration changes. After a finite interval of the flow computation, only the infinitesimal configuration changes that reduced the WSS were allowed to accumulate. As a result of the very long free-run computation experiment, starting with a sub-confluent pattern of cells, the model cells became confluent and were elongated and aligned, with a shape index (SI) very close to that reported for cells in vivo. The average WSS converged to the lowest value at the same time.

Algorithms↗

Determination of the alkaloid content in different parts of some Mahonia plants by HPCE.

The contents of three quaternary alkaloids (berberine, palmatine, jatrorrhizine) in different parts of the genus Mahonia were determined by high-performance capillary electrophoresis (HPCE). The background electrolyte system composed of 0.1 M phosphate buffer (pH 7.0)-methanol (2:1 V/V) was found to be the most suitable solution for this separation. Brucine was used as internal standard. The linear calibration ranges were 0.004986-0.4986 mg ml-1 (r = 0.9990, n = 5) for berberine, 0.005049-0.5049 mg ml-1 (r = 0.9996, n = 5) for palmatine, and 0.005058-0.5058 mg ml-1 (r = 0.9984, n = 5) for jatrorrhizine. The relative standard deviations were 1.56%, 1.02%, and 1.60% for berberine, palmatine, and jatrorrhizine (n = 6), respectively. The recoveries were determined to be 96.00-101.66% for berberine, 100.15-102.97% for palmatine, and 96.68-102.44% for jatrorrhizine. By using proposed HPCE method, three alkaloids were well-separated within only 5.0 min.

Alkaloids↗

Nine novel precursors of Buthus martensii scorpion alpha-toxin homologues.

The cDNAs encoding nine novel alpha-toxin homologues were isolated from the venom gland cDNA library of the Chinese scorpion Buthus martensii Karsch (BmK). They are rich in AAAA and TTTT elements at the 5' UTRs. The flanking region of the translation initiation codon ATG is AAAATGAA, which is highly conserved in scorpion Na(+), K(+) and Cl(-) channel toxin genes. These putative scorpion alpha-toxins shared 45.5-98.4% homology with the characterized BmK alpha-toxins, and were completely conserved in the positions of all eight cysteines. This showed, together with higher homology at nucleotide level than that at amino acid level, that these toxins may originate from a common ancestor. The discovery of a series of homologues of scorpion alpha-toxin with a different degree of natural mutation in the primary structure will provide us with a valuable system for studying the structure-function relationship of scorpion toxins.

Amino Acid Sequence↗

Patterns of status epilepticus-induced substance P expression during development.

Substance P, which modulates synaptic excitability, can be induced by a variety of stimuli. We studied the expression of hippocampal substance P in rats in using lithium-pilocarpine model of status epilepticus during development. Status epilepticus resulted in an age-specific manner of substance P expression that was anatomically distinctive in hippocampal subfields. Maximal induction of substance P immunoreactivity was seen in the CA1 region of the two-week-old rats, and progressively decreased in the three-, four-week-old rats and adults. Meanwhile, the number of substance P-immunoreactive neurons in the CA3 region and dentate granule cell layer was minimal in the two-week-old animals, but approximated the adult level in the three- and four-week-old rats. No substance P-immunoreactive axon terminals were seen in the strata pyramidale and lucidum in the CA3 region of the two-week-old rats, but they were found to progressively increase in the three-, four-week-old rats and adults. To confirm substance P expression after status epilepticus, we studied the expression of preprotachykinin-A mRNA in the hippocampus of the three-week-old rats by in situ hybridization. Two hours following injection of lithium-pilocarpine, preprotachykinin-A mRNA dramatically increased in the granule cells, as well as in the CA3 and CA1 pyramidal cell layers of the hippocampus. To evaluate the relationship between behavioral seizures and substance P induction, we used the NMDA receptor antagonist MK-801. Injection of MK-801 completely blocked lithium-pilocarpine-induced behavioral seizures and SP induction in the two-week-old rats. These results indicate that seizure activity selectively evokes age-dependent and region-selective expression of substance P.

Age Factors↗

An investigation of the impulse functions for the nonlinear BOLD response in functional MRI.

Functional MRI (fMRI) based on blood oxygenation level dependent (BOLD) contrast can be used to detect hemodynamic responses to a broad range of stimuli. It however remains unclear in what fashion the BOLD response is a linear system, and how the impulse function differs with stimulation of varying duration. To address this question, fMRI using visual stimulation with a wide range of duration (0.5-12 s) was performed in six human volunteers. A strong linear correlation was shown on the full width at half maximum (r = 0.998) of the BOLD response curves and the area under the curves (r = 0.999) to the duration of stimulation. However, comparing the errors of the measured and predicted response curves, our results showed a poorer linearity at stimuli of shorter duration. By examining the impulse functions derived from different stimuli, based on the assumption that a linear convolution relationship existed, a higher differentiation was shown in the experiments with shorter stimuli (<3 s). Compared to the area under the impulse function derived from 12 s stimulation, with that obtained from 0.5, 1, 2, 3, 4, 8 s stimuli resulted in differences of 66.2, 33.5, 15.1, 5.4, 0.9, 7.9%, respectively. This study suggests a higher degree of nonlinearity in the BOLD signal changes due to stimuli of shorter duration, in agreement with earlier work.

Brain↗