Biomedical subjects

Hong Guo

Publications and source records attributed to Hong Guo.

82 records · Page 5Linked to original sources

PubMed2002

Induction of tyrosine hydroxylase expression in rat fetal striatal precursor cells following transplantation.

Differentiation of neural stem cells into tyrosine hydroxylase (TH)-expressing cells was studied by cell transplantation into the various brain regions of rats that had received 6-hydroxydopamine lesion of the nigrostriatal pathway. Approximately 13.6-16.1% of survived precursor cells acquired neuronal-like features by expressing the neuronal marker doublecortin. Similarly, 20.7-25.7% of survived precursor cells differentiated into astrocytes following transplantation. Immunohistochemical analysis revealed that a fraction of the grafted precursor cells in the anterior part of the medial forebrain bundle (MFB), but not in the striatum and the substantia nigra of the lesioned side, showed strong TH immunoreactivity. This suggests that MFB is more permissive for induction of TH to the striatal precursor cells in vivo. The results further exemplify the potential of neural stem cells and the property of site-specific differentiation when the cells were transplanted to the dopaminergic system of the adult brain.

Animals↗

PubMed2002

Human glioma cells and undifferentiated primary astrocytes that express aberrant EAAT2 mRNA inhibit normal EAAT2 protein expression and prevent cell death.

Abnormal splicing of astroglial glutamate transporter EAAT2 mRNA has been suggested to account for the loss of EAAT2 protein in amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD). We have identified several clones of human U251 glioma cells which express varying amounts of aberrantly spliced EAAT2 mRNA; these clones do not express any detectable EAAT2 protein. When the wild-type EAAT2 cDNA was expressed in each of these clones, we found that the amount of EAAT2 protein inversely correlated with the levels of endogenous aberrant EAAT2 mRNA. We also observed that ectopic expression of normal EAAT2 protein is toxic to U251 cells as well as to undifferentiated primary astrocytes. We conclude that expression of aberrant EAAT2 mRNA may be one possible mechanism to repress normal EAAT2 protein expression. The implication of this study for the mechanisms of EAAT2 protein loss in ALS and AD is discussed.

5' Untranslated Regions↗

PubMed2002

Identification and comparative analysis of differentially expressed proteins in rat striatum following 6-hydroxydopamine lesions of the nigrostriatal pathway: up-regulation of amyloid precursor-like protein 2 expression.

During neurodegenerative processes, cascades of degeneration and subsequent regeneration are triggered. However, the molecular nature of the factors involved in the neurodegeneration of the CNS remains largely unknown. In this study, the variations of protein expression in the striatum of adult Sprague-Dawley rats following 6-hydroxydopamine lesions were investigated, in order to better understand the molecular events occurring in the denervated target tissue. The rat striatum, ipsilateral to the lesion was analysed by two-dimensional gel electrophoresis followed by matrix assisted laser desorption/ionization-time of flight mass spectrometry. Seven proteins were up-regulated (188.1-750% compared to control) in response to the lesion: amyloid precursor-like protein 2 (APLP2), kininogen, glucokinase, tropomyosin alpha chain, type brain-1 and calpactin I light chain; whilst four proteins, neural epidermal growth factor-like 2, minichromosome maintenance 6, and thyroid hormone receptor beta-2, were down-regulated (to between 36% and 59% of levels in sham-operated controls). Three proteins that did not match with available data in the SWISS-PROT protein database were also determined. Immunohistochemical analysis demonstrated colocalization of APLP2 and tyrosine hydroxylase in the nigral neurons. Moreover, reduction of APLP2-positive neurons in the substantia nigra pars compacta as well as the increases in the substantia nigra pars reticulata and in the striatum were observed. Furthermore, the conditioned medium of the Chinese hamster ovary cells over-expressing APLP2-751 (chondroitin sulphate-modified), but not APLP2-763 (nonchondroitin sulphate-modified), was able to increase the number of the tyrosine hydroxylase-positive neurons in fetal mesencephalic cultures. These results suggest that the expression of APLP2, a protein that has been thought to be associated with Alzheimer's disease, is up-regulated in the striatum following dopaminergic denervation. They also support the view that chondroitin sulphate-modified APLP2 protein may play an important role in the dopaminergic nigrostriatal system.

Adrenergic Agents↗

PubMed2002

Apomorphine induces trophic factors that support fetal rat mesencephalic dopaminergic neurons in cultures.

Apomorphine, the catechol-derived dopamine D1/D2 receptor agonist, is currently in use as an antiparkinsonian drug. It has previously been reported that apomorphine was able to elicit expression of the enzyme tyrosine hydroxylase, a marker for DA neurons, in the fetal rat cerebrocortical cultures whilst in the presence of brain-derived neurotrophic factor. The present study demonstrated that treatment of fetal rat ventral mesencephalic cultures with apomorphine caused a marked increase in the number of dopaminergic neurons. The action of apomorphine can be mimicked by dopamine receptor (D1 and D2) agonists or blocked by preincubation with D1/D2 receptor antagonists. Incubation of recipient mesencephalic cultures with the conditioned medium derived from apomorphine-stimulated donor mesencephalic cultures elicited a 3.72-fold increase in the number of TH-positive neurons. Increased mRNA expression levels of brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor were also found in the apomorphine-treated mesencephalic cells along with concomitant protein expression increases in the conditioned medium. Moreover, the trophic activity observed could be partially neutralized by antibodies against either brain-derived neurotrophic factor or glial cell line-derived neurotrophic factor. Cultured fetal striatal cells, but not hippocampal cells, also responded to apomorphine treatment. The membrane filtration studies revealed that both <30 kDa and >50 kDa fractions contained trophic activities. The latter characterization distinguishes them from most known neurotrophic factors. These results suggest that the apomorphine-modulated development of dopaminergic neurons may be mediated by activation of the dopamine receptor subtypes D1 and D2 thereby increasing the production of multiple growth factors.

Animals↗

PubMed2002

Characteristics of polymeric lambda-IgA binding to leukocytes in IgA nephropathy.

IgA nephropathy (IgAN) is characterized by predominant mesangial polymeric IgA1 (pIgA1) deposits, with increased plasma IgA1 levels. Plasma IgA levels are determined by the rate of IgA production, uptake by leukocytes, and removal by hepatocytes. Fc(alpha) receptor 1 (Fc(alpha)R1) is a candidate molecule for the regulation of IgA levels, but reports of its expression in leukocytes in IgAN are conflicting. Increased binding of endogenous IgA to circulating granulocytes and monocytes in IgAN was demonstrated in this study. Fc(alpha)R1 expression on leukocytes was increased, independently of plasma IgA levels. Fc(alpha)R1 was not saturated in leukocytes, because of internalization of IgA after uptake. Further binding of exogenous IgA isolated from individual subjects was observed with leukocytes from the same subjects. Compared with cells from control subjects, granulocytes but not monocytes from patients with IgAN exhibited a greater binding capacity for exogenous IgA, predominantly pIgA. To circumvent the possibility that endogenous IgA might alter Fc(alpha)R1 expression, granulocytes or monocytes derived from the HL-60 or U937 cell lines were used to explore the nature of IgA binding. A higher affinity for pIgA was demonstrated. Inhibition studies using unlabeled IgA, other serum proteins, or a specific Fc(alpha)R1-blocking antibody suggested binding mechanisms other than Fc(alpha)R1 for pIgA uptake by leukocytes. This study also suggested the migration and/or sequestration of "activated" leukocytes with predominant lambda-IgA in the mononuclear phagocytic system or inflammatory tissues, after the initial binding of lambda-pIgA. These immunologic abnormalities might contribute to the glomerulointerstitial injury in IgAN, in the presence of leukocytic infiltration.

Adult↗

PubMed2002

Ultrashort pulsed bessel beams and spatially induced group-velocity dispersion.

We find a new family of solutions of the nonparaxial wave equation that represents ultrashort pulsed light beam propagation in free space. The spatial and temporal parts of these pulsed beams are separable; the spatial transverse part is described by a Bessel function and remains unchanged during propagation, but the temporal profile can be arbitrary. Therefore the pulsed beam exhibits diffraction-free behavior with no transverse spreading, but the temporal part changes as if in a dispensive medium; the change is dominated by what we call spatially induced group-velocity dispersion. The analytical and numerical investigations show that the even- and odd-order spatially induced dispersions partially compensate for each other so as to give rise to pulse spreading, weakening, asymmetry, and center shift.

Journal Article↗

PubMed2002

[The clinical value of quantification of glucocorticoid receptors in peripheral blood mononuclear cells in myasthenia gravis].

OBJECTIVE: To evaluate the value of glucocorticoid receptor (GR) number in predicting the glucorticoid (GC) therapeutic efficacy. METHODS: GR number in peripheral blood mononuclear cells (PBMC) from thirty patients with myasthenia gravis (MG) was measured with (3)H-dexamethansone (DEX) radio-ligand binding assay. The efficacy of GC treatment was assessed with relative clinical score one month and six months after the treatment. Twenty-four patients with MG were monitored for GR number at different time points after GC treatment. RESULTS: The pre-treatment GR number was positively correlated with relative clinical score one month and six months after the treatment (r = 0.916 and r = 0.891, P < 0.01, respectively). The higher the pre-treatment GR number, the higher the clinical relative score and the better the efficacy of GC treatment. After GC treatment, GR number had a tendency to decline gradually. CONCLUSION: Pre-treatment GR number can be used as an adjuvant parameter for predicting GC therapeutic efficacy. GC treatment down-regulates GR.

Adolescent↗

PubMed2002

Protective effect of DNA-mediated immunization with a combination of SAG1 and IL-2 gene adjuvant against infection of Toxoplasma gondii in mice.

OBJECTIVE: To characterize the immune response induced by SAG1 encoding plasmid combined with IL-2 gene adjuvant in mice and to assess the protective effect of this vaccination against toxoplasmosis. METHODS: Mice were co-injected intramuscularly with plasmid encoding Toxoplasma gondii SAG1 plus murine IL-2 expression vector at a dose of 100 microg. Booster immunizations were employed 2 more times at 3-week interval. As controls, mice were inoculated with PBS or empty plasmid pcDNA3. Humoral and cellular responses were assayed using ELISA for the determination of Ab, Ab isotype and IFN-gamma, as well as IL-4. To detect the integration and dissemination of DNA in the injected mice, PCR and in situ hybridization were performed. All mice were then infected with highly virulent RH tachyzoites of Toxoplasma gondii intraperitoneally. RESULTS: Significant increases in specific IgG levels were observed in mice after immunization three times with SAG1 expression plasmid. With respect to the IgG isotype, co-inoculation of IL-2 expression plasmid enhanced the level of IgG2a and the production of IFN-gamma. Challenging mice by vaccinating with combined plasmids with RH tachyzoites resulted in prolonged survival. CONCLUSION: Humoral and cytokine responses elicited by SAG1 DNA immunization can be modulated by co-inoculation with IL-2 expression plasmid. The use of DNA vaccine in combination with an appropriate cytokine gene to prevent T. gondii infection warrants further investigation.

Animals↗

PubMed2002

[Hemangioblastic characteristics of fetal bone marrow-derived Flk1+ CD34- cells].

OBJECTIVE: To investigate whether fetal bone marrow stromal cells have hemangioblastic characteristics. METHODS: Human fetal bone marrow stromal cells (hfMSCs) were isolated and cultured. Immunophenotypes of hfMSCs were tested by FACS. hfMSCs seeded in the matrigel were induced with vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in vitro. Vascularization and hematopoiesis were detected with immunohistochemistry and electron microscope. RESULTS: The typical properties of this CD34- stromal cell population were that 99% cells expressed Flk1 (vascular endothelial cell growth factor receptor 2) and tube structure was formed. In the process of induction, hfMSCs could give rise to CD34+ round cells. CONCLUSIONS: We have demonstrated that fetal bone marrow stroma-derived Flk1+ CD34- cells could differentiate into vascular endothelial cells and hematopoietic cells, indicating that fetal bone marrow stroma-derived Flk1+ CD34- cells have hemangioblastic characteristics.

Antigens, CD34↗

PubMed2002

[Effects of anti-ABL tyrosine kinase intrabody on the growth of K562 cells in nude mice].

OBJECTIVE: To study the effects of anti-ABL tyrosine kinase intrabody on the growth of human chronic myelogenous leukemia (CML) cells in nude mice. METHODS: A recombinant retroviral vector MSCV-ibE-IRES-eGFP was constructed to express intracellular single-chain antibody (intrabody) against ABL tyrosine kinase domain in CML cells. K562 cells were transduced with the retrovirus, eGFP+ cells were then selected by fluorescence-activated cell sorting (FACS). The intrabody mRNA expression was determined by reverse transcription (RT)-polymerase chain reaction (PCR). BCR/ABL and c-ABL protein tyrosine kinase (PTK) activity in the cells was examined. Transduced cells and control group K562 cells were transplanted into nude mice respectively and the tumor sizes were dynamically observed. RESULTS: K562-ibE cell was obtained. Expression of the BCR/ABL and c-ABL protein tyrosine kinase activity of harvested K562-ibE cells were markedly inhibited. At 14, 21 and 28 days after cell injection, the tumor volumes of experimental mice were obviously smaller than that of control mice, about one half of the control groups (P < 0.05). CONCLUSION: The growth of K562-ibE cells was significantly inhibited in vivo. It is possible that inhibition of the BCR/ABL protein tyrosine kinase activity by the intrabody blocked BCR/ABL signal transduction pathway, promoted apoptosis and reduced tumorigenicity of K562 cells in vivo.

Animals↗