Biomedical subjects

Su Huang

Publications and source records attributed to Su Huang.

8 recordsLinked to original sources

PubMed2006

Calcium receptor stimulates chemotaxis and secretion of MCP-1 in GnRH neurons in vitro: potential impact on reduced GnRH neuron population in CaR-null mice.

The factors controlling the migration of mammalian gonadotropin-releasing hormone (GnRH) neurons from the nasal placode to the hypothalamus are not well understood. We studied whether the extracellular calcium-sensing receptor (CaR) promotes migration/chemotaxis of GnRH neurons. We demonstrated expression of CaR in GnRH neurons in the murine basal forebrain and in two GnRH neuronal cell lines: GT1-7 (hypothalamus derived) and GN11 (olfactory bulb derived). Elevated extracellular Ca(2+) concentrations promoted chemotaxis of both cell types, with a greater effect in GN11 cells. This effect was CaR mediated, as, in both cell types, overexpression of a dominant-negative CaR attenuated high Ca(2+)-stimulated chemotaxis. We also demonstrated expression of a beta-chemokine, monocyte chemoattractant protein-1 (MCP-1), and its receptor, CC motif receptor-2 (CCR2), in the hypothalamic GnRH neurons as well as in GT1-7 and GN11 cells. Exogenous MCP-1 stimulated chemotaxis of both cell lines in a dose-dependent fashion; the effect was greater in GN11 than in GT1-7 cells, consistent with the higher CCR2 mRNA levels in GN11 cells. Activating the CaR stimulated MCP-1 secretion in GT1-7 but not in GN11 cells. MCP-1 secreted in response to CaR stimulation is biologically active, as conditioned medium from GT1-7 cells treated with high Ca(2+) promoted chemotaxis of GN11 cells, and this effect was partially attenuated by a neutralizing antibody to MCP-1. Finally, in the preoptic area of anterior hypothalamus, the number of GnRH neurons was approximately 27% lower in CaR-null mice than in mice expressing the CaR gene. We conclude that the CaR may be a novel regulator of GnRH neuronal migration likely involving, in part, MCP-1.

Animals↗

PubMed2006

IVME: a tool for editing, manipulation, quantification, and labeling of cerebrovascular models.

Three-dimensional (3D) vascular models are important in medical education, interventional radiology and vascular surgery. Because of a limited quality of angiographic images and inaccuracies introduced during their processing, interactive enhancement of the resulting models is required. We introduce here a novel tool, the interactive vascular modeling environment (IVME) for editing, manipulation, quantification, and labeling of cerebrovascular models. We describe the IVME architecture and design along with the functionality supporting anatomy terminology linking, 2D and 3D labeling, editing, 2D-3D cross-referencing, measurements, and quantification. The IVME is a useful platform in education, research, and clinics to explore and manipulate the angiography data in 2D and 3D.

Cerebral Angiography↗

PubMed2006

Differential activity of kaempferol and quercetin in attenuating tumor necrosis factor receptor family signaling in bone cells.

Increasing data from epidemiological and in vitro studies show that the isoflavonoids, genistein and daidzein, and the flavonols, quercetin and kaempferol, are protective against postmenopausal bone loss. However, the physiological mechanisms for these effects are not well understood. We now report that kaempferol exerts profound antiosteoclastogenic effects by acting on both osteoblasts and osteoclasts. Kaempferol but not quercetin dose-dependently inhibited tumor necrosis factor alpha (TNFalpha)-induced production of the osteoclastogenic cytokines interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1/CCL2) in osteoblasts. The effect on IL-6 was posttranscriptional, whereas kaempferol reduced MCP-1 mRNA levels. In addition, in mouse primary calvarial osteoblasts, kaempferol but not quercetin blocked TNFalpha-induced translocation of the nuclear factor kappaB (NF-kappaB) subunit p65 from the cytoplasm to the nucleus. However, TNFalpha-stimulated intracellular ROS production was unaltered by kaempferol. In RAW264.7 cells, a monocyte/macrophage precursor for osteoclasts, both kaempferol and quercetin dose-dependently inhibited the receptor activator of NF-kappaB ligand (RANKL)-induced immediate-early oncogene c-fos expression at 6 h. After 3-5 days, both flavonols robustly inhibited RANKL-induced expression of the osteoclastic differentiation markers, RANK and calcitonin receptor. Consistent with down regulation of these osteoclastic differentiation markers, both flavonols strongly attenuated the RANKL-induced formation of multinucleated osteoclasts. However, kaempferol was more potent than quercetin in inhibiting RANKL-stimulated effects on RAW264.7 cells. Thus, our data indicate that kaempferol exerts profound antiosteoclastogenic effects by specifically antagonizing TNF receptor family action on bone cells at two distinct levels, by disrupting production of osteoclastogenic cytokines from osteoblasts and attenuating osteoclast precursor cell differentiation.

Animals↗

PubMed2006

A medical imaging and visualization toolkit in Java.

Medical imaging research and clinical applications usually require combination and integration of various techniques ranging from image processing and analysis to realistic visualization to user-friendly interaction. Researchers with different backgrounds coming from diverse areas have been using numerous types of hardware, software, and environments to obtain their results. We also observe that students often build their tools from scratch resulting in redundant work. A generic and flexible medical imaging and visualization toolkit would be helpful in medical research and educational institutes to reduce redundant development work and hence increase research efficiency. This paper presents our experience in developing a Medical Imaging and Visualization Toolkit (BIL-kit) that is a set of comprehensive libraries as well as a number of interactive tools. The BIL-kit covers a wide range of fundamental functions from image conversion and transformation, image segmentation, and analysis to geometric model generation and manipulation, all the way up to 3D visualization and interactive simulation. The toolkit design and implementation emphasize the reusability and flexibility. BIL-kit is implemented in the Java language so that it works in hybrid and dynamic research and educational environments. This also allows the toolkit to extend its usage for the development of Web-based applications. Several BIL-kit-based tools and applications are presented including image converter, image processor, general anatomy model simulator, vascular modeling environment, and volume viewer. BIL-kit is a suitable platform for researchers and students to develop visualization and simulation prototypes, and it can also be used for the development of clinical applications.

Algorithms↗

PubMed2004

Developmentally regulated role for Ras-GRFs in coupling NMDA glutamate receptors to Ras, Erk and CREB.

p140 Ras-GRF1 and p130 Ras-GRF2 constitute a family of calcium/calmodulin-regulated guanine-nucleotide exchange factors that activate the Ras GTPases. Studies on mice lacking these exchange factors revealed that both p140 Ras-GRF1 and p130 Ras-GRF2 couple NMDA glutamate receptors (NMDARs) to the activation of the Ras/Erk signaling cascade and to the maintenance of CREB transcription factor activity in cortical neurons of adult mice. Consistent with this function for Ras-GRFs and the known neuroprotective effect of CREB activity, ischemia-induced CREB activation is reduced in the brains of adult Ras-GRF knockout mice and neuronal damage is enhanced. Interestingly, in cortical neurons of neonatal animals NMDARs signal through Sos rather than Ras-GRF exchange factors, implying that Ras-GRFs endow NMDARs with functions unique to mature neurons.

Animals↗

PubMed2004

High K+ and IGF-1 protect cerebellar granule neurons via distinct signaling pathways.

In culture, cerebellar granule neurons die of apoptosis in serum-free media containing a physiologic level of K(+) but survive in a depolarizing concentration of K(+) or when insulin-like growth factor 1 (IGF-1) is added. Both Akt/PKB activation and caspase-3 inhibition were implicated as the underlying neuroprotective mechanisms. The duration of high K(+), however, induced survival effects that outlasted its transient activation of Akt, and granule neurons derived from caspase-3 knockout mice died to the same extent as did those from wild-type mice, suggesting that additional mechanisms are involved. To delineate these survival mechanisms, we compared the activities of two major survival pathways after high K(+)-induced depolarization or IGF-1 stimulation. Although IGF-1 promoted neuronal survival by activating its tyrosine kinase receptor, high K(+) depolarization provided the same effect by increasing the Ca(2+) influx through the L Ca(2+) channel. Moreover, high K(+)-induced depolarization resulted in sustained activation of MAP kinase, whereas IGF-1 activated Akt in 4 hr. Inhibition of MEK (MAP kinase kinase) by either PD98059 or UO126 abolished the protective effect of high K(+)-induced depolarization, but not that of IGF-1, suggesting that activation of the MAP kinase pathway is necessary for high K(+) neuroprotective effects. We demonstrated also that high K(+)-induced depolarization, but not IGF-1, increased phosphorylation of cAMP-response element-binding protein (CREB) and protein synthesis, both of which can be blocked by UO126. Overall, our findings suggested that high K(+)-induced depolarization, unlike IGF-1, promoted neuronal survival via activating MAP kinase, possibly by increasing CREB-dependent transcriptional activation of specific proteins that promote neuronal survival.

Animals↗

PubMed2003

Identification of antigens by monoclonal antibody PD4 and its expression in Escherichia coli.

AIM: To clone and express the antigen of monoclonal antibody (MAb) PD4 for further investigation of its function. METHODS: MGC803 cDNA expression library was constructed and screened with PD4 as probes to clone the antigen. After failed in the library screening, immunoprecipitation and SDS-polyacrylamide gel electrophoresis were applied to purify the antigen for sequence analysis. The antigen coming from Mycoplasma hyorhinis (M. hyorhinis) was further confirmed with Western blot analysis by infecting M. hyorhinis -free HeLa cells and eliminating the M. hyorhinis from MGC803 cells. The full p37 gene was cloned by PCR and expressed successfully in Escherichia coli after site-directed mutations. Immunofluorescence assay was used to demonstrate if p37 protein could directly bind to gastric tumor cell AGS. RESULTS: The cDNA library constructed with MGC803 cells was screened by MAb PD4 as probes. Unfortunately, the positive clones identified with MAb PD4 were also reacted with unrelated antibodies. Then, immunoprecipitation was performed and the purified antigen was identified to be a membrane protein of Mycoplasma hyorhinis (M. hyorhinis) by sequencing of N-terminal amino acid residues. The membrane protein was intensively verified with Western blot by eliminating M. hyorhinis from MGC803 cells and by infecting M. hyorhinis-free HeLa cells. The full p37 gene was cloned and expressed successfully in Escherichia coli after site-directed mutations. Immunofluorescence demonstrated that p37 protein could directly bind to gastric tumor cell AGS. CONCLUSION: The antigen recognized by MAb PD4 is from M. hyorhinis, which suggests the actions involved in MAb PD4 is possibly mediated by p37 protein or M. hyorhinis. As p37 protein can bind directly to tumor cells, the pathogenic role of p37 involved in tumorigenesis justifies further investigation.

Antibodies, Monoclonal↗

PubMedDate not supplied

Informatics in Radiology (infoRAD): three-dimensional atlas of the brain anatomy and vasculature.

Of the existing atlases of the brain anatomy and cerebrovasculature, none integrates the anatomy and vasculature by providing for direct manipulation of three-dimensional (3D) cerebral models. An atlas-based application was developed in four steps: (a) construction of 3D anatomic models, (b) construction of 3D vascular models, (c) interactive spatial coregistration of the anatomic and vascular models, and (d) development of functionality and a user interface for the application. Three-dimensional anatomic models were imported from an electronic brain atlas database derived from classic print atlases. A novel vascular modeling technique was developed and applied to create a vascular atlas from magnetic resonance angiographic data. The use of 3D polygonal models allows smooth navigation (rotation, zooming, panning) and interactive labeling of anatomic structures and vascular segments. This application enables the user to examine 3D anatomic structures and 3D cerebral vasculature and to gain a better understanding of the relationships between the two. The combined anatomic-vascular atlas is a user-friendly neuroeducational tool that is useful for medical students and neuroscience researchers as well as for educators in preparing teaching materials.

Brain↗