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Biomedical subjects

Bin Liu

Publications and source records attributed to Bin Liu.

At least 253 records · Page 14Linked to original sources
PubMed2003

Complete primary structure and genomic organization of the mouse Col14a1 gene.

The entire mouse cDNA sequence for type XIV collagen was determined using overlapping PCR products. The 6456 nucleotide (nt) cDNA sequence contains a 5391-nt open reading frame encoding 1797 amino acid residues. The amino terminus has a 28-residue signal peptide that is followed by the mature polypeptide of 1769 amino acid residues with a calculated molecular mass of 193.2 kDa. The mouse alpha1(XIV) collagen chain is predicted to contain all the structural domains described for the polypeptide in chicken and human. These include fibronectin type III repeats, von Willebrand factor A domains, thrombospondin-N-terminal-like domains and two triple-helical domains similar to those of other collagen family members. The amino acid residue sequence of human alpha1(XIV) collagen showed an overall identity of 74% to the chicken sequence and 88% to the human sequence. The entire mouse genomic structure has been determined and is made up of 48 exons. Alternatively spliced forms of mouse type XIV, collagen were not identified corresponding to the findings for the human form.

Alternative Splicing↗
PubMed2003

Activation of epidermal growth factor receptor signals induction of nitric oxide synthase-2 in human optic nerve head astrocytes in glaucomatous optic neuropathy.

Glaucoma is an optic neuropathy that is associated with elevated intraocular pressure in most patients. We have previously demonstrated that the mechanism by which pressure damages optic nerve axons involves excessive nitric oxide generated by inducible nitric oxide synthase (NOS-2). We have now found that activation of the epidermal growth factor receptor (EGFR) induces NOS-2 in astrocytes of the human optic nerve head (ONH) in vitro and EGFR is significantly upregulated and tyrosine phosphorylated in reactive astrocytes in human glaucomatous ONHs in vivo. Furthermore, in response to elevated hydrostatic pressure, EGFR rapidly becomes phosphorylated in the nucleus. This pressure-dependent activation of EGFR is necessary for NOS-2 induction. Our results suggest that activation and nuclear localization of EGFR may be needed for induction of NOS-2 in response to elevated intraocular pressure in glaucomatous optic neuropathy. Identification of this key signaling pathway provides new therapeutic approaches to pharmacological neuroprotection for glaucoma.

Adult↗
PubMed2003

Comparison of the signal transduction pathways for the induction of gene expression of nitric oxide synthase-2 in response to two different stimuli.

Human optic nerve astrocytes induce nitric oxide synthase-2 (NOS-2) in vitro in response to cytokines (interferon-gamma/interleukin-1beta) and elevated hydrostatic pressure. Using relatively specific inhibitors, we have compared induction of NOS-2 in response to these two stimuli to determine whether the same or different signal transduction pathways participate in the responses. Using SN50 and CAGE, which inhibit the NFkappaB pathway, the induction of NOS-2 in response to both cytokines and elevated hydrostatic pressure was blocked. Using SB202190 and SB203580, which inhibit p38 mitogen-activated protein kinase, only the response to cytokines was blocked. In contrast, when inhibitors of epidermal growth factor receptor tyrosine kinase AG 82 and AG 18 were used, the induction of NOS-2 in response to pressure, but not in response to cytokines, was blocked. Signal transduction pathways presumably regulate the synthesis of NOS-2 through downstream events that induce transcription of the NOS-2 gene. Our data suggest that activation of different sites in the promoter region of the NOS-2 gene is needed for these different stimuli to induce NOS-2.

Adult↗
PubMed2003

A canine conditionally replicating adenovirus for evaluating oncolytic virotherapy in a syngeneic animal model.

Oncolytic adenoviruses, which selectively replicate in and subsequently kill cancer cells, have emerged as a promising approach for treatment of tumors resistant to other modalities. Although preclinical results have been exciting, single-agent clinical efficacy has been less impressive heretofore. The immunogenicity of adenoviruses, and consequent premature abrogation of replication, may have been a partial reason. Improving the oncolytic potency of agents has been hampered by the inability to study host-vector interactions in immune-competent systems, since human serotype adenoviruses do not productively replicate in animal tissues. Therefore, approaches such as immunomodulation, which could result in sustained replication and subsequently increased oncolysis, have not been studied. Utilizing the osteocalcin promoter for restricting the replication of a canine adenovirus to dog osteosarcoma cells, we generated and tested the first nonhuman oncolytic adenovirus. This virus effectively killed canine osteosarcoma cells in vitro and yielded a therapeutic benefit in vivo. Canine osteosarcoma is the most frequent malignant disease in large dogs, with over 8000 cases in the United States annually, and there is no curative treatment. Therefore, immunomodulation for increased oncolytic potency could be studied with clinical trials in this population. This could eventually translate into human trials.

Adenoviridae↗
PubMed2003

Enhanced therapeutic efficacy for ovarian cancer with a serotype 3 receptor-targeted oncolytic adenovirus.

Oncolytic viruses that are replication competent in tumor but not in normal cells represent a novel approach for treating neoplastic diseases. However, the oncolytic potency of replicating agents is determined directly by their capability of infecting target cells. Most adenoviruses used for gene therapy or virotherapy have been based on serotype 5 (Ad5). Unfortunately, expression of the primary receptor for Ad5 (the coxsackie-adenovirus receptor, or CAR) is highly variable on ovarian and other cancer cells. By performing genetic fiber pseudotyping, we created Ad5/3-Delta24, a conditionally replicating adenovirus that does not bind CAR but facilitates entry into and killing of ovarian cancer cells. We show replication of Ad5/3-Delta24 and subsequent oncolysis of ovarian adenocarcinoma lines. Replication was also analyzed with quantitative PCR on three-dimensional primary tumor cell spheroids purified from patient samples. Moreover, in a therapeutic orthotopic model of peritoneal carcinomatosis, dramatically enhanced survival was noted. Finally, Ad5/3-Delta24 achieved a significant antitumor effect as assessed by noninvasive, in vivo bioluminescence imaging. Therefore, the preclinical therapeutic efficacy of Ad5/3-Delta24 is improved over the respective CAR- and integrin-binding controls. Taken together with promising biodistribution and toxicity data, this approach could translate into successful clinical interventions for ovarian cancer patients.

Adenoviridae↗
PubMed2003

A genome sequence of novel SARS-CoV isolates: the genotype, GD-Ins29, leads to a hypothesis of viral transmission in South China.

We report a complete genomic sequence of rare isolates (minor genotype) of the SARS-CoV from SARS patients in Guangdong, China, where the first few cases emerged. The most striking discovery from the isolate is an extra 29-nucleotide sequence located at the nucleotide positions between 27,863 and 27,864 (referred to the complete sequence of BJ01) within an overlapped region composed of BGI-PUP5 (BGI-postulated uncharacterized protein 5) and BGI-PUP6 upstream of the N (nucleocapsid) protein. The discovery of this minor genotype, GD-Ins29, suggests a significant genetic event and differentiates it from the previously reported genotype, the dominant form among all sequenced SARS-CoV isolates. A 17-nt segment of this extra sequence is identical to a segment of the same size in two human mRNA sequences that may interfere with viral replication and transcription in the cytosol of the infected cells. It provides a new avenue for the exploration of the virus-host interaction in viral evolution, host pathogenesis, and vaccine development.

Base Sequence↗
PubMed2003

Complete genome sequences of the SARS-CoV: the BJ Group (Isolates BJ01-BJ04).

Beijing has been one of the epicenters attacked most severely by the SARS-CoV (severe acute respiratory syndrome-associated coronavirus) since the first patient was diagnosed in one of the city's hospitals. We now report complete genome sequences of the BJ Group, including four isolates (Isolates BJ01, BJ02, BJ03, and BJ04) of the SARS-CoV. It is remarkable that all members of the BJ Group share a common haplotype, consisting of seven loci that differentiate the group from other isolates published to date. Among 42 substitutions uniquely identified from the BJ group, 32 are non-synonymous changes at the amino acid level. Rooted phylogenetic trees, proposed on the basis of haplotypes and other sequence variations of SARS-CoV isolates from Canada, USA, Singapore, and China, gave rise to different paradigms but positioned the BJ Group, together with the newly discovered GD01 (GD-Ins29) in the same clade, followed by the H-U Group (from Hong Kong to USA) and the H-T Group (from Hong Kong to Toronto), leaving the SP Group (Singapore) more distant. This result appears to suggest a possible transmission path from Guangdong to Beijing/Hong Kong, then to other countries and regions.

Genome, Viral↗
PubMed2003

Intracranial tuberculoma in a liver transplant patient: first reported case and review of the literature.

A 66-year-old female who had undergone an orthotopic liver transplant two years before admission was admitted with fever and neurological symptoms of several days' duration. Following an extensive work-up, which revealed positive intracranial lesions on computed typography and magnetic resonance imaging, the patient was begun on broad spectrum antimicrobials including corticosteroids. The patient responded though the etiology of infection remained unclear. After a stereotactic biopsy was performed revealing granulomas and acid-fast bacilli, the patient was started on antituberculous medications. A review of the literature reveals that the rare occurrence of intracranial tuberculoma should be considered in an orthotopic liver transplant (OLT) patient with central nervous system pathology.

Aged↗
PubMed2003

Inhibition of K562 leukemia angiogenesis and growth by expression of antisense vascular endothelial growth factor (VEGF) sequence.

Vascular endothelial growth factor (VEGF), a major angiogenic factor, plays a key role in the growth of solid tumor. Recently, expression of VEGF and its receptors has been found on leukemic cells as well as on endothelial cells. VEGF may fulfill a fundamental role in promoting tumor angiogenesis and proliferation by stimulating both endothelial cells and leukemic cells. To investigate the role of VEGF in the angiogenesis and growth of leukemic cell, we used an antisense strategy to downregulate VEGF expression in K562 cells, a human erythroleukemia cell line. Expression of antisense-VEGF in K562 cells reduced the secretion of VEGF protein and inhibited cell survival. The proliferation and migration of human umbilical vein endothelial cells were decreased in response to the conditioned medium (CM) from K562 cells expressed antisense-VEGF, compared to CM from K562 cells transfected with vector control. Moreover, subcutaneous injection of nude mice with antisense-VEGF K562 cells inhibited tumor growth with a reduction of the density of microvessels and an increased apoptosis in those tumors, compared to vector control K562 cells. These results suggest that the efficient downregulation of the VEGF production in leukemic cells using antisense-VEGF may constitute a novel strategy of treatment in leukemia.

Cell Line, Tumor↗
PubMed2003

Role of microglia in inflammation-mediated neurodegenerative diseases: mechanisms and strategies for therapeutic intervention.

Evidence from postmortem analysis implicates the involvement of microglia in the neurodegenerative process of several degenerative neurological diseases, including Alzheimer's disease and Parkinson's disease. It remains to be determined, however, whether microglial activation plays a role in the initiation stage of disease progression or occurs merely as a response to neuronal death. Activated microglia secrete a variety of proinflammatory and neurotoxic factors that are believed to induce and/or exacerbate neurodegeneration. In this article, we summarize recent advances on the study of the role of microglia based on findings from animal and cell culture models in the pathogenesis of neurodegenerative diseases, with particular emphasis on Parkinson's disease. In addition, we also discuss novel approaches to potential therapeutic strategies.

Animals↗
PubMed2003

Dextromethorphan protects dopaminergic neurons against inflammation-mediated degeneration through inhibition of microglial activation.

Inflammation in the brain has increasingly been recognized to play an important role in the pathogenesis of several neurodegenerative disorders, including Parkinson's disease and Alzheimer's disease. Inflammation-mediated neurodegeneration involves activation of the brain's resident immune cells, the microglia, which produce proinflammatory and neurotoxic factors, including cytokines, reactive oxygen intermediates, nitric oxide, and eicosanoids that impact on neurons to induce neurodegeneration. Hence, identification of compounds that prevent microglial activation may be highly desirable in the search for therapeutic agents for inflammation-mediated neurodegenerative diseases. In this study, we report that dextromethorphan (DM), an ingredient widely used in antitussive remedies, reduced the inflammation-mediated degeneration of dopaminergic neurons through inhibition of microglial activation. Pretreatment (30 min) of rat mesencephalic neuron-glia cultures with DM (1-10 micro M) reduced, in a dose-dependent manner, the microglia-mediated degeneration of dopaminergic neurons induced by lipopolysaccharide (LPS, 10 ng/ml). Significant neuroprotection by DM was also evident when DM was applied to cultures up to 60 min after the addition of LPS. The neuroprotective effect of DM was attributed to inhibition of LPS-stimulated microglial activation because DM significantly inhibited the LPS-induced production of tumor necrosis factor-alpha, nitric oxide, and superoxide free radicals. This conclusion was further supported by the finding that DM failed to prevent 1-methyl-4-phenylpyridinium- or beta-amyloid peptide (1-42)-induced dopaminergic neurotoxicity in neuron-enriched cultures. In addition, because LPS did not produce any significant increase in the release of excitatory amino acids from neuron-glia cultures and N-methyl-D-aspartate antagonist dizocilpine maleate failed to afford significant neuroprotection, it is unlikely that the neuroprotective effect of DM is mediated through N-methyl-D-aspartate receptors. These results suggest that DM may be a promising therapeutic agent for the treatment of Parkinson's disease.

1-Methyl-4-phenylpyridinium↗
PubMed2003

Glaucomatous optic neuropathy: when glia misbehave.

The loss of vision in the human eye disease, glaucoma, is due to degeneration of the axons of the retinal ganglion cells. In glaucoma, reactive astrocytes in the optic nerve head contain inducible nitric oxide synthase, which apparently produces excessive nitric oxide that damages the axons. The astrocytes respond to the elevated intraocular pressure that is characteristic of the disease. An important signal transduction pathway for the induction of nitric oxide synthase in response to pressure is the epidermal growth factor receptor tyrosine kinase. Pharmacological inhibition of the activity or the induction of inducible nitric oxide synthase may provide neuroprotection for the treatment of glaucoma.

Animals↗
PubMed2003

Effect of Bak Foong pills on enhancing dopamine release from the amygdala of female rats.

To investigate whether Bak Foong Pills (BFP), a well-known gynaecological tonic, has a direct effect on the central nervous system, we employed the in vivo electrochemical detection technique, fast cyclic voltammetry (FCV), to measure the dopamine release from the mesolimbic structure-amygdala of both male and female rats. The results showed that intracerebroventricular BFP (0.75, 1.5 microg) treatment promoted dopamine release from the amygdala in both female and ovariectomized female rats. The BFP-induced response appeared within 5 min after addition of BFP and lasted for at least 40 min. However, no effect of BFP was observed in male rats for an observed period of up to 60 min. The results suggest that BFP may have gender-specific beneficial effect on dopaminergic functions of the amygdala.

Amygdala↗
PubMed2003

Parkinson's disease and exposure to infectious agents and pesticides and the occurrence of brain injuries: role of neuroinflammation.

Idiopathic Parkinson's disease (PD) is a devastating movement disorder characterized by selective degeneration of the nigrostriatal dopaminergic pathway. Neurodegeneration usually starts in the fifth decade of life and progresses over 5-10 years before reaching the fully symptomatic disease state. Despite decades of intense research, the etiology of sporadic PD and the mechanism underlying the selective neuronal loss remain unknown. However, the late onset and slow-progressing nature of the disease has prompted the consideration of environmental exposure to agrochemicals, including pesticides, as a risk factor. Moreover, increasing evidence suggests that early-life occurrence of inflammation in the brain, as a consequence of either brain injury or exposure to infectious agents, may play a role in the pathogenesis of PD. Most important, there may be a self-propelling cycle of inflammatory process involving brain immune cells (microglia and astrocytes) that drives the slow yet progressive neurodegenerative process. Deciphering the molecular and cellular mechanisms governing those intricate interactions would significantly advance our understanding of the etiology and pathogenesis of PD and aid the development of therapeutic strategies for the treatment of the disease.

Age of Onset↗
PubMed2003

Detection of target nucleic acids and proteins by amplification of circularizable probes.

Circularizable oligonucleotide probe (C-probe) is a unique molecule that offers significant advantages over conventional probes. Closed circular structure can be formed through ligation of its ends after hybridizing onto a target and locked on its target due to the helical turns formed between the complementary sequences of the target and the C-probe (padlock probe). Under an isothermal condition, C-probe can be amplified by rolling circle amplification, to generate multimeric single-stranded DNA. This multimeric single-stranded DNA can be further amplified by a ramification mechanism through primer extension and upstream DNA displacement, resulting in an exponential amplification. Usually, an unbiased product is generated by either rolling circle amplification or ramification mechanism due to the generic primers of C-probe and is localized on targets. These advantages make C-probe amplification very useful for research and molecular diagnosis, especially in the areas where other techniques are not adequately helpful. The development of C-probe-based technologies iniates a new future for molecular diagnostics. The applications of C-probe, rolling circle amplification, ramification mechanism, in situ detection, microarray, immunoassay, single nucleotide polymorphism and whole genome amplification are discussed.

Biotechnology↗