Lok Ting Lau

Peking University, Beijing, Beijing Shi, China

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Publications (34)203.02 Total impact

  • Article: Significance of a single-nucleotide primer mismatch in hepatitis B virus real-time PCR diagnostic assays.
    Journal of clinical microbiology 12/2011; 49(12):4418-9; author reply 4420. · 4.16 Impact Factor
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    Article: A new specialization in astrocytes: glutamate- and ammonia-induced nuclear size changes.
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    ABSTRACT: We observed nuclear swelling in glutamate (Glu)-treated astrocytes that was concomitant with but independent of astrocytic cell swelling. We confirmed Glu-induced nuclear swelling with nuclei isolated from astrocytes. Ammonia is metabolically related to Glu and could induce a nuclear swelling in intact astrocytes but shrinkage in isolated nuclei. Other compounds such as glutamine, aspartate, taurine, glycine, and ATP did not cause any nuclear swelling in isolated nuclei of astrocytes. Surprisingly, Glu and ammonia did not induce nuclear swelling in microglia, C6, HEK 293, or Hep G2 cell lines in cultures and their isolated nuclei. The Glu- and ammonia-induced nuclear size changes appear to be a specific response of astrocytes to these two closely related metabolic compounds.
    Journal of Neuroscience Research 05/2011; 89(12):2041-51. · 2.74 Impact Factor
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    Article: Development of multiplex nucleic acid sequence-based amplification for detection of human respiratory tract viruses.
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    ABSTRACT: A group of common lower respiratory tract infections, influenza A, influenza B, human parainfluenza virus 1-4 (HPIV1-4), respiratory syncytial virus (RSV), rubella virus (RV) and Coxsackie virus (CSV), were selected for the development of a multiplex nucleic acid sequence-based amplification (NASBA) assay. Quantifiable measurement utilizing an enzyme-linked oligonucleotide capture (EOC) optical detection method, which was described previously, alleviated the requirement of specialized instrumentation that is commonly used in other molecular techniques. Multiplex NASBA-EOC provided rapid and specific detection of a single virus from a multiplexed group, reducing laboratory testing time and enabling high throughput screening. The uniquely designed primers and probes proved to be highly sensitive and specific, exemplifying the robustness of the multiplex NASBA-EOC technique.
    Journal of virological methods 05/2010; 168(1-2):251-4. · 2.13 Impact Factor
  • Article: [Progress in functional polyphosphate in prokaryotic and eukaryotic living organisms].
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    ABSTRACT: Polyphosphate (poly P) has been widely identified in both inorganic environment and living organisms. Research shows that poly P in bacteria enhances their resistance to severe environment, triggers their protective responses, increases biofilm formation and involves in predation and bacterial virulence. In eukaryotes, poly P has been found to enhance the proliferation of fibroblast and many tumor cell lines, induce the calcification of osteoblast and be involved in calcium ion release. Based on the existing information, we attempt to discuss the possible functions of poly P in the nervous system.
    Sheng li ke xue jin zhan [Progress in physiology] 07/2009; 40(3):197-202.
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    Article: Ischemia activates JNK/c-Jun/AP-1 pathway to up-regulate 14-3-3gamma in astrocyte.
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    ABSTRACT: Ischemia occurs in the brain as the result of stroke and other related injuries and few therapies are effective. If more is understood then potential treatments could be investigated. It was previously reported that 14-3-3gamma could be up-regulated by ischemia in astrocyte to protect cells from ischemia-induced apoptosis. In this study, we attempted to uncover the mechanism responsible for this 14-3-3gamma up-regulation in primary culture of astrocytes under ischemic-like conditions. It was found that in vitro ischemia may activate PI3K/Akt and MAPK signaling pathways. Astrocyte cultures were treated with LY294002 (PI3K inhibitor), U0126 (ERK inhibitor), SB203580 (p38 inhibitor) and SP600125 (JNK inhibitor). Only SP600125 could inhibit the ischemia-induced 14-3-3gamma up-regulation in astrocytes. At the same time, we observed an ischemia-induced nuclear translocation of p-c-Jun, a major downstream component of JNK. Inhibition of AP-1 with curcumin also inhibited 14-3-3gamma up-regulation indicating that ischemia-induced up-regulation of 14-3-3gamma in astrocyte involves activation of the JNK/p-c-Jun/AP-1 pathway.
    Journal of Neurochemistry 05/2009; 109 Suppl 1:182-8. · 4.06 Impact Factor
  • Article: Neutrophils may be a vehicle for viral replication and dissemination in human H5N1 avian influenza.
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    ABSTRACT: The mechanism of systemic spread of H5N1 virus in patients with avian influenza is unknown. Here, H5N1 nucleoprotein and hemagglutinin were identified by immunohistochemistry in the nucleus and cytoplasm of neutrophils in the placental blood of a pregnant woman. Viral RNA was detected in neutrophils by in situ hybridization and enhanced real-time polymerase chain reaction. Therefore, neutrophils may serve as a vehicle for viral replication and transportation in avian influenza.
    Clinical Infectious Diseases 01/2009; 47(12):1575-8. · 9.15 Impact Factor
  • Article: [The impact of antibiotic treatment in patients with influenza-like illness].
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    ABSTRACT: To study the etiology of influenza-like illness (ILI) in Beijing, and to investigate the impact of antibiotic treatment on outcomes. This was a prospective cohort study. Patients with diagnosis of influenza-like illness were prospectively enrolled for study of bacterial and viral pathogens. Demographic characteristics, underlying diseases, respiratory and extrapulmonary symptoms, laboratory tests were also collected for analysis of relationship between drug therapy and outcomes. A total of 476 cases were enrolled between Dec. 2006 and Apr. 2007, of whom 454 cases were used for analysis. Influenza virus was the most common pathogen( n = 197, 43.4%), with other pathogens rarely seen. The mean age of the patients was (33 +/- 13) years, and the ratio of male to female was 1.1:1. Twenty four patients (5.3% ) received influenza vaccine. The rate of antibiotic prescription after onset of illness was 63.4%, but none received antiviral drugs such as Oseltamivir and amantadine. Compared with influenza-negative patients, patients with influenza were older, had more underlying diseases and had greater severity of symptoms such as cough, sore throat, headache and myalgia (but with no statistical differences). The influenza syndrome (T > or = 39 degrees C plus cough, sore throat and headache or myalgia) was more common in the influenza group compared to the influenza-negative patients (P < 0.05). The ratio of antibiotic prescription was 67% in the influenza group, and the total white blood cell and platelet count, percentage of neutrophils were higher in antibiotic treatment patients compared with non-antibiotic treatment patients (P < 0.01). The cost in patients who received antibiotics was twice as much as non-antibiotic treatment patients (P < 0.05), but the defervescence time and respiratory symptom alleviation time did not differ. Cox regression analysis showed that the total white blood count and the differentials (OR value 1.049 and 1.014, respectively), but not antibiotic use were the independent risk factors for longer defervescence time. Influenza virus was the most common pathogen for adult patients with ILI in Beijing city during the winter and the spring seasons. Antibiotic treatment of adult patients with ILI did not improve illness resolution, while the cost was increased significantly.
    Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases 08/2008; 31(7):483-7.
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    Article: Detection of foot-and-mouth disease virus by nucleic acid sequence-based amplification (NASBA).
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    ABSTRACT: A study was conducted to evaluate the performance of a nucleic acid sequence-based amplification (NASBA) assay for the detection of foot-and-mouth disease virus (FMDV). Two detection methods: NASBA-electrochemiluminescence (NASBA-ECL) and a newly developed NASBA-enzyme-linked oligonucleotide capture (NASBA-EOC) were evaluated. The diagnostic sensitivity of these assays was compared with other laboratory-based methods using 200 clinical samples collected from different regions of the world. Assay specificity was also assessed using samples (n=43) of other viruses that cause vesicular disease in livestock and genetic relatives of FMDV. Concordant results were generated for 174/200 (87.0%) of suspect FMD samples between NASBA-ECL and real-time RT-PCR. In comparison with the virus isolation (VI) data, the sensitivity of the NASBA-ECL assay was 92.9%, which was almost identical to that of the real-time RT-PCR (92.4%) for the same set of samples. There was broad agreement between the results of the NASBA-ECL and the simpler NASBA-EOC detection method for 97.1% of samples. In conclusion, this study provides further data to support the use of NASBA as a rapid and sensitive diagnostic method for the detection and surveillance of FMDV.
    Veterinary Microbiology 02/2008; 126(1-3):101-10. · 3.33 Impact Factor
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    Article: Glial cell line-derived neurotrophic factor protects astrocytes from staurosporine- and ischemia- induced apoptosis.
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    ABSTRACT: Glial cell line-derived neurotrophic factor (GDNF) promotes the survival and functions of neurons. It has been shown to be a promising candidate in the treatment of ischemia and other neurodegenerative diseases. We transfected mouse astrocytes in primary cultures with a human GDNF gene and found that their conditioned medium could not only support the growth and survival of cultured dopaminergic neurons but also protect astrocytes from staurosporine- and ischemia-induced apoptosis. This indicated that these transfected astrocytes could release GDNF. A similar protective effect on astrocytes against apoptosis was evident when recombinant human GDNF was used. Moreover, GDNF reduced caspase-3 activity but not that of caspase-1 in cultured astrocytes after ischemia treatment. Thus, GDNF protects astrocytes from apoptosis by inhibiting the activation of caspase-3.
    Journal of Neuroscience Research 12/2007; 85(15):3457-64. · 2.74 Impact Factor
  • Article: H5N1 infection of the respiratory tract and beyond: a molecular pathology study.
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    ABSTRACT: Human infection with avian influenza H5N1 is an emerging infectious disease characterised by respiratory symptoms and a high fatality rate. Previous studies have shown that the human infection with avian influenza H5N1 could also target organs apart from the lungs. We studied post-mortem tissues of two adults (one man and one pregnant woman) infected with H5N1 influenza virus, and a fetus carried by the woman. In-situ hybridisation (with sense and antisense probes to haemagglutinin and nucleoprotein) and immunohistochemistry (with monoclonal antibodies to haemagglutinin and nucleoprotein) were done on selected tissues. Reverse-transcriptase (RT) PCR, real-time RT-PCR, strand-specific RT-PCR, and nucleic acid sequence-based amplification (NASBA) detection assays were also undertaken to detect viral RNA in organ tissue samples. We detected viral genomic sequences and antigens in type II epithelial cells of the lungs, ciliated and non-ciliated epithelial cells of the trachea, T cells of the lymph node, neurons of the brain, and Hofbauer cells and cytotrophoblasts of the placenta. Viral genomic sequences (but no viral antigens) were detected in the intestinal mucosa. In the fetus, we found viral sequences and antigens in the lungs, circulating mononuclear cells, and macrophages of the liver. The presence of viral sequences in the organs and the fetus was also confirmed by RT-PCR, strand-specific RT-PCR, real-time RT-PCR, and NASBA. In addition to the lungs, H5N1 influenza virus infects the trachea and disseminates to other organs including the brain. The virus could also be transmitted from mother to fetus across the placenta.
    The Lancet 10/2007; 370(9593):1137-45. · 38.28 Impact Factor
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    Article: Detection of Newcastle disease virus using nucleic acid sequence-based amplification.
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    ABSTRACT: Newcastle disease (ND) is a contagious and widespread avian disease affecting most species of birds. ND virus (NDV) is the only member of the avian paramyxovirus serotype 1 (APMV1) causing ND outbreak in bird flocks. The technique of nucleic acid sequence-based amplification (NASBA) is a potential method to rapidly and reliably detect NDV isolates. Here, we describe an effective and unprecedented method for detecting NDV strains of all pathotypes. A conserved region of the fusion protein gene was used for designing oligonucleotides specific to all NDV pathotypes. The dynamic range of this NDV NASBA detection method is comparable to virus culture and therefore the NDV NASBA method is a potential alternative for NDV screening and surveillance.
    Biologicals 04/2007; 35(1):13-8. · 1.70 Impact Factor
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    Article: The novel neurotrophin-regulated neuronal development-associated protein, NDAP, mediates apoptosis.
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    ABSTRACT: We identified a novel gene and named it, "neuronal development-associated protein (NDAP)". We detected NDAP mRNA presence in most tissues including the brain where it was present in the area from the external granular layer to the multiform layer in the cerebral cortex, and in CA1, CA2, CA3 and the dentate gyrus in the hippocampus. Its expression increased transiently in primary cultures of 2-4 day neurons and 1-2 week astrocytes and was significantly reduced in older cultures. Treatment by the neurotrophin, NT-3, significantly attenuated the decline of NDAP in neurons from days 2 to 10, whereas growth factors such as GDNF and insulin, and high potassium levels did not. To elucidate the effects of neurotrophins, we treated day 5 neurons with NT-3, BDNF or NGF for 48 h. NT-3 and BDNF both inhibited downregulation of NDAP mRNA levels but NGF slightly enhanced the already present downregulation; this effect of NGF was significant when examined in day 3 neurons. To investigate the potential function of NDAP, we over-expressed an NDAP-EGFP fusion protein in 4-week-old astrocytes. The newly expressed NDAP gradually aggregated into membrane-bound structures and eventually led to cell death through apoptosis by 24 h. Significant levels of cell death were also observed in NDAP-EGFP transfected HEK293 cells. Thus maintenance of high NDAP levels may cause apoptosis. The different regulations of NDAP expression by neurotrophins indicate that the expression of NDAP might be a checkpoint for apoptosis during neuronal development.
    FEBS Letters 04/2006; 580(7):1723-8. · 3.54 Impact Factor
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    Article: Identification of a mouse synaptic glycoprotein gene in cultured neurons.
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    ABSTRACT: Neuronal differentiation and aging are known to involve many genes, which may also be differentially expressed during these developmental processes. From primary cultured cerebral cortical neurons, we have previously identified various differentially expressed gene transcripts from cultured cortical neurons using the technique of arbitrarily primed PCR (RAP-PCR). Among these transcripts, clone 0-2 was found to have high homology to rat and human synaptic glycoprotein. By in silico analysis using an EST database and the FACTURA software, the full-length sequence of 0-2 was assembled and the clone was named as mouse synaptic glycoprotein homolog 2 (mSC2). DNA sequencing revealed transcript size of mSC2 being smaller than the human and rat homologs. RT-PCR indicated that mSC2 was expressed differentially at various culture days. The mSC2 gene was located in various tissues with higher expression in brain, lung, and liver. Functions of mSC2 in neurons and other tissues remain elusive and will require more investigation.
    Neurochemical Research 11/2005; 30(10):1289-94. · 2.24 Impact Factor
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    Article: Minocycline inhibits LPS-induced retinal microglia activation.
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    ABSTRACT: Retinal neurodegenerative disease involves an inflammatory response in the retina characterized by an increase in inflammatory cytokines and activation of microglia. The degree of microglia activation may influence the extent of retinal injury following an inflammatory stimulus. Cytokines released by activated microglia regulate the influx of inflammatory cells to the damaged area. Thus, a therapeutic strategy to reduce cytokine expression in microglia would be neuroprotective. Minocycline, a semisynthetic tetracycline derivative, is known to protect rodent brain from ischemia and to inhibit microglial activation. In this study, we activated retinal microglia in culture with lipopolysaccharide (LPS) and attempted to determine whether minocycline could reduce the production of cytokines from activated microglia at both gene and protein levels. Changes in inflammatory cytokines, TNF-alpha and IL-1beta, were measured by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) in the presence or absence of LPS. We also measured the levels of nitric oxide (NO) by the nitrate reductase method under similar conditions. LPS treatment induced a significant upregulation of the mRNA and release of TNF-alpha, IL-1beta, and NO from retinal microglia. Minocycline inhibited these releases. Thus, minocycline might exert its antiinflammatory effect on microglia by inhibiting the expression and release of TNF-alpha, IL-1beta, and NO.
    Neurochemistry International 08/2005; 47(1-2):152-8. · 2.86 Impact Factor
  • Article: Presence of neuroglobin in cultured astrocytes.
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    ABSTRACT: Neuroglobin (Ngb), a recently discovered intracellular respiratory globin in neurons, may play a crucial role in oxygen homeostasis in the brain. We report preliminary findings indicating the presence of functional neuroglobin in primary cultures of cerebral cortical astrocytes. Reverse transcription real-time polymerase chain reaction (RRT-PCR) and immunostaining confirmed such presence in cultured astrocytes isolated from newborn mouse brain. Ngb antisense treatment increased apoptosis in ischemic astrocytes. The discovery of Ngb in astrocytes may provide some insight into how oxygen homeostasis is regulated in the brain.
    Glia 05/2005; 50(2):182-6. · 4.82 Impact Factor
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    Article: Inactivation of bad by site-specific phosphorylation: the checkpoint for ischemic astrocytes to initiate or resist apoptosis.
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    ABSTRACT: Bcl-2-associated death protein (Bad), a member of the Bcl family, directs astrocytes in primary cultures to enter or resist apoptosis during ischemia in vitro. Under ischemia, Bad was the only Bcl family member whose expression was upregulated significantly during the early stages of an ischemic insult. Increased endogenous Bad was translocated from the cytoplasm to mitochondria to induce apoptosis in astrocytes. Concurrently, ischemia also induced Bad phosphorylation specifically on Ser112 to promote survival. This site-specific phosphorylation of Bad was mediated by an early activation of the mitogen-activated protein kinase/extracellular signal-regulated protein kinase (MAPK/ERK) intracellular signaling pathway. This study demonstrates that ischemia-induced Bad plays a dual role in determining whether astrocytes enter or resist apoptosis after an ischemic insult.
    Journal of Neuroscience Research 04/2005; 79(6):798-808. · 2.74 Impact Factor
  • Article: A model to induce low temperature trauma for in vitro astrogliosis study.
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    ABSTRACT: Astrogliosis is an inevitable and rapid response of astrocytes to physical, chemical and pathological injuries. To study astrogliosis, we developed a reproducible in vitro model in which low temperature injury to cultured astrocytes could be induced by placing the culture dish onto a copper pipe pre-cooled by liquid nitrogen. Using this model, the relationship between the temperature decline and the severity of cellular damage was analyzed. An increase in the expression of some known injury-related proteins, such as glial fibrillary acidic protein (GFAP), immediate early response genes (IEGs), and heat shock proteins 70 (HSP70), was demonstrated in astrocytes after low temperature trauma. With the use of this low temperature trauma model, the flexibility in the temperature control and injury area may allow researchers to evaluate cryotherapy and cryosurgery, which could be applicable to future development of quality health care.
    Neurochemical Research 12/2004; 29(11):2171-6. · 2.24 Impact Factor
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    Article: Genome comparison of a novel foot-and-mouth disease virus with other FMDV strains.
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    ABSTRACT: The genome of a novel foot-and-mouth disease virus, HKN/2002, was 8104 nucleotides (nt) in length (excluding the poly(C) tract and poly(A) tail) and was composed of a 1042-nt 5'-untranslated region (UTR), a 6966-nt open reading frame, and a 93-nt 3'-UTR. Genome sequences of HKN/2002 and other known FMDV strains were compared. The VP1, VP2, and VP3-based neighbor-joining (NJ) trees were divided into distinct clusters according to different serotypes, while other region-based NJ trees exhibited some degree of intercross among serotypes. Mutations in HKN/2002 were revealed, including frequent deletions and insertions in the G-H loop of VP1, and deletion involving 10 amino acid residues in the 3A protein. An evolutionary relationship of HKN/2002 with an Asian FMDV lineage isolated from a Hong Kong swine host in 1970 was postulated. A 43-nt deletion identified in the 5'-UTR of HKN/2002 possibly contributed to the loss of one pseudo-knot domain.
    Biochemical and Biophysical Research Communications 11/2004; 323(1):254-63. · 2.48 Impact Factor
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    Article: Use of clinical criteria and molecular diagnosis to more effectively monitor patients recovering after severe acute respiratory syndrome coronavirus infection.
    Clinical Infectious Diseases 09/2004; 39(4):604-6. · 9.15 Impact Factor
  • Article: Boosting the sensitivity of real-time polymerase-chain-reaction testing for SARS.
    New England Journal of Medicine 05/2004; 350(15):1577-9. · 53.30 Impact Factor

Institutions

  • 2004–2011
    • Peking University
      • Neuroscience Research Institute
      Beijing, Beijing Shi, China
  • 2007
    • Harbin Veterinary Research Institute
      Harbin, Heilongjiang Sheng, China
  • 2003
    • Wenzhou Entry-Exit Inspection and Quarantine Bureau of P.R.C
      Wenzhou, Zhejiang Sheng, China