Biomedical subjects
Publications and source records attributed to J Lu.
We report a high-efficiency diode-end-pumped polycrystalline Yb:Y2O3 ceramic laser. Pumped by a 976 nm laser diode bar and with an absorbed pump power of 2.8 W, cw output power of 1.74 W at 1078 nm, and 0.73 W at 1040 nm were obtained. The slope efficiency was measured to be 82.4% for the 1078 nm laser emission and 57.1% for the 1040 nm laser emission.
This study investigated whether each part of the heart is evenly innervated by the left or right vagus and observed the mechanism of compensatory recovery after unilateral cervical vagotomy. HR, BP, LVSP and +/-dp/dt max all decreased one week after left vagotomy, whereas only BP and -dp/dt max decreased one week after right vagotomy. Western blot analyses revealed that the expression of M(2) receptors in the left atrium and left ventricle was upregulated after subacute (1 week) left/right vagotomy. However, significantly more cholinesterase-positive nerves in LV and RV were seen one week after unilateral vagotomy compared to the sham-operated group. In addition, baroreflex sensitivity was increased after subacute right vagotomy. The decreasing effects of ACh (0.5 microg/kg) on LVSP and +/-dp/dt max (but not on HR and BP) were facilitated by subacute unilateral vagotomy. Our present experiments indicate that 1) the working myocardium is innervated bilaterally by the vagus, 2) ventricular contractility is influenced more by denervation of the left than the right vagus and 3) up-regulation of M(2) muscarinic receptors in the left heart, increase of cholinergic nerves, and high baroreflex sensitivity could be involved in the mechanism of compensatory hemodynamic recovery via contralateral vagus overactivity, thereby amplifying contralateral vagal activity and decreasing cardiac contractility.
The PathoSystems Resource Integration Center (PATRIC) is one of eight Bioinformatics Resource Centers (BRCs) funded by the National Institute of Allergy and Infection Diseases (NIAID) to create a data and analysis resource for selected NIAID priority pathogens, specifically proteobacteria of the genera Brucella, Rickettsia and Coxiella, and corona-, calici- and lyssaviruses and viruses associated with hepatitis A and E. The goal of the project is to provide a comprehensive bioinformatics resource for these pathogens, including consistently annotated genome, proteome and metabolic pathway data to facilitate research into counter-measures, including drugs, vaccines and diagnostics. The project's curation strategy has three prongs: 'breadth first' beginning with whole-genome and proteome curation using standardized protocols, a 'targeted' approach addressing the specific needs of researchers and an integrative strategy to leverage high-throughput experimental data (e.g. microarrays, proteomics) and literature. The PATRIC infrastructure consists of a relational database, analytical pipelines and a website which supports browsing, querying, data visualization and the ability to download raw and curated data in standard formats. At present, the site warehouses complete sequences for 17 bacterial and 332 viral genomes. The PATRIC website (https://patric.vbi.vt.edu) will continually grow with the addition of data, analysis and functionality over the course of the project.
The aim of this study was to investigate the immunomodulatory effects and mechanism of action of alpha-melanocyte-stimulating hormone (alpha-MSH) gene modified proteolipid protein (PLP) 139-151-specific T cells (T(PLP-alpha-MSH)) in the SJL mouse model of experimental autoimmune encephalomyelitis (EAE). PLP139-151-specific T cells (T(PLP) cells) were transduced with a recombinant adeno-associated virus 2 (rAAV2) encoding alpha-MSH. After activation with PLP139-151 in vitro, T(PLP-alpha-MSH) cells secreted high levels of alpha-MSH and also demonstrated an altered Th1-like cytokine pattern as well as a high frequency of CD4(+)CD25(+)Treg cells. Transfer studies showed that T(PLP-alpha-MSH) cells could suppress the induction of adoptive transfer EAE. More importantly, our studies demonstrated that T(PLP-alpha-MSH) cells had preventive and therapeutic effect on active relapse-remitting EAE (REAE) in an antigen-inducible manner. Suppression of REAE by T(PLP-alpha-MSH) cells was associated with a general reduction of inflammatory central nervous system (CNS) infiltrates, a pronounced decrease in Th1 cytokines and chemokines expression and an increase in Th2 cytokines. These data strongly suggested that local delivery of alpha-MSH by rAAV2-mediated alpha-MSH-transduced PLP139-151-specific T cells (T(PLP-alpha-MSH)) would be a desirable new approach to the treatment of autoimmune disease in the CNS.
The smoky-brown cockroach (Periplaneta fuliginosa) densovirus (PfDNV) has previously shown potential in urban pest control. To improve its efficacy as a biopesticide, the genome of PfDNV was engineered by inserting the insect-specific toxin gene BmKIT1 in the open reading frame encoding the major structural proteins. A green fluorescent protein (GFP) marker was tagged to the BmKIT1 at its C-terminus for in vivo imaging using Confocal laser scanning microscopy (CFSM). Using a virion rescue strategy, the genomes of recombinant and wild-type (wt) PfDNV were then cotransfected in P. fuliginosa nymphs. Reverse transcription PCR (RT-PCR) showed that the inserted BmkIT1 genes were expressed in the P. fuliginosa nymphs 48 h after cotransfection. CFSM and transmission electron microscopy also confirmed the generation of virus particles and expression of BmKIT1-GFP fusion protein in the cotransfected nymphs. The recombinant viruses remained infective to P. fuliginosa nymphs in feeding tests. Using the LT(50) bioassay method, the coninfection of the recombinant and wt PfDNV killed the P. fuliginosa nymphs approximate 32% faster than wt PfDNV only. This is the first report showing the improvement of engineered densovirus for the potential application of biopesticide.
Pentobarbital microinjected into a restricted locus in the upper brainstem induces a general anesthesia-like state characterized by atonia, loss of consciousness, and pain suppression as assessed by loss of nocifensive response to noxious stimuli. This locus is the mesopontine tegmental anesthesia area (MPTA). Although anesthetic agents directly influence spinal cord nociceptive processing, antinociception during intracerebral microinjection indicates that they can also act supraspinally. Using neuroanatomical tracing methods we show that the MPTA has multiple descending projections to brainstem and spinal areas associated with pain modulation. Most prominent is a massive projection to the rostromedial medulla, a nodal region for descending pain modulation. Together with the periaqueductal gray (PAG), the MPTA is the major mesopontine input to this region. Less dense projections target the PAG, the locus coeruleus and pericoerulear areas, and dorsal and ventral reticular nuclei of the caudal medulla. The MPTA also has modest direct projections to the trigeminal nuclear complex and to superficial layers of the dorsal horn. Double anterograde and retrograde labeling at the light and electron microscopic levels shows that MPTA neurons with descending projections synapse directly on spinally projecting cells of rostromedial medulla. The prominence of the MPTA's projection to the rostromedial medulla suggests that, like the PAG, it may exert antinociceptive actions via this bulbospinal relay.
This study examined the nestin immunoexpression and its specific cellular localization in the developing retina of rats and investigated its putative changes in an altered environment. At postnatal day 0, nestin immunoexpression was detected in radially oriented cells considered to be neural progenitors that were glutamine synthetase (GS) negative. With age, it was localized in differentiating and differentiated GS positive Müller glial cells. Nestin expression was down-regulated as maturation proceeded, so that by 12 weeks, it was almost completely diminished as confirmed also by real time-polymerase chain reaction analysis. Nestin expression along with that of glial fibrillary acidic protein (GFAP) was induced and upregulated in mature Müller glial cells following optic nerve transection. It is suggested that both nestin and GFAP may be useful biomarkers in retinal injuries. In view of their cytoskeletal nature, the marked expression of nestin and GFAP may provide a structural support for the framework of retina which would be disrupted as a result of loss of neurons in optic nerve lesion. It may also be neuronal protective taking into consideration the close spatial and functional links between Müller glial cells and the axotomized ganglion cells.
Expression of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) in amoeboid microglial cells (AMC) in developing rat brain from prenatal day 18 (E18) to postnatal day 10 (P10) was demonstrated by immunohistochemistry/immunofluorescence and immunoelectron microscopy both in vivo and in vitro, respectively. Furthermore, real time-polymerase chain reaction (PCR) was performed to determine the expression of CNPase at mRNA level in cultured microglial cells in control conditions and following lipopolysaccharide stimulation. CNPase immunoreactive amoeboid microglia occurred in large numbers in the corpus callosum, subventricular zone and cavum septum pellucidum at P0 but were progressively reduced with age and were undetectable at P14. By immunoelectron microscopy, immunoreaction product was associated primarily with the plasma membrane, filopodial projections and mitochondria in AMC. Real time-PCR analysis revealed that CNPase mRNA was expressed by cultured amoeboid microglia and was significantly up-regulated in microglial activation induced in vitro by lipopolysaccharide. The functional role of CNPase in AMC remains speculative. Given its expression in AMC transiently occurring in the perinatal brain and that it is markedly elevated in activated microglia, it is suggested that the enzyme may be linked to the major functions of the cell type such as release of chemokines and cytokines. In relation to this, CNPase may play a key role associated with transportation of cytoplasmic materials.
In mammals and Drosophila, apoptotic caspases are under positive control of the CED-4-like proteins Apaf-1 and ARK, respectively. In an EMS-mutagenesis screen, we isolated 33 ark mutants as recessive suppressors of hid-induced apoptosis. The ark mutants are loss-of-function alleles characterized by reduced developmental apoptosis. Using the phenotypic series of these alleles, we identified helical domain I in the nucleotide oligomerization domain as critical for ARK's apoptotic activity. Interestingly, the WD40 region may also have an unanticipated positive requirement for the apoptotic activity of ARK. Considering structural information, we discuss the roles of these domains for assembly and activity of the ARK apoptosome, and propose that the WD40 region is anti-apoptotic in the absence of apoptotic signals, and pro-apoptotic in the presence of such signals. Furthermore, a defined null allele reveals that ark is required for most, but not all apoptosis suggesting the existence of an ARK-independent apoptotic pathway.
The first measurements of double-hadron production in deep-inelastic scattering within the nuclear medium were made with the HERMES spectrometer at DESY HERA using a 27.6 GeV positron beam. By comparing data for deuterium, nitrogen, krypton, and xenon nuclei, the influence of the nuclear medium on the ratio of double-hadron to single-hadron yields was investigated. Nuclear effects on the additional hadron are clearly observed, but with little or no difference among nitrogen, krypton, or xenon, and with smaller magnitude than effects seen on previously measured single-hadron multiplicities. The data are compared with models based on partonic energy loss or prehadronic scattering and with a model based on a purely absorptive treatment of the final-state interactions. Thus, the double-hadron ratio provides an additional tool for studying modifications of hadronization in nuclear matter.
OBJECTIVE: To investigate the impact of lipoprotein lipase (LPL) gene S447X polymorphism on the relation between central obesity and lipid levels. DESIGN: A total of 961 adult twin pairs were included from the program of Chinese Twin Registry, between 2001 and 2002. Central obesity was defined as waist circumference > or =90 cm for male and > or =80 cm for female. Two statistical methods were performed to test the modification effect of S447X polymorphism of LPL gene on the relation between central obesity and lipid levels: one was Generalized Estimating Equation (GEE) models for all twin pairs and the other was co-twin matched case-control analysis in 82 central obesity discordant monozygotic twin pairs. RESULTS: In GEE models for all twins, central obesity was significantly associated with serum lipids except for high-density lipoprotein (HDL), while X447 allele had favorable effects on the levels of triglyceride (TG), HDL and TG to HDL ratio (TG/HDL). The interactions of S447X polymorphism and central obesity were statistically significant for TG/HDL and HDL. In central obesity discordant monozygotic twin pairs, central obesity was significantly related with 26.2% increase of TG and 27.2% increase of TG/HDL in S/S447 genotype, while in 447X allele carrier, central obesity was significantly related with 13.7% increase of HDL. CONCLUSION: These results suggest that LPL gene S447X polymorphism modifies the relation between central obesity and serum lipids, which also stresses the importance of reducing waist circumference to improve serum lipids for people with central obesity, especially those with S/S447 genotype.
This study was aimed to investigate reactive changes of Müller glial cells in rats subjected to experimentally induced glaucoma. In the latter, it is well documented that elevated intraocular pressure leads to the loss of ganglion cells as confirmed in this study. The present results have shown that Müller glial cells as well as astrocytes closely associated with the ganglion cells reacted vigorously to increased intraocular pressure as manifested by the induced and upregulated expression of nestin and glial fibrillar acidic protein. A major finding in glaucomatous rats was the induced expression of nestin together with glial fibrillar acidic protein with the rise of the intraocular pressure beginning at 2 h. The marked nestin expression appeared to be most intense at 1 week after operation and was sustained at 3 weeks. Induced nestin expression in Müller glial cells was demonstrated unequivocally in whole-mount preparation of the retina. In the same tissue preparation, nestin expression was also detected in some astrocytes. Western blotting analysis confirmed a marked increase in expression of nestin and glial fibrillar acidic protein. Present results suggest that nestin as well as glial fibrillar acidic protein is a useful biomarker for retina injury. The induced expression of these intermediate filament proteins in Müller glial cells especially at their end-feet and also in some astrocytes adjoining the neuronal injury suggests a potential neuroprotective mechanism in response to acute rise in intraocular pressure resulting in neuronal degeneration.
The dried ripe fruit of Vitex agnus-castus L. (VAC) is widely used for the treatment of premenstrual syndrome (PMS). A previous study reported that extracts of VAC showed affinity to opiate receptors; however, functional activity was not determined. We tested two different VAC extracts in receptor binding and functional assays. Our objectives were: (1) to confirm the opiate affinity; (2) to rule out interference by free fatty acids (FFA); (3) to determine the mode of action of VAC at the mu-opiate receptor. Methanol extracts of VAC were prepared either before (VAC-M1) or after (VAC-M2) extraction with petroleum ether to remove fatty acids. Both extracts showed significant affinities to the mu-opiate receptor, as indicated by the concentration-dependent displacement of [3H]DAMGO binding in Chinese hamster ovary (CHO)-human mu-opiate receptor (hMOR) cells. The IC50 values were estimated to be 159.8 microg/ml (VAC-M1) and 69.5 microg/ml (VAC-M2). Since the defatted extract not only retained, but exhibited a higher affinity (p<0.001), it argued against significant interference by fatty acids. In an assay to determine receptor activation, VAC-M1 and VAC-M2 stimulated [35S]GTPgammaS binding by 41 and 61% (p<0.001), respectively. These results suggested for the first time that VAC acted as an agonist at the mu-opiate receptor, supporting its beneficial action in PMS.
Haemophilia A treatment is an attractive candidate for gene therapy. The aim of haemophilia gene therapy is to obtain long-term therapeutic level of factor VIII (FVIII). We investigated Epstein-Barr virus (EBV)-based episomal vector combined with in vivo electroporation of naked DNA as a safe, efficient and simple method for correcting FVIII deficiency. A combinant FVIII expression EBV-based episomal vector pcDNA3-FVIII-EBVR was constructed and expressed in COS-7 cells. Then the naked plasmid DNA was injected into the quadriceps of mice following the electric pulse stimulation. Our data showed that pcDNA3-FVIII-EBVR expression in transfected COS-7 can maintain stably for at least 60 days and the hFVIII:Ag in plasma in two pcDNA3-FVIII-EBVR groups mice was higher than that in pcDNA-FVIII groups no matter with or without electric pulse stimulation. With the stimulating of electric pulse, the FVIII expression in plasma of recipient mice was increased two- to fourfolds and can be lasted for at least 90 days. No severe muscle damage was detected. So this novel strategy that FVIII expression mediated by EBV episomal vector following muscle electroporation is efficient, safe, simple and economic and may be applicable to clinical usage.
Synthetic oligodeoxynucleotides (ODN) containing unmethylated cytosine guanine (CpG) dinucleotides motifs act as immune adjuvant and provide means of modulation to immune responses when co-delivered with antigens. They stimulate both innate and adaptive immune responses and induce T helper 1 (Th1) immune responses. We investigated the immunomodulation of Japanese encephalitis (JE) vaccine using CpG ODN as an adjuvant. Mice were immunized with one dose of JE vaccine 0.1 ml with different concentrations (10, 25 and 100 microg) of CpG ODN. The serum antibody level and cytokines were evaluated and compared with mice immunized with two doses of JE vaccine alone. Our studies revealed that anti-JE antibody level in mice immunized with single dose of 0.1 ml JE vaccine and 100 microg CpG ODN were almost equal to mice immunized with two doses of JE vaccine alone. Furthermore, CpG ODN enhanced the production of TNF-alpha and Th1-mediated cytokines, including IFN-gamma and IL-2 compared with JE vaccine alone. In addition, absence of any significant changes in biochemical, haematological and histological studies suggest that CpG ODN are safe adjuvants for JE vaccine. Therefore, it is inferred that CpG ODN are effective and improve the efficacy of JE vaccine.
AIMS: Previous studies have shown that the peroxisome proliferator-activated receptor delta (PPARD) genetic polymorphism affects cholesterol metabolism in Whites. This association was not observed in a Korean population in a separate study, but this study showed a link between the PPARD polymorphism and body weight and fasting plasma glucose. The purpose of this study was to determine whether polymorphisms of PPARD influence glucose and cholesterol metabolism in Chinese subjects. We investigated the association between the polymorphism (-87T/C) of the human PPARD gene and phenotypes related to body weight, insulin sensitivity, glucose and lipid metabolism in Chinese subjects. METHODS: Unrelated Chinese subjects (n = 663) in Shanghai were studied; 287 had newly diagnosed Type 2 diabetes mellitus and 376 were non-diabetic control subjects over 40 years old. Clinical parameters were collected and genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: In normal glucose tolerant (NGT) subjects, the C allele carriers had higher fasting plasma glucose concentrations (P = 0.0078) and a lower insulin sensitivity index (ISI) (P = 0.0365). The C allele carriers also showed higher concentrations of low-density lipoprotein cholesterol (P = 0.0261) and percentage of body fat (P = 0.0357). There was a trend towards higher visceral adiposity in C allele carriers, but the difference was not significant (P = 0.0830). In diabetes patients, similar results were detected for plasma glucose concentrations (fasting plasma glucose P < 0.0001, 2-h plasma glucose P = 0.0052) and insulin sensitivity (homeostasis model assessment of insulin resistance P = 0.0094; ISI P = 0.0058). CONCLUSION: The PPARD-87T/C polymorphism is associated with higher fasting plasma glucose concentrations in both NGT and diabetic subjects, largely due to impaired insulin sensitivity.
In the present study, DNA typing for HLA-DPB1 was performed using polymerase chain reaction-sequencing-based typing method in 72 randomly selected Nu ethnic individuals inhabiting the Yunnan province of south-west China. Among the 12 detected DPB1 alleles, the most frequent was DPB1*1301, with the percentage of 20.83%, followed by DPB1*0501 (19.44%), DPB1*040101 (16.67%) and DPB1*2801 (9.72%). The allele DPB1*1501 was found for the first time in the Chinese population. Neighbour-joining showed that the Nu ethnic minority belonged to East Asian cluster and was most closely related to Lisu, being consistent with the historical records. In addition, the results obtained in this study will also provide useful information on organ transplantation, forensic investigations and disease association studies.
BACKGROUND: Recruitment and retention of dentists in the public sector and rural areas in Victoria has become increasingly difficult in recent years. There are little available data on the factors that influence the sector and location of practice of new dental graduates. The objective of this study was to investigate the factors considered by new graduates in determining the location and sector of employment after graduation, and influencing any early changes in career path. METHODS: Questionnaires were sent to dentists who Mgraduated from The Univrersity of Melbourne from graduated from The University of Melbourne from 2000-2003 who were currently practising in Victoria. There were 154 subjects to whom questionnaires were sent and 109 useable questionnaires were returned, a response rate of 74 per cent. RESULTS: Upon graduation, 53 per cent of the new graduates chose to work in the private sector only, compared to 15 per cent in public sector only and 33 per cent in both. At present, 71 per cent work in the private sector only, 17 per cent in the public sector only and 12 per cent in both. The most important factors for choosing to work in the private sector were receiving broad range of clinical experience, opportunities to familiarize with practice management and providing a continuity of care. The principal factors for practising in the public sector were clinical mentoring and advice, consolidating clinical skills and work environment. Initially, 48 per cent of the sample chose to work in metropolitan areas only, 39 per cent in rural areas only and 13 per cent in both. Factors that influenced the decision to work in rural areas were the broad range of clinical experience and remuneration, while the main factors for choosing to work in metropolitan areas were lifestyle and proximity to family and friends. CONCLUSIONS: This study found that a large proportion of new dental graduates initially chose to work in the public sector and rural areas on graduation primarily as a means of consolidating their clinical skills. However, retention of dentists in both these areas appears to be a problem, with less than 10 per cent of 2000-2001 graduates still than 10 per cent of 2000-2001 graduates still working in the public sector and only 20 per cent of 2000-2001 graduates still working in rural areas.