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Biomedical subjects

N Lu

Publications and source records attributed to N Lu.

At least 19 recordsLinked to original sources
PubMed2006

P13 of Leucania separata multiple nuclear polyhedrosis virus affected the polyhedra and budded virions yields of AcMNPV.

p13 gene was first described by our laboratory in Leucania separata multiple nuclear polyhedrovirus (Ls-p13, ORF114) back to 1995. However, the functions of Ls-P13 and its reported homologues remained unknown. In order to probe the function of Ls-P13, recombinant Autographa californica nucleopolyhedroviruses (rAcMNPVs) were constructed to express Ls-P13 in the Sf9 cells at early, late or early/late phase. Observations of microscope showed that the expression of Ls-P13 could decrease the yield of AcMNPV polyhedra in Sf9 cells, and early expressed Ls-P13 had stronger inhibition efficiency than that of the late expressed. Results of flow cytometry also indicated that Ls-P13 decreased the yield of AcMNPV polyhedra while increased those of budded virions (BVs) in Sf9 cells, but the efficacy was lost when its leucine zipper-like domain was mutated. Ls-P13 is a transmembrane protein, which was early located in the nucleus and late mainly in the cytoplasm membrane at 48 h. When its transmembrane domains were deleted, Ls-P13 distribution was dramatically diverted from cytoplasm membrane to nucleus, its corresponding efficacy on polyhedra yield was further increased while that on BVs was slightly weakened. Bioassay results indicated that Ls-P13 accelerated the larvae-killing rate. The mechanism might be that Ls-P13 increased BV yield.

Animals↗
PubMed2006

Laser-induced chorioretinal venous anastomosis using combined lasers with different wavelengths.

AIM: To evaluate the effectiveness of combined lasers with different wavelengths in creating chorioretinal venous anastomosis (CRVA) in nonischaemic central retinal vein occlusion (CRVO). METHODS: In this retrospective, noncomparative, consecutive case series, records of all patients with a diagnosis of nonischaemic CRVO who underwent combined laser treatment to induce CRVA and who were followed-up for 6 months or longer were reviewed. RESULTS: Records of 85 patients (85 eyes) were analysed. These patients were divided into two groups. In group 1 (24 cases, 24 eyes), combined lasers with two different wavelengths (argon blue-green laser combined with Nd-YAG laser were used. In group 2 (61 cases, 61 eyes), combined lasers with three different wavelengths (argon blue-green laser combined with krypton red laser and Nd-YAG laser) were used. Functional anastomosis formed in 13 out of 24 eyes (54%) in group 1 and 47 out of 61 eyes (77%) in group 2. In patients with successful anastomosis, visual acuity improved for two or more lines in 49 out of 60 eyes (82%), with the remaining eyes undergoing no change. There were no serious complications. CONCLUSION: The use of three laser wavelengths results in the creation of laser anastomosis and the success rate may be higher than when using two wavelengths alone.

Adolescent↗
PubMed2006

The study of peripheral blood mononuclear cell MHC I and MHC II gene mRNA expression in acute graft rejection.

BACKGROUND: Early diagnosis of acute graft rejection is important in the clinic. To explore a reliable diagnostic marker, we selected skin-grafted rabbits as an animal model to study peripheral blood mononuclear cell (PBMC) major histocompatibility complex 1 (MHC I) and MHC II gene mRNA in acute graft rejection (AGR). METHODS: Fifteen New Zealand white rabbits were randomly divided into three groups to observe skin graft rejection: three rabbits were in the autograft control group; six rabbits in a cyclosporine (CsA) treated allografted group; and the other six rabbits in untreated allografted group. The CsA-treated allografted group was given CsA (5 mg/kg) daily intramuscularly. PBMC samples were obtained every 2 days to detect by real-time polymerase chain reaction, PBMC MHC I and MHC II gene mRNA. RESULTS: MHC I and MHC II gene mRNA levels did not show any obvious change in the autografted controls. MHC I gene mRNA levels showed a slow increase in the CsA-treated allografted group, but no obvious change in the untreated allografted group. MHC II gene mRNA reached the highest level at 2 to 3 days before graft rejection appeared macroscopically in the CsA-treated allografted group and untreated allografted group, then decreasing to a low level. CONCLUSION: Compared with MHC I gene mRNA expression, PBMC MHC II gene mRNA expression may be considered to be an earlier marker for AGR.

Acute Disease↗
PubMed2005

Risk factors for oesophageal squamous dysplasia in adult inhabitants of a high risk region of China.

BACKGROUND: Oesophageal squamous cell carcinoma (OSCC) is a common cancer worldwide and has a very high mortality rate. Squamous dysplasia is the precursor lesion for OSCC and it can be seen during routine endoscopy with Lugol's iodine staining. We aimed to examine the risk factors for squamous dysplasia and determine if a risk model could be constructed which would be useful in selecting apparently healthy subjects for endoscopic screening in a high risk population in Linzhou, People's Republic of China. SUBJECTS AND METHODS: In this cross sectional study, 724 adult volunteers aged 40-65 years were enrolled. All subjects completed a questionnaire regarding potential environmental exposures, received physical and dental examinations, and underwent upper endoscopy with Lugol's iodine staining and biopsy. Subjects were categorised as having or not having histologically proven squamous dysplasia/early cancer. Risk factors for dysplasia were examined using univariate and multivariate logistic regression. The utility of the final multivariate model as a screening tool was assessed using a receiver operating characteristics curve. RESULTS: We found that 230 of 720 subjects (32%) with complete data had prevalent squamous dysplasia. In the final multivariate model, more household members (odds ratio (OR) 1.12/member (95% confidence interval (CI) 0.99, 1.25)), a family history of cancer (OR 1.57 (95% CI 1.13-2.18)), higher systolic blood pressure OR 1.11/10 mm Hg (95% CI 1.03-1.19)), heating the home without a chimney (OR 2.22 (95% CI 1.27-3.86)), and having lost more but not all of your teeth (OR 1.91 for 12-31 teeth lost (95% CI 1.17-3.15)) were associated with higher odds of having dysplasia. Higher household income (OR 0.96/100 RMB (95% CI 0.91-1.00)) was associated with a lower odds of having dysplasia. Although we found several statistically significant associations, the final model had little ability to accurately predict dysplasia status, with maximum simultaneous sensitivity and specificity values of 57% and 54%, respectively. CONCLUSIONS: We found that risk factors for dysplasia were similar to those previously identified as risk factors for OSCC in this population. The final model did a poor job of identifying subjects who had squamous dysplasia. Other methods will need to be developed to triage individuals to endoscopy in this high risk population.

Adult↗
PubMed2004

An efficient algorithm for optimizing whole genome alignment with noise.

MOTIVATION: This paper is concerned with algorithms for aligning two whole genomes so as to identify regions that possibly contain conserved genes. Motivated by existing heuristic-based software tools, we initiate the study of an optimization problem that attempts to uncover conserved genes with a global concern. Another interesting feature in our formulation is the tolerance of noise, which also complicates the optimization problem. A brute-force approach takes time exponential in the noise level. RESULTS: We show how an insight into the optimization structure can lead to a drastic improvement in the time and space requirement [precisely, to O(k2n2) and O(k2n), respectively, where n is the size of the input and k is the noise level]. The reduced space requirement allows us to implement the new algorithm, called MaxMinCluster, on a PC. It is exciting to see that when tested with different real data sets, MaxMinCluster consistently uncovers a high percentage of conserved genes that have been published by GenBank. Its performance is indeed favorably compared to MUMmer (perhaps the most popular software tool for uncovering conserved genes in a whole-genome scale). AVAILABILITY: The source code is available from the website http://www.csis.hku.hk/~colly/maxmincluster/ detailed proof of the propositions can also be found there.

Algorithms↗
PubMed2004

Child day care risks of common infectious diseases revisited.

BACKGROUND: The increased risk of common infectious diseases associated with child day care attendance may vary by age, health plan and parent educational level. This study determined quantitatively the risk of diarrhoeal illness and upper respiratory infection (URI) among day-care children in comparison with home-care children. It examined the extent of risks in day-care children under different conditions of three age groups, enrolled in two health plans, and from families of two levels of education. METHODS: The study subjects were recruited through two health plans: a Health Maintenance Organization (HMO) and the Medicaid program in Columbia, South Carolina of the USA. The sample was collected using a household survey of children, aged 5 years or younger. The participants were contacted bimonthly for 18 months with 435 attending out-of-home day care facilities and 753 being cared for at home. The potential confounding factors of family characteristics were controlled in examining the odds ratios for day care effect on common infections in children under different conditions. RESULTS: In general, risks of diarrhoeal illness and URI in day-care children are greater than in home-care children. Children younger than 1.5 years of age attending day care and covered by the Medicaid program are at the greatest risk. The difference in risks between day-care and home-care children, however, is reduced to an insignificant level for children older than 1.5 years of age and for children covered by the HMO health plan. Among day-care children, those who are covered by the Medicaid program are at a significantly higher risk than those who are covered by the HMO health plan. CONCLUSIONS: Although day-care children in general suffer a greater risk of common infectious diseases, the extent of day care effect on risks of diarrhoeal illness and URI varies significantly by age and type of health insurance plan.

Child Care↗
PubMed2002

Enhanced light confinement in a near-field optical probe with a triangular aperture.

We present a probe concept for scanning near-field optical microscopy combining the excellent background suppression of aperture probes with the superior light confinement of apertureless probes. A triangular aperture at the tip of a tetrahedral waveguide (full taper angle approximately 90 degrees ) shows a strong field enhancement at only one rim when illuminated with light of suitable polarization. Compared to a circular aperture of equivalent size, the resolution capability is doubled without loss of brightness. For a approximately 60 nm sized triangular aperture, we measured an optical resolution <40 nm and a transmission of approximately 10(-4).

Journal Article↗
PubMed2001

Targeted disruption of the murine Fanconi anemia gene, Fancg/Xrcc9.

Fanconi anemia (FA) is a human autosomal recessive cancer susceptibility disorder characterized by cellular sensitivity to mitomycin C and ionizing radiation. Six FA genes (corresponding to subtypes A, C, D2, E, F, and G) have been cloned, and the encoded FA proteins interact in a common cellular pathway. To further understand the in vivo role of one of these human genes (FANCG), we generated a targeted disruption of murine Fancg and bred mice homozygous for the targeted allele. Similar to the phenotype of the previously described Fancc(-/-) and Fanca(-/-) mice, the Fancg(-/-) mice had normal viability and no gross developmental abnormalities. Primary splenic lymphocytes, bone marrow progenitor cells, and murine embryo fibroblasts from the Fancg(-/-) mice demonstrated spontaneous chromosome breakage and increased sensitivity to mitomycin C and, to a lesser extent, ionizing radiation. Fancg(-/-) lymphocytes had a defect in the FA pathway, based on their failure to activate the monoubiquitination of the downstream Fancd2 protein in response to IR. Finally, Fancg(-/-) mice had decreased fertility and abnormal gonadal histology. In conclusion, disruption of the Fancg gene confirms the role of Fancg in the FA pathway. The Fancg(-/-) mouse may be useful as an animal model for future gene therapy and cancer susceptibility studies.

Alleles↗
PubMed2001

Conditional tissue-specific expression of the acid alpha-glucosidase (GAA) gene in the GAA knockout mice: implications for therapy.

Both enzyme replacement and gene therapy of lysosomal storage disorders rely on the receptor-mediated uptake of lysosomal enzymes secreted by cells, and for each lysosomal disorder it is necessary to select the correct cell type for recombinant enzyme production or for targeting gene therapy. For example, for the therapy of Pompe disease, a severe metabolic myopathy and cardiomyopathy caused by deficiency of acid alpha-glucosidase (GAA), skeletal muscle seems an obvious choice as a depot organ for local therapy and for the delivery of the recombinant enzyme into the systemic circulation. Using knockout mice with this disease and transgenes containing cDNA for the human enzyme under muscle or liver specific promoters controlled by tetracycline, we have demonstrated that the liver provided enzyme far more efficiently. The achievement of therapeutic levels with skeletal muscle transduction required the entire muscle mass to produce high levels of enzyme of which little found its way to the plasma, whereas liver, comprising <5% of body weight, secreted 100-fold more enzyme, all of which was in the active 110 kDa precursor form. Furthermore, using tetracycline regulation, we somatically induced human GAA in the knockout mice, and demonstrated that the skeletal and cardiac muscle pathology was completely reversible if the treatment was begun early.

Animals↗
PubMed2001

A functional role for Tsix transcription in blocking Xist RNA accumulation but not in X-chromosome choice.

In female mammals, up-regulation of Xist triggers X-chromosome inactivation in cis. Up-regulation is inhibited by sequences 3' to Xist contained within the antisense locus, Tsix. Inhibition could depend on transcription of Tsix and/or on DNA elements therein. Here we test the role of Tsix transcription by augmenting the duration and strength of Tsix expression. We find that Tsix hypertranscription is sufficient to block Xist RNA accumulation in a cis-limited manner. We propose that Tsix transcription is necessary to restrict Xist activity on the future active X and, conversely, that Tsix repression is required for Xist RNA accumulation on the future inactive X. We also find that Tsix hypertranscription does not affect X-chromosome choice. Thus, choice is mediated by elements within Tsix that are independent of promoter activity.

Animals↗
PubMed2001

Surprises of genetic engineering: a possible model of polyglucosan body disease.

BACKGROUND: The authors previously reported the generation of a knockout mouse model of Pompe disease caused by the inherited deficiency of lysosomal acid alpha-glucosidase (GAA). The disorder in the knockout mice (GAA-/-) resembles the human disease closely, except that the clinical symptoms develop late relative to the lifespan of the animals. In an attempt to accelerate the course of the disease in the knockouts, the authors increased the level of cytoplasmic glycogen by overexpressing glycogen synthase (GSase) or GlutI glucose transporter. METHODS: GAA-/- mice were crossed to transgenic mice overexpressing GSase or GlutI in skeletal muscle. RESULTS: Both transgenics on a GAA knockout background (GS/GAA-/- and GlutI/GAA-/-) developed a severe muscle wasting disorder with an early age at onset. This finding, however, is not the major focus of the study. Unexpectedly, the mice bearing the GSase transgene, but not those bearing the GlutI transgene, accumulated structurally abnormal polysaccharide (polyglucosan) similar to that observed in patients with Lafora disease, glycogenosis type IV, and glycogenosis type VII. Ultrastructurally, the periodic acid-Schiff (PAS)-positive polysaccharide inclusions were composed of short, amorphous, irregular branching filaments indistinguishable from classic polyglucosan bodies. The authors show here that increased level of GSase in the presence of normal glycogen branching enzyme (GBE) activity leads to polyglucosan accumulation. The authors have further shown that inactivation of lysosomal acid alpha-glucosidase in the knockout mice does not contribute to the process of polyglucosan formation. CONCLUSIONS: An imbalance between GSase and GBE activities is proposed as the mechanism involved in the production of polyglucosan bodies. The authors may have inadvertently created a "muscle polyglucosan disease" by simulating the mechanism for polyglucosan formation.

1,4-alpha-Glucan Branching Enzyme↗
PubMed2001

Identification and characterization of a tissue-specific silencer element in the first intron of the human acid maltase gene.

Deficiency of acid maltase (acid alpha-glucosidase), a lysosomal enzyme that degrades glycogen, results in glycogenosis type II, an autosomal recessive disease whose manifestations and severity largely depend on the level of residual enzyme activity. Previous studies have established that there are transcriptional control elements in the first intron; in particular a silencer responsive to Hes-1 and YY1 has been identified in the human hepatoma line, HepG2. This region functions as an enhancer in human fibroblasts. Here we have localized a silencer active in fibroblasts to a nearby 25-bp element in intron 1. This element repressed thymidine kinase promoter activity by about 50% in both orientations in human fibroblasts. This silencer, as with the previous one, is tissue specific since constructs containing this region are inactive in HepG2 cells. Electrophoretic mobility shift assay revealed three proteins specifically binding to the element in fibroblasts, and site-directed mutagenesis analysis indicated that all the three proteins binding to the element contribute to the silencer function. The data may be helpful for designing therapy to increase the level of enzyme, particularly when, as in most adults with the disease, there is reduced production of structurally normal enzyme.

Chloramphenicol O-Acetyltransferase↗
PubMed2001

[Changes in expression of angiotensin subtype AT1A and AT2 receptors in rats during cardiac remodeling following myocardial infarction].

Immunohistochemical and electron microscopic techniques and image analysis were employed to investigate the regulation of cardiac AT1A and AT2 subtype receptors in rats during cardiac remodeling following myocardial infarction (MI). Positive immunostaining for AT1A and AT2 receptors was observed in myocytes and vessels with AT1A being more than AT2. Three days after MI, disappearance of myocardial cross striation and fibroblast hyperplasia were found with electron microscopy. AT1A receptor protein expression in myocardial noninfarcted portion notably increased compared with that in sham-operated control rats (P < 0.001). No apparent changes were observed in AT2 receptor (P > 0.05). Two weeks after MI, myocyte cross striation and collagen deposition were found. Meanwhile, AT1A receptor staining decreased compared with that of three days after MI (P < 0.01), but there was still more than that of the control (P < 0.05). AT2 receptor was significantly increased compared with that of the sham-operated control rats (P < 0.001). These results suggest that both AT1A and AT2 receptor protein expression was upregulated in noninfarcted myocardium after MI, and the regulation of AT1A and AT2 receptors after MI may be involved in post-infarction cardiac remodeling.

Animals↗
PubMed2001

[Hunting for novel protein factors in G-protein pathway with yeast two-hybrid system].

OBJECTIVE: To explore the protein factors that could interact with G beta subunit within the G protein signal transducing pathway. METHODS: The highly sensitive protein-protein interaction system--Yeast Two-hybrid System was applied to screen the human cDNA library with constructed "Bite plasmid" containing G beta subunit gene fragment. And then the false positive test was adapted. RESULTS: Three positive gene fragments were obtained. One codes for "Actin bundling protein". The other two are new ones and their Gene Bank accession numbers are AF288405 and AF288406 respectively. CONCLUSIONS: It is the first time to find that among human brain tissue, G beta subunit becomes a structural or functional unit interacts with actin bundling protein and the other two unknown protein factors to activate the following pathway. This result may be important to understand the relationship between the actin cytoskeleton and G proteins.

Actins↗
PubMed2001

[Roles of G-protein beta and gamma subunits in the interaction of G beta gamma with adenylyl cyclases II].

OBJECTIVE: To explore the individual roles of G protein beta and gamma subunit in the interactions with effectors. METHODS: We investigated the interactions of G beta 1 and G beta 1 gamma 2 with adenylyl cyclase II(AC II) using the yeast two-hybrid and three-hybrid systems. RESULTS: When assayed for the abilities to activate the reporter gene, the interactions among AD-beta 1, gamma 2 and BD-AC IIQ in the three-hybrid system were more potent than the interactions between AD-beta 1 and BD-AC II Q in the two-hybrid system. The expressions of BD-AC IIQ and AD-beta 1 in transformants coexpressed AD-beta 1 and BD-AC IIQ, and transformants coexpressed AD-beta 1, gamma 2 and BD-AC IIQ were respectively detected. The comparisons between the reporter activity and the expression levels of BD-AC IIQ and AD-beta 1 in the yeast cells show there was no correlations, i.e. The difference in the reporter activity was not a reflection of differential expression level of the hybrid proteins. CONCLUSIONS: All these results suggest that G protein beta 1 subunit is sufficient to maintain the basic interaction between G beta 1 gamma 2 and AC IIQ, and gamma 2 subunit plays an important role in the high affinity interaction of G beta 1 gamma 2 with AC IIQ.

Adenylyl Cyclases↗