Biomedical subjects

M Lu

Publications and source records attributed to M Lu.

At least 19 recordsLinked to original sources

PubMed2006

ADAMTS-13 levels in fresh, stored, and solvent detergent treated plasma.

BACKGROUND: ADAMTS-13 is implicated in the pathophysiology of thrombotic thrombocytopenic purpura (TTP). Plasma exchange is thought to be effective through removal of a harmful substance or provision of a required material such as ADAMTS-13. As various methods are used to prepare plasma we determined the effects of storage and solvent detergent treatment on the ADAMTS-13 levels in plasma. METHODS: Samples from fresh plasma and fresh frozen plasma (FFP) were stored at 22 degrees C and ADAMTS-13 levels were measured at 0, 12, 24, 48 and 72 h. Samples were also taken from solvent detergent treated plasma (SDP) and cryosupernatant plasma (CSP). Total protein, albumin, fibrinogen and immunoglobulins were also measured. RESULTS: In fresh plasma, the levels of both the 175 and 140 Kd subunits of von Willebrand factor were consistent at 1.38 and 1.35 OD units from 0 to 48 h indicating normal ADAMTS-13 activity. The Vitex SDP produced slightly more of the 140 Kd subunit than did Octapharma SDP which gave equivalent fragments. Cryosupernatant plasma was the same as normal plasma. None of these values changed over 48 h. There was a 28% decrease in FVIII in fresh plasma over 24 h. Fibrinogen and albumin were unchanged. CONCLUSION: ADAMTS-13 levels are not significantly decreased by storage of plasma at room temperature for up to 48 h. Both CSP and SDP also contained essentially normal levels of ADAMTS-13 and therefore could be used for treatment of patients with TTP.

ADAM Proteins↗

PubMed2006

A large-scale study on relationship between cerebral blood flow velocity and blood pressure in a natural population.

In order to verify the relationship between blood pressure and cerebral blood flow velocity in sub-clinical natural population, 1294 middle-aged and old Beijing rural residents were investigated in autumn 2002. For all subjects, systolic blood flow velocities (V(s)) in common carotid artery (CCA), internal carotid artery (ICA) and middle cerebral artery (MCA) were detected with trans-cranial Doppler. Key factors such as anthropometry, medication use, blood pressure and blood biochemical analysis were investigated at the same time. After controlling for age, gender, diabetes, hypercholesterolaemia, smoking and body mass index, multivariate analysis showed that systolic blood pressure (SBP) correlated positively with V(s) at MCA and slight negatively correlated with at CCA. As blood pressure rose by 10 mm Hg, the V(s) at MCA increased by 1.63 cm/s. Duration of hypertension (HD) negatively correlated with V(s) at MCA (P<0.01). The V(s) at MCA in early-stage and chronic hypertensive patients were 92.9+/-1.9 and 84.1+/-2.3 cm/s, respectively. Antihypertensive treatment could modify the V(s) at MCA towards a normal level by lowering blood pressure. In conclusion, the effect of hypertension on cerebral blood flow is complex. V(s) at MCA positively correlated with SBP, but negatively related to HD. Antihypertensive treatment might be helpful to keep cerebral blood flow at a normal level.

Adult↗

PubMed2006

Vascular endothelial growth factor mediates atorvastatin-induced mammalian achaete-scute homologue-1 gene expression and neuronal differentiation after stroke in retired breeder rats.

Neurogenesis declines with advancing age. The mammalian achaete-scute homologue-1 encodes a basic helix-loop-helix transcription factor, which controls neuronal differentiation. In this study, we first tested whether atorvastatin treatment enhances neurological functional outcome and neuronal differentiation after stroke in retired breeder 12 month rats. Rats were subjected to middle cerebral artery occlusion and treated with or without atorvastatin (3 mg/kg) for 7 days. Atorvastatin significantly increased expression of mammalian achaete-scute homologue-1, beta-tubulin III, and vascular endothelial growth factor in the ischemic brain, and concomitantly improved functional outcome compared with middle cerebral artery occlusion control rats. Increased neurogenesis significantly correlated with functional recovery after stroke. To further investigate the mechanisms of atorvastatin-induced neuronal differentiation, experiments were performed on neurospheres derived from retired breeder rat subventricular zone cells. Atorvastatin increased neuronal differentiation and upregulated vascular endothelial growth factor and mammalian achaete-scute homologue-1 gene expression in cultured neurospheres. Vascular endothelial growth factor-treated neurospheres significantly increased mammalian achaete-scute homologue-1 and beta-tubulin III expression. Inhibition of vascular endothelial growth factor decreased atorvastatin-induced mammalian achaete-scute homologue-1 and beta-tubulin III expression. These data indicate that atorvastatin increases neuronal differentiation in retired breeder rats. In addition, atorvastatin upregulation of vascular endothelial growth factor expression, influences mammalian achaete-scute homologue-1 transcription factor, which in turn, facilitates an increase in subventricular zone neuronal differentiation. These atorvastatin-mediated molecular events may contribute to the improved functional outcome in retired breeder rats subjected to stroke.

Analysis of Variance↗

PubMed2006

Classifying G protein-coupled receptors and nuclear receptors on the basis of protein power spectrum from fast Fourier transform.

As the potential drug targets, G-protein coupled receptors (GPCRs) and nuclear receptors (NRs) are the focuses in pharmaceutical research. It is of great practical significance to develop an automated and reliable method to facilitate the identification of novel receptors. In this study, a method of fast Fourier transform-based support vector machine was proposed to classify GPCRs and NRs from the hydrophobicity of proteins. The models for all the GPCR families and NR subfamilies were trained and validated using jackknife test and the results thus obtained are quite promising. Meanwhile, the performance of the method was evaluated on GPCR and NR independent datasets with good performance. The good results indicate the applicability of the method. Two web servers implementing the prediction are available at http://chem.scu.edu.cn/blast/Pred-GPCR and http://chem.scu.edu.cn/blast/Pred-NR.

Computer Simulation↗

PubMed2006

N-cadherin mediates nitric oxide-induced neurogenesis in young and retired breeder neurospheres.

Neurogenesis may contribute to functional recovery after neural injury. Nitric oxide donors such as DETA-NONOate promote functional recovery after stroke. However, the mechanisms underlying functional improvement have not been ascertained. We therefore investigated the effects of DETA-NONOate on neural progenitor/stem cell neurospheres derived from the subventricular zone from young and retired breeder rat brain. Subventricular zone cells were dissociated from normal young adult male Wistar rats (2-3 months old) and retired breeder rats (14 months old), treated with or without DETA-NONOate. Subventricular zone neurosphere formation, proliferation, telomerase activity, and Neurogenin 1 mRNA expression were significantly decreased and glial fibrillary acidic protein expression was significantly increased in subventricular zone neurospheres from retired breeder rats compared with young rats. Treatment of neurospheres with DETA-NONOate significantly decreased neurosphere formation and telomerase activity, and promoted neuronal differentiation and neurite outgrowth concomitantly with increased N-cadherin and beta-catenin mRNA expression in both young and old neurospheres. DETA-NONOate selectively increased Neurogenin 1 and decreased glial fibrillary acidic protein mRNA expression in retired breeder neurospheres. N-cadherin significantly increased Neurogenin 1 mRNA expression in young and old neurospheres. Anti-N-cadherin reversed DETA-NONOate-induced neurosphere adhesion, neuronal differentiation, neurite outgrowth, and beta-catenin mRNA expression. Our data indicate that age has a potent effect on the characteristics of subventricular zone neurospheres; neurospheres from young rats show significantly higher formation, proliferation and telomerase activity than older neurospheres. In contrast, older neurospheres exhibit significantly increased glial differentiation than young neurospheres. DETA-NONOate promotes neuronal differentiation and neurite outgrowth in both young and older neurospheres. The molecular mechanisms associated with the DETA-NONOate modulation of neurospheres from young and older animals as well age dependent effects of neurospheres appear to be controlled by N-cadherin and beta-catenin gene expression, which subsequently regulates the neuronal differentiating factor Neurogenin expression in both young and old neural progenitor cells.

Aging↗

PubMed2006

Polyethylene glycol (molecular weight 400 DA) vehicle improves gene expression of adenovirus mediated gene therapy.

PURPOSE: A significant limitation of adenoviral mediated suicide gene therapy is poor gene distribution in vivo. The choice of vehicle has been demonstrated to affect the level of adenoviral delivered gene transduction. We examined the hypotheses that 1) adenovirus suspended in PEG400 improves gene expression in the naïve canine prostate model, 2) improved transgene expression with PEG400 results in improved tumor control and 3) vehicle affects the initial adenoviral spread from a single intratumor injection. MATERIALS AND METHODS: The magnitude and volume of gene expression were measured 24 hours following intraprostatic injection of adenovirus suspended in PEG400 (12.5% weight per volume) or saline as vehicle. Tumor growth delay was measured in mice bearing human tumor xenografts following the injection of adenovirus in PEG400 and saline. The initial spread of adenovirus was measured by confocal microscopy following a single injection of fluorescently labeled adenoviral particles in human tumor xenografts using each vehicle. RESULTS: Adenovirus suspended in PEG400 provided an average of twice the level of gene expression in the canine prostate and significantly better tumor control relative to saline in preclinical tumor models (p = 0.046 and 0.036, respectively). The initial spread of adenovirus with PEG400 was superior to that of adenovirus in saline and the latter was largely limited to the needle tract. CONCLUSIONS: Adenoviral gene therapy vectors suspended in PEG400 results in improved tumor control because of greater initial adenoviral spread, and the increased volume and magnitude of gene expression in vivo.

Adenoviridae↗

PubMed2006

Prospective study of body size and risk for stroke amongst women below age 60.

The relation between obesity, particularly abdominal obesity, and risk of stroke amongst women remains unclear. In 1991-1992, a prospective study was initiated in Sweden amongst women who returned a self-administered questionnaire. Through linkage with nation-wide registries, 45,449 women, free of stroke at entry, were followed up until diagnosis of first incident stroke, death, or the end of follow-up in 2002. We estimated multivariate relative risks (RRs) with 95% confidence intervals (CIs) from Cox proportional hazards regression models. A total of 170 incident stroke cases occurred during an average of 11 years of follow-up. The RR of stroke amongst women in the highest compared with the lowest quintile was 2.4 (95% CI 1.3-4.2; P for trend 0.04) for waist-to-hip ratio, 2.5 (95% CI 1.5-4.3; P for trend 0.01) for waist-to-height ratio and 2.3 (95% CI 1.2-4.3; P for trend 0.02) for waist circumference. Adjustment for hypertension and diabetes attenuated these risk estimates. In contrast, birth weight, body mass index (BMI) at age 18, BMI at entry, weight change in adulthood and adult height were not significantly associated with risk of stroke. This study provides evidence that, in contrast to BMI, several different measures of abdominal obesity are strong predictors of stroke in women.

Adult↗

PubMed2006

The contribution of platelets in the production of cryoprecipitates for use in a fibrin glue.

BACKGROUND AND OBJECTIVES: Cryoprecipitate has a wide application for use as a fibrin glue. In some situations, platelets are added to the preparation in order to enhance the fibrin glue. MATERIALS AND METHODS: Fresh plasma was collected by apheresis from the same donor to produce 250 ml of platelet-rich plasma (PRP) or platelet-poor plasma (PPP) (n = 12 each). Cryoprecipitate was then produced following the standards of the American Association of Blood Banks and resuspended to a total volume of 8 ml, from which aliquots were removed and assayed. Clot formation was measured using the thromboelastogram. RESULTS: The protein content of the two preparations was identical for PRP and PPP. Results for fibrinogen (PPP 475 +/- 220 mg; PRP 399 +/- 215 mg), Factor VIII (PPP 186 +/- 67 IU; PRP 175 +/- 70 IU) and von Willebrand Factor (PPP 260 +/- 104 IU; PRP 221 +/- 88 IU) were not significantly different. The concentration of platelet-derived growth factor was markedly higher (a 100-fold increase at 3778 +/- 1036 ng) when platelets were added to the plasma. There was a small, but not statistically significant, difference in the rate of clot formation (R = 2.3 for PPP and 3.8 for PRP) and clot strength (MA = 63.4 for PPP and 56.6 for PRP) between PPP and PRP cryoprecipitates when measured using the thromboelastogram. CONCLUSIONS: Platelets do not significantly increase the concentration of the usual constituents of cryoprecipitate; however, the levels of platelet-derived growth factor are markedly enhanced. Therefore, there are advantages for using PRP to enhance the growth of new tissue.

Blood Platelets↗

PubMed2005

MRI-guided, open trial of abciximab for ischemic stroke within a 3- to 24-hour window.

The authors assessed the effect of IV abciximab on early neurologic improvement and ischemic lesion growth in 29 patients with supratentorial stroke and NIH stroke scale score (NIHSSS) > or = 4 (11.1 +/- 5.9), treated within 3 to 24 (13.6 +/- 5.5) hours of onset. The 48 to 72-hour NIHSSS improvement was 4.4 +/- 3.2 and the 24-hour lesion growth on DWI was +23% (-50%, +103%); 7/26 (27%) patients experienced lesion size decrease. Treatment of sub-24-hour stroke with abciximab improves early post-treatment neurologic status and often attenuates ischemic lesion growth.

Abciximab↗

PubMed2005

Identification of the pathological prion protein allotypes in scrapie-infected heterozygous bank voles (Clethrionomys glareolus) by high-performance liquid chromatography-mass spectrometry.

Cerebral formation of the pathological isoform of the prion protein (PrP) is a crucial molecular event in prion diseases. The bank vole (Clethrionomys glareolus) is a rodent species highly susceptible to natural scrapie. The PrP gene of bank vole is polymorphic (Met/Ile) at codon 109. Here we show that homozygous 109Met/Met voles have incubation times shorter than heterozygous 109Met/Ile voles after experimental challenge with three different scrapie isolates. An HPLC-MS/MS method was optimized and applied to investigate whether in heterozygous animals both PrP allotypes are able to undergo pathological conversion. The results demonstrate that both allotypes of the prion protein participate to pathological deposition.

Amino Acid Sequence↗

PubMed2005

Fluctuation of the cytokine expression in the liver during the chronic woodchuck hepatitis virus (WHV) infection is not related to viral load.

The woodchuck together with the woodchuck hepatitis virus (WHV) is an excellent model to study the pathogenesis of hepadnaviral infections. Chronic WHV infection causes severe liver disease and hepatocellular carcinoma in woodchucks. The mechanism of viral clearance is not fully understood, interferons seem to play a major role in down-regulating viral replication prior to elimination of infected hepatocytes. We investigated on the pattern of cytokine and T-cell-marker expression in livers of woodchucks chronically infected with WHV. RNase-protection-assay (RPA) was used to determine mRNA of woodchuck specific genes (TNF-alpha, IFN-gamma, IL-15, CD3, CD4, CD8). Serial liver biopsies were performed daily or weekly in eight chronic WHV-carrier woodchucks. Cytokine/T-cell-marker expression differed significantly between the time points up to +/-50% within each woodchuck. The different expression patterns of cytokines or T-cell-markers did not correlate to the (weak) fluctuations in the viremia but may explain the observed fluctuations in the WHV/HBV-load in chronically infected individuals. Furthermore, we observed associations between cytokine and T-cell-marker expression. The marginal fluctuations in viremia during the chronic infection may indicate, that, once the chronic hepadnaviral infection is established, cytokines/interferons expressed endogenously (i.e. not vector-borne or injected) play only a minor role.

Animals↗

PubMed2005

The genome of the social amoeba Dictyostelium discoideum.

The social amoebae are exceptional in their ability to alternate between unicellular and multicellular forms. Here we describe the genome of the best-studied member of this group, Dictyostelium discoideum. The gene-dense chromosomes of this organism encode approximately 12,500 predicted proteins, a high proportion of which have long, repetitive amino acid tracts. There are many genes for polyketide synthases and ABC transporters, suggesting an extensive secondary metabolism for producing and exporting small molecules. The genome is rich in complex repeats, one class of which is clustered and may serve as centromeres. Partial copies of the extrachromosomal ribosomal DNA (rDNA) element are found at the ends of each chromosome, suggesting a novel telomere structure and the use of a common mechanism to maintain both the rDNA and chromosomal termini. A proteome-based phylogeny shows that the amoebozoa diverged from the animal-fungal lineage after the plant-animal split, but Dictyostelium seems to have retained more of the diversity of the ancestral genome than have plants, animals or fungi.

ATP-Binding Cassette Transporters↗

PubMed2005

Exotic meson decay to omegapi0pi-.

A partial-wave analysis of the mesons from the reaction pi(-)p --> pi(+)pi(-)pi(-)pi(0)pi(0)p has been performed. The data show b(1)pi decay of the spin-exotic states pi(1)(1600) and pi(1)(2000). Three isovector 2(-+) states were seen in the omegarho(-) decay channel. In addition to the well known pi(2)(1670), signals were also observed for pi(2)(1880) and pi(2)(1970).

Journal Article↗

PubMed2005

[Diverticula of the appendix and their complications: value of sonography (review of 21 cases)].

PURPOSE: Diverticulosis is defined by the presence of diverticula along any segment of the GI tract. Diverticulosis and its associated complications may involve the appendix. The imaging and histological findings of 21 cases of diverticulitis of the appendix are reviewed. MATERIALS AND METHODS: Sonography, because of its high spatial resolution, is an ideal imaging technique to diagnose diverticulitis of the appendix. RESULTS: Similar to diverticulosis of the large bowel, diverticula of the appendix correspond to pseudo-diverticula composed of mucosa and sub mucosa herniating through the muscular layer. Chronic inflammatory changes affect the surrounding appendicular wall, as confirmed by histological examination. Clinical symptoms range from chronic right lower quadrant abdominal pain to acute appendicitis and even peritonitis. CONCLUSION: Based on this retrospective analysis of 21 cases, it is possible to describe the specific and sensitive imaging findings for diagnosis of simple and complicated forms of diverticulitis of the appendix. Surgery is the treatment of choice because of the high risk of perforation.

Appendix↗

PubMed2005

The recombinant rat glucagon-like peptide-1 receptor, expressed in an alpha-cell line, is coupled to adenylyl cyclase activation and intracellular calcium release.

The glucagon-like peptide-1 (GLP-1) receptor is expressed on alpha-cells, though its functional significance is unknown. The endogenous beta-cell GLP-1 receptor is coupled to adenylyl cyclase, cell depolarization, activation of voltage-dependent Ca2+ channels (VDCC) and extracellular Ca2+ influx (Lu et al., 1993 b). In contrast, the signaling pathways of the GLP-1 receptor in alpha-cells are poorly understood. To determine the signaling mechanisms of the alpha-cell GLP-1 receptor, we established a stable pancreatic islet alpha-cell line expressing the recombinant rat GLP-1 receptor (INR1-SF2), using INRl-G9 cells. These INRl-G9 cells do not express endogenous GLP-1 receptor. In INR1-SF2 cells, GLP-1 bound to the recombinant receptor (Kd = 0.9 nM) and increased cAMP (ED50 = 0.6 nM). GLP-1 increased the free cytosolic Ca2+ ([Ca2+]i) (ED50 = 50 nM) by release from intracellular stores, but did not affect INR1-SF2 cell phosphoinositol turnover. Despite expressing VDCC, the INR1-SF2 cells were not depolarized by GLP-1, even in the presence of glucose. This contrasts with the depolarizing action of GLP-1 in beta-cells in the presence of glucose (Lu et al., 1993 b). This study establishes that a single GLP-1 receptor species can mediate the effects of GLP-1 through multiple signaling pathways, including the adenylyl cyclase system and intracellular Ca2+ release, in an alpha-cell type. Furthermore, since GLP-1 is unable to cause cellular depolarization or activate VDCC in INR1-SF2 cells, these data suggest that glucose-induced membrane depolarization may be crucial for GLP-1 to further activate VDCC and potentiate glucose-stimulated insulin release in beta-cells. Finally this study describes a cell line that can be used as a model system for evaluation of GLP-1 signaling in alpha-cells.

Adenylyl Cyclases↗

PubMed2004

Quantitative assessment of early healing of intramembranous and endochondral autogenous bone grafts using micro-computed tomography and Q-win image analyzer.

Micro-computed tomography (microCT) is a new tool to image and quantify trabecular bone. The aim of this study is to compare the two measurement methods when evaluating the early healing of intramembranous (IM) and endochondral (EC) autogenous bone grafts using micro-computed tomography and Q-win computer image analyzer. Twelve critical size (15 mm x 10 mm) defects were created in rabbit mandibles bilaterally. Six defects were grafted with autogenous EC bone; six defects were grafted with autogenous IM bone. Three weeks post-surgery, the defects were retrieved for microCT imaging analysis and histological evaluation. Results showed a significant correlation (r = 0.96, P < 0.0001) between microCT and Q-win in measuring the volume of new bone and graft bone in the mandibular defects after 3 weeks of early healing. There were distinct differences between IM bone and EC bone grafts in 2D and 3D features of graft bone maintenance as well as new bone formation. MicroCT imaging is a non-destructive, fast and precise procedure that allows for quantitative evaluation of the early healing of IM and EC autogenous bone grafts in membranous bone defects.

Analysis of Variance↗

PubMed2004

Identification of a glycosylation site in the woodchuck hepatitis virus preS2 protein and its role in protein trafficking.

The middle surface antigen (M-sAg) of hepadnaviruses is one of three envelope proteins that share a common C-terminal S domain. M-sAg contains the preS2 domain in addition to the S region. The preS2 region of woodchuck hepatitis virus (WHV) contains a potential glycosylation site Asn-Gln-Thr at amino acid (aa) positions 3-5. In this study, we mutated this site by site-directed mutagenesis and confirmed that glycosylation occurs here. In in vitro translation assays, the mutation Thr to Asn at aa 5 significantly impaired glycosylation of M-sAg. The mutated M-sAg formed abnormal clustered structures in transfected cells as determined by immunofluorescent staining. Confocal microscopic analysis showed that an enrichment of this glycosylation-deficient protein in the Golgi apparatus occurred, which is not typical for the wild-type protein. These results are consistent with earlier findings that incorrect glycosylation of viral proteins may interfere with virus assembly.

Amino Acid Sequence↗

PubMed2003

Interstitial collagenase activity stimulates the formation of actin rings and ruffled membranes in mouse marrow osteoclasts.

Interstitial collagenase activity stimulates bone resorption by mouse marrow osteoclasts [1]. Here, we show that collagenase activity promotes bone resorption by activating adherent osteoclasts to resorb bone. Inhibition of interstitial collagenase activity, either with peptidomimetic hydroxymates or with a specific anti-interstitial collagenase inhibiting antibody, reduced bone resorption by 73-92%. Equal numbers of osteoclasts adhered to bone in the presence of collagenase inhibitors and osteoclast survival was unaffected. In contrast, formation of actin rings and polarization of the vacuolar-H+-ATPase (V-ATPase) to ruffled membranes, two indicators of osteoclast activation, were decreased by inhibiting collagenase activity and stimulated in the presence of cleaved or heat-denatured type I collagen in proportion to increases and decreases of bone resorptive activity. Addition of excess recombinant osteoprotegerin-ligand to cultures did not restore bone resorption in the presence of interstitial collagenase inhibitors. These data support the hypothesis that cleaved collagen stimulates osteoclastic bone resorption by triggering cytoskeletal reorganization and transport of V-ATPase from cytoplasmic stores to ruffled membranes.

Actins↗