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Biomedical subjects

N Guo

Publications and source records attributed to N Guo.

At least 19 recordsLinked to original sources
PubMed2006

Pulsed Rayleigh wave scattered at a surface crack.

This paper investigates Rayleigh wave interaction with machined slots on flat aluminium blocks to simulate surface breaking cracks. Using a finite element method, Rayleigh wave scattering by narrow slots of varied depth ranging from 0.5 mm to 20 mm is calculated. Pulsed wideband Rayleigh waves with a centre frequency of 590 kHz and -6 dB bandwidth of 520 kHz is considered. Reflection and transmission coefficients are calculated and compare well with the published literature. We and other workers have reported enhancement of the measured amplitude or particle velocity of an apparent Rayleigh wave close to a surface defect. In this paper, it is found that the predicted enhancement of in-plane components of particle velocities close to a crack is significantly higher than that of the out-of-plane components of particle velocities which appears to be mainly due to the mode-converted surface skimming longitudinal wave from the crack that has mainly in-plane components near the sample surface. The enhancement of the in-plane particle velocity will be observed regardless of the type of in-plane sensitive ultrasonic detector used. The explanation of the discrepancy of the reflection and transmission coefficients obtained by pulsed and narrow band or pseudo continuous Rayleigh waves is discussed. The later-arriving Rayleigh waves from reverberation along the inside of the crack surface are observed, as has been previously reported by other workers, and this may also be used to gauge slot depth.

Journal Article↗
PubMed2005

The negative cell cycle regulator, Tob (transducer of ErbB-2), is a multifunctional protein involved in hippocampus-dependent learning and memory.

Tob (transducer of ErbB2) is a negative cell cycle regulator with anti-proliferative activity in the periphery. Using a behavioral screening paradigm to look for novel gene functions in the brain, we identified Tob as a brain-expressed protein involved in learning and memory. Behavioral training of fear-conditioning triggered a transient elevation of Tob protein, which preceded the formation of long-term memory. Functional perturbation of Tob by intra-CA1 infusion of antisense oligonucleotides in rats impaired spatial learning and memory in the Morris water maze and long-term memory for contextual fear conditioning, two behavioral paradigms that require the hippocampus. Furthermore, long-term potentiation was suppressed by Tob antisense infusion into the CA1 region. Together, these results indicate that the negative cell cycle regulator Tob is a multifunctional protein involved in hippocampus-dependent learning and memory.

Amino Acid Sequence↗
PubMed2005

Enhanced maturation and functional capacity of dendritic cells induced by mannosylated L2 domain of ErbB2 receptor.

The nature of antigens and functional state of dendritic cells (DC) are important in antigen presentation. The ability of DC for the induction of T-cell responses is promoted by maturation. It has been confirmed that mannose receptors mediate highly efficient endocytosis and presentation of mannosylated proteins. In the present study, L2 domain of ErbB2 ectodomain was expressed in Escherichia coli, purified and mannosylated. The maturation and functional capacity of DC induced by mannosylated L2 (mL2) protein were investigated. The results showed that L2 protein could induce DC maturation, which was accompanied by elevated expression of MHC and co-stimulatory molecules. The effect of mL2 protein on DC maturation was more remarkable than that of non-mL2 proteins. Uptake of mL2 antigens by DC was more efficient. Furthermore, the T cells can be stimulated to proliferate in vitro and secrete Th1 and Th2 cytokines. Higher levels of both IFN-gamma and IL-10 were detected from the T cells stimulated by mL2-pulsed DC, suggesting a concurrent activation of CD4+ and CD8+ T cells. The results demonstrated that L2 domain of ErbB2 receptor is an immunodominant molecule. The mL2 domain of ErbB2 can induce an enhanced maturation and functional capacity of DC. It may become an effective strategy to induce anti-ErbB2 response.

Antigen Presentation↗
PubMed2004

Structural analysis of the epitopes on erbB2 interacted with inhibitory or non-inhibitory monoclonal antibodies.

erbB2 oncogene encodes a growth factor receptor. The overexpression of erbB2 was correlated with more aggressive tumors and a poorer prognosis. Some antibodies directed to this molecule have an antitumor effect in vivo, but some antibodies do not. In an attempt to understand the molecular basis of the anti-erbB2 antibody interaction with erbB2 ectodomain (ECD), we analyzed binding epitopes on erbB2 for inhibitory and non-inhibitory antibodies, Herceptin and HF by computer-guided protein engineering and site-directed mutagenesis. Two different interaction domains were identified by molecular docking, computer graphics and distance geometry method and confirmed through studies on a series of mutants of erbB2 ECD. Non-inhibitory antibody HF only recognized N-terminal portion of erbB2 ECD, but inhibitory antibody Herceptin bound to C-terminal portion of it exclusively. The region interacted with inhibitory antibody Herceptin can be an important target for anticancer therapies.

Antibodies, Monoclonal↗
PubMed2001

[Allogeneic peripheral blood stem cell transplantation for high-risk leukemia].

OBJECTIVE: To study the effects of allogeneic peripheral blood stem cell transplantation (allo-PBSCT) in high-risk leukemia. METHODS: From October 1995 to December 2000, 25 patients with high-risk leukemia (median age 34 years, range 5.5-52 years) were transplanted with peripheral blood stem cells from their HLA-identical sibling donors. Among them, 15 patients suffered from acute leukemia (ALL) (one ph+ ALL in CR1, seven in CR2 or greater, and seven in relapse, including two in relapse after the first all-BMT), four patients suffered from chronic myelocytic leukemia (CML) (in CP2, AP, BC, and relapse after BMT respecively), 6 patients suffered from myelodys plastic syndrome (MDS), including one case of refractory anemia with excess of blasts (REAB), one case of refractory anemia with excess of blasts in trransformation (REAB-T), and 4 cases of acute leukemia secondary to MDS. The graft versus host disease (GVHD) prophylaxis included administration of cyclosporine and methotrexate. RESULTS: All patients were successfully engrafted. The median times (range) for their neutrophil returning to > or = 0.5 x 10(9)/L and for platelet returning to > or = 20 x 10(9)/L were 14 (10-18) days and 11 (7-45) days after transplantation resprctively. Grade II acute GVHD occurred in 12 patients with an incidence rate of 48%. Grade III GVHD was found in one patient (4%). No grade IV GVHD was seen. Among the 23 evaluable patients, 16 were diagnosed as chronic GVHD (70%). The actual transplant-related mortality was 16%. Leukemia relapse occurred in 6 patients, four of them received donor lymphocyte infusion (DLI) and achieved remission again. Nineteen patients were alive and disease-free with a median follow-up time of 304 (94-1,963) days. The two-year probability of overall survival, disease-free survival (DFS), and relapse rates were 64%, 58%, and 25% respectively. CONCLUSION: Allo-PBSCT decreases the relapse rate, increases the disease-free survival rate for patients with high-risk leukemia. All-PBSCT may be a better choice for patients with high-risk hematological maligmancies.

Adolescent↗
PubMed2001

Conformational regulation of the fibronectin binding and alpha 3beta 1 integrin-mediated adhesive activities of thrombospondin-1.

The recognition of extracellular matrix components can be regulated by conformational changes that alter the activity of cell surface integrins. We now demonstrate that conformational regulation of the matrix glycoprotein thrombospondin-1 (TSP1) can also modulate its binding to an integrin receptor. F18 1G8 is a conformation-sensitive TSP1 antibody that binds weakly to soluble TSP1 in the presence of divalent cations. However, binding of the antibody to melanoma cells was strongly stimulated by adding exogenous TSP1 in the presence of calcium, suggesting that TSP1 undergoes a conformational change following its binding to the cell surface. This conformation was not induced by known cell surface TSP1 receptors, whereas binding of F18 was stimulated when TSP1 bound to fibronectin but not to heparin or fibrinogen. Conversely, binding of F18 to TSP1 enhanced TSP1 binding to fibronectin. Exogenous fibronectin also stimulated TSP1-dependent binding of F18 to melanoma cells. Binding of the fibronectin-TSP1 complex to melanoma cells was mediated by alpha4beta1 and alpha5beta1 integrins. Furthermore, binding to F18 or fibronectin strongly enhanced the adhesive activity of immobilized TSP1 for some cell types. This enhancement of adhesion was mediated by alpha3beta1 integrin and required that the alpha3beta1 integrin be in an active state. Fibronectin also enhanced TSP1 binding to purified alpha3beta1 integrin. Therefore, both fibronectin and the F18 antibody induce conformational changes in TSP1 that enhance the ability of TSP1 to be recognized by alpha3beta1 integrin. The conformational and functional regulation of TSP1 activity by fibronectin represents a novel mechanism for extracellular signal transduction.

Animals↗
PubMed2001

The human gC1qR/p32 gene, C1qBP. Genomic organization and promoter analysis.

gC1qR is an ubiquitously expressed cell protein that interacts with the globular heads of C1q (gC1q) and many other ligands. In this study, the 7.8-kilobase pair (kb) human gC1qR/p32 (C1qBP) gene was cloned and found to consist of 6 exons and 5 introns. Analysis of a 1.3-kb DNA fragment at the 5'-flanking region of this gene revealed the presence of multiple TATA, CCAAT, and Sp1 binding sites. Luciferase reporter assays performed in different human cell lines demonstrated that the reporter gene was ubiquitously driven by this 1.3-kb fragment. Subsequent 5' and 3' deletion of this fragment confined promoter elements to within 400 base pairs (bp) upstream of the translational start site. Because the removal of the 8-bp consensus TATATATA at -399 to -406 and CCAAT at -410 to -414 did not significantly affect the transcription efficiency of the promoter, GC-rich sequences between this TATA box and the translation start site may be very important for the promoter activity of the C1qBP gene. One of seven GC-rich sequences in this region binds specifically to PANC-1 nuclear extracts, and the transcription factor Sp1 was shown to bind to this GC-rich sequence by the supershift assay. Primer extension analysis mapped three major transcription start regions. The farthest transcription start site is 49 bp upstream of the ATG translation initiation codon and is in close proximity of the specific SP1 binding site.

3' Untranslated Regions↗
PubMed2001

Desiccation tolerance in human cells.

The ability to desiccate mammalian cells while maintaining a high degree of viability would have implications for many areas of biological science, including tissue engineering. Previously, we reported that introduction of the genes for trehalose biosynthesis allowed human cells in culture to be reversibly desiccated for up to 5 days. Here, we have further investigated the factors that allow human cells to survive in the desiccated state. The most important finding is that vacuum greatly enhances the ability of human cells in culture to withstand desiccation. In fact, cells dried slowly and stored under vacuum are able to withstand desiccation even in the absence of added carbohydrates or polyols. In addition to vacuum, the rate of desiccation, the temperature at which cells are maintained, the degree of confluence when dried, and the presence or absence of light have a large effect on the ability to retain viability in the desiccated state. Our data are consistent with a model in which cells can retain viability if they are desiccated in such a way that cellular structures are maintained. However, gradual loss of viability may be due to damage that occurs over time in the desiccated state, perhaps due to free radicals. Further optimization of the process for desiccating and maintaining cells is required before long-term storage of desiccated cells can be achieved.

Carbohydrates↗
PubMed2001

[Cytomegalovirus enteritis in recipients of allogeneic peripheral blood stem cell transplantation].

OBJECTIVE: To report 6 cases of cytomeganlovirus (CMV) enteritis in allogeneic bone marrow transplantation (allo-BMT) or peripheral blood stem cell transplantation(PBSCT) recipients and the outcome after treatment. METHODS: The 6 patients suffered from leukemia and received allo-BMT or allo-PBSCT. RESULTS: Five of the 6 patients had acute GVHD II-III at 42, 26, 66, 45 and 57 days after transplantation respectively and they recovered after proper treatment. However they soon had severe diarrhea, abdominal pain or/and gastrointestinal bleeding, 5 of the 6 patients received endoscopic examination with biopsy at 50, 57, 80, 65, 35 days after transplantation respectively. They were all diagnosed as having CMV enteritis based on the presence of cytomegalic cells on mucosal biopsy specimens stained with hematoxylin and eosin. Meanwhile the immunoperoxidase stain of histologic specimens for CMV antigen or in situ hybridization by CMV DNA probe was positive. One patient was diagnosed CMV enteritis at 138 days after transplantation based on the clinic and response to therapy. They received antiviral treatment with ganciclovir (DHPG) 500 mg/d for 4 to 21 days, foscarnet 2.4 g q8 h or 4.8 g q12 h for 21 to 90 days, garlic extract 60-120 mg/d, globulin and other supportive measures. All the 6 cases had complete clinical response. CONCLUSION: CMV enteritis should be diagnosed as soon as possible with histopathologic examination and early proper treatment may lead to good clinical response.

Adult↗
PubMed2001

Epidemiological study of pathogenic fungi in China: 1986 and 1996.

OBJECTIVE: An annual decade epidemiological survey of pathogenic fungi of inpatients or outpatients includes more than 25 provinces in China has been done in 1986 and 1996. METHODS: In 1986, there were a total of 9096 strains of pathogenic fungi collected from more than 41 units of 25 provinces in China. 10 years late, 18,085 strains of pathogenic fungi from 41 units of 25 provinces were collected from January 1st to December 31st in 1996. RESULTS: The results showed that during this decade the prominent pathogenic fungus was Trichophyton rubrum, but its ratio gradually decreased. On the contrary, Candida albicans gradually increased in its ratio from 5th in 1986 to 2nd in 1996. CONCLUSION: The pathogenic fungi in China have changed greatly in the past decade from 1986 to 1996.

Candida albicans↗
PubMed2001

[Effect of interferon-alpha on the prognosis of bone marrow transplantation in chronic myeloid leukemia].

OBJECTIVE: To investigate whether prior interferon alfa (IFN-alpha) treatment affects the outcome of allogeneic bone marrow transplantation. METHODS: The outcome of 85 patients with chronic myelogenous leukemia (CML) in first chronic phase received transplants from an HLA-identical sibling donor was analyzed. Of the 85 patients, 30 did not receive IFN-alpha, whereas 30, 15 and 10 patients received IFN-alpha 3 x 10(6) units 3-4 times per week for < 6, 6-12 and > 12 months before transplant combined with hydroxyurea and/or HA regimen (H: Harringtonine; A: Ara-C) respectively. RESULTS: Pretransplant IFN-alpha therapy for > or = 6 months was associated with an increased risk of severe (grade III-IV) acute graft-versus-host disease (GVHD) (P < 0.01) as compared to that in < 6 months or no IFN-alpha therapy. No influence of pretransplant IFN-alpha treatment on engraft, cGVHD, VOD, relapse and TRM (transplant-related mortality) was found. Survival rate of IFN-alpha therapy < 6 months group (90.0%) was higher than that of no IFN-alpha group (68.9%) or > 12 months group(60.0%) (P < 0.05). CONCLUSION: It was found that there was a trend towards an improved survival in the IFN-alpha < 6 months group. Pretransplant IFN-alpha therapy for > or = 6 months was associated with an increased risk of severe aGVHD.

Adolescent↗
PubMed2001

[Relationship between soluble Fas ligand levels and complications after allogeneic bone marrow transplantation].

OBJECTIVE: To evaluate the implications of soluble Fas ligand (sFasL) in acute graft-versus-host disease (aGVHD) and discriminating symptoms of aGVHD from those of infection. METHODS: Plasma levels of sFasL were assessed in 84 plasma samples from 13 patients after allogeneic BMT using a sandwich enzyme-linked immunological assay (ELISA). Plasma sFasL levels of the patients before BMT and at different time points in the post-BMT period were measured. The results were analysed for correlation with aGVHD and infections. RESULTS: Plasma sFasL levels were significantly higher in patients with grade II - IV aGVHD than that in those with grade 0 - I aGVHD (P = 0.02). There was no statistic difference in plasma sFasL levels between the infectious and non-infectious patients. In the seven grade II - IV aGVHD patients, the plasma sFasL levels pre-BMT were much lower than that in the six grade 0 - I aGVHD patients. CONCLUSIONS: sFasL may be useful for the diagnosis of aGVHD and for differentiating aGVHD from other BMT related complications. The high level of plasma sFasL pre-BMT may be of importance in decreasing the occurrence of aGVHD after BMT.

Adolescent↗
PubMed2001

[An exploration of animal behavior screen platform for novel gene function in central nervous system].

For the purpose of large-scale screening of novel gene functions in mammalian nervous system, we have developed an animal behavior-monitoring platform employing antisense-oligo technology. Twenty genes of different categories were chosen from a low abundant gene (c)DNA sub-library of rat brain. Antisense oligo-nucleotides of these genes were designed and synthesized according to the homologues of the genes in mouse for mouse behavior tests. These antisense oligos were injected into the lateral ventricles of mouse brain using a Hamilton micro-syringe, with saline and oligos of scramble sequences as controls. These mice were tested with the following behavior model paradigms: metabolism, open field behavior, tail flick latency, and step-down test. Out of the 20 genes tested, 14 genes showed significant behavioral differences from the control groups at the level of P value less than 0.05 or 0.001 in different behavior animal models.

Animals↗
PubMed2001

[Detection of TTV DNA and TTV IgG in 328 serum samples].

OBJECTIVE: To investigate the prevalence of TT virus(TTV) in a variety of populations in China. METHODS: TTV DNA and anti TTV IgG were simultaneously tested by PCR and ELISA. RESULTS: The positive rate of TTV DNA in the samples of 81 normal subjects, 92 blood donors, 123 hepatitis A-G patients and 32 hepatitis non A-G patients were 2.5%, 2.2%, 19.5% and 28.1%, respectively; and anti-TTV IgG was 1.2%, 3.7%, 26.8% and 34.4%, respectively. There were significant differences between the normal and the blood donor group and the hepatitis group; and among multi-infectious cases, the infection rate of TTV with HBV was as high as 75.0%. CONCLUSION: The investigation indicated that TTV infection was very popular in different groups. Some of the normal and blood donor groups infected with TTV could become healthy carries of virus. And the hepatitis patients were the high risk group. In addition, TTV may be transmitted via other pathways besides blood.

Adult↗
PubMed2001

[Successful engraftment of HLA-identical sibling cord blood transplantation in an adult with chronic myelogenous leukemia].

OBJECTIVE: To explore the feasibility of cord blood transplantation (CBT) for the treatment of adult hematological malignancies and its long-term hematopoiesis reconstitution and transplantation-related complications. METHODS: An 18 years old patient (body weight 75 kg) with chronic myelogenous leukemia in first chronic phase received HLA-identical sibling CBT after conditioning with modified busulfan/cyclophosphamide (Bu/CTX) regimen. The transplanted number of nucleated cells was 1.73 x 10(7)/kg of body weight, and that of CD34+ cells 2. 7 x 10(5)/kg. Cyclosporin A and methylprednisolone were given as prophylaxis against graft versus-host disease (GVHD). RESULTS: The neutrophil count rose to above 0.5 x 10(9)/L on day 18 and platelet count exceeded 50 x 10(9)/L on day 36. Gene analysis showed that bone marrow cells had completely changed to donor's type on day 80. The patient was diagnosed with grade IV acute hepatic GVHD complicated with CMV infection because of severe jaundice on day 90. After the administration of additional immunosuppressive agents, antiviral agents, plasma exchange and in vitro billirubin adsorption, the complications were well controlled. In the follow-up of 24 months', the patient's general condition is good without obvious hepatic dysfunction and Ph chromosome and bcr/abl fusion gene of bone marrow cells were persistently negative. CONCLUSION: It is the first case reported in China that adult patient with leukemia has been successfully treated by allogeneic CBT, and this indicates that CBT is feasible in the treatment of adult patient with leukemia.

Adolescent↗
PubMed2000

An intronic downstream enhancer promotes 3' splice site usage of a neural cell-specific exon.

The human nonmuscle myosin heavy chain B gene contains a 30-nucleotide alternative exon, N30, that is included in the mRNA from neural cells but is skipped in all other cells. We have previously identified an intronic distal downstream enhancer (IDDE) region that is required for neural cell-specific inclusion of N30. In this study, we investigated the mechanism by which the IDDE promotes N30 exon usage. In vitro splicing analysis using neural cell nuclear extracts and two-exon pre-mRNA substrates, which consist of the N30 exon and either the upstream (E5) or downstream (E6) exon, demonstrates that the IDDE activates upstream E5-N30 splicing by facilitating early prespliceosome complex formation. The IDDE has no effect on N30-E6 splicing where the IDDE resides. Inspection of splice site consensus sequences shows that a polypyrimidine (Py) tract preceding N30 is suboptimal for U2AF binding. Optimizing the Py tract completely relieves the requirement for the IDDE in E5-N30 splicing in vitro. In transfected cells, the wild-type minigene transcripts, which consist of three exons, E5, N30, and E6, undergo neural cell-specific and IDDE-dependent alternative splicing of N30. Optimizing the Py tract in minigenes also completely relieves the requirement for the IDDE in N30 inclusion. Furthermore, overexpression of the truncated U2AF65, which contains the arginine and serine dipeptide-rich domain and linker domain, but lacks the RNA binding domain, selectively inhibits the IDDE-mediated N30 inclusion in mRNA from the wild-type minigene in a dominant negative fashion. These results support the hypothesis that the IDDE facilitates the recognition of the 3' splice site preceding N30 by a network of protein-protein interactions implicated in the recruitment of U2AF to a suboptimal Py tract.

Enhancer Elements, Genetic↗