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Na Li

Publications and source records attributed to Na Li.

At least 109 records · Page 6Linked to original sources
PubMed2004

Evidence for substantial fine-scale variation in recombination rates across the human genome.

Characterizing fine-scale variation in human recombination rates is important, both to deepen understanding of the recombination process and to aid the design of disease association studies. Current genetic maps show that rates vary on a megabase scale, but studying finer-scale variation using pedigrees is difficult. Sperm-typing experiments have characterized regions where crossovers cluster into 1-2-kb hot spots, but technical difficulties limit the number of studies. An alternative is to use population variation to infer fine-scale characteristics of the recombination process. Several surveys reported 'block-like' patterns of diversity, which may reflect fine-scale recombination rate variation, but limitations of available methods made this impossible to assess. Here, we applied a new statistical method, which overcomes these limitations, to infer patterns of fine-scale recombination rate variation in 74 genes. We found extensive rate variation both within and among genes. In particular, recombination hot spots are a common feature of the human genome: 47% (35 of 74) of genes showed substantive evidence for a hot spot, and many more showed evidence for some rate variation. No primary sequence characteristics are consistently associated with precise hot-spot location, although G+C content and nucleotide diversity are correlated with local recombination rate.

Genome, Human↗
PubMed2004

Modified heparin inhibits P-selectin-mediated cell adhesion of human colon carcinoma cells to immobilized platelets under dynamic flow conditions.

Accumulating evidence indicates that the formation of tumor cell platelet emboli complexes in the blood stream is a very important step during metastases and that the anti-metastasis effects of heparin are partially due to a blockade of P-selectin on platelets. In this study, heparin and chemically modified heparins were tested as inhibitors of three human colon carcinoma cell lines (COLO320, LS174T, and CW-2) binding to P-selectin, adhering to CHO cells expressing a transfected human P-selectin cDNA, and adhering to surface-anchored platelets expressing P-selectin under static and flow conditions. The aim was to screen for heparin derivatives with high anti-adhesion activity but negligible anticoagulant activity. In this study, four modified heparins with high anti-adhesion activity were identified including RO-heparin, CR-heparin, 2/3ODS-heparin, and N/2/3DS-heparin. NMR analysis proved the reliability of structure of the four modified heparins. Our findings suggested that the 6-O-sulfate group of glucosamine units in heparin is critical for the inhibition of P-selectin-mediated tumor cell adhesion. Heparan sulfate-like proteoglycans on these tumor cell surfaces are implicated in adhesion of the tumor cells to P-selectin. Some chemically modified heparins with low anticoagulant activities, such as 2/3ODS-heparin, may have potential value as therapeutic agents that block P-selectin-mediated cell adhesion and prevent tumor metastasis.

Animals↗
PubMed2004

Characterization of hemoglobin immobilized on gamma-zirconium phosphate.

The fact that different gamma-zirconium phosphate (gamma-ZrP) preintercalation method induced varied degree and type of conformational change of the adsorption protein was confirmed by characterization techniques including circular dichroism (CD), fourier transform infrared spectroscopy (FTIR) and X-ray powder diffraction (XRD) analysis. The results indicated that the association of hemoglobin with gamma-ZrP preintercalated using butylamine was correlated with conformational change in the secondary structure of the protein. gamma-ZrP which was preintercalated with tetra (n-butylammonium) hydroxide caused the conformational change of Hemoglobin in both the secondary structure and the tertiary structure. X-ray powder diffraction analysis was used to analyze the crystalline structure of the nanocomposites prepared by relamination. The adsorption isotherms of Hemoglobin on different matrices were set up and fitted with Langmuir and Freundlich equations.

Absorption↗
PubMed2004

Gain-of-function polymorphism in mouse and human Ltk: implications for the pathogenesis of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE), a complex multigenic disease, is a typical antibody-mediated autoimmune disease characterized by production of autoantibodies against a variety of autoantigens and immune complex-type tissue inflammation, most prominently in the kidney. Evidence suggests that genetic factors predisposing to aberrant proliferation/maturation of self-reactive B cells initiate and propagate the disease. In SLE-prone New Zealand Black (NZB) mice and their F1 cross with New Zealand White (NZW) mice, B cell abnormalities can be ascribed mainly to self-reactive CD5+ B1 cells. Our genome-wide scans to search for susceptibility genes for aberrant activation of B1 cells in these mice showed evidence that the gene, Ltk, encoding leukocyte tyrosine kinase (LTK), is a possible candidate. LTK is a receptor-type protein tyrosine kinase, belonging to the insulin receptor superfamily, and is mainly expressed in B lymphocyte precursors and neuronal tissues. Sequence and functional analyses of the gene revealed that NZB has a gain-of-function polymorphism in the LTK kinase domain near YXXM, a binding motif of the p85 subunit of phosphatidylinositol 3-kinase (PI3K). SLE patients also had this type of Ltk polymorphism with a significantly higher frequency compared with the healthy controls. Our findings suggest that these polymorphic LTKs cause up-regulation of the PI3K pathway and possibly form one genetic component of susceptibility to abnormal proliferation of self-reactive B cells in SLE.

Adult↗
PubMed2004

Microvascular responses to adenosine help explain functional and pathologic differences between intestinal segments.

BACKGROUND: Many physiologic (post-prandial hyperemia), pathologic (inflammatory bowel disease), and clinical (enteral feeding) phenomena involve changes in microvascular blood flow to the intestine. Adenosine (Ado) derived from energy metabolism causes vasodilation and appears to be involved in some of these events. The Ado-mediated control mechanisms appear to vary with the diameter of the microvessels and the function of the tissue. This suggests the possibility that Ado-based microvascular control varies between anatomic intestinal segments and microvascular levels in those intestinal segments. METHODS: In vivo digital intravital microscopy was used to measure the responses of larger distributing (A1) and smaller premucosal (A3) vessels to Ado in intact neurovascular loops of jejunum and terminal ileum of the rat. Dose-response curves to Ado were determined. RESULTS: Microvascular dilation and augmented blood flow to Ado were significantly greater in the jejunum than in the terminal ileum. Ado-induced dilation was greater in the smaller A3 than in the larger A1 microvessels. DISCUSSION: These data indicate (1) different vasodilator mechanisms for the jejunum and the terminal ileum, (2) a greater role for Ado-related microvascular control in the jejunum compared with the ileum, and (3) a greater Ado-related control in the premucosal (A3) vessels. These findings suggest that Ado-mediated microvascular effects could explain why some clinical phenomena vary in intensity in selective intestinal segments, and are likely to involve different microvascular control mechanisms in the different segments. Knowledge of these Ado mechanisms could be beneficial in certain clinical scenarios to control blood flow during pathologic conditions.

Adenosine↗
PubMed2004

Spectroscopic study on the interaction between methylene blue and chondroitin 4-sulfate and its analytical application.

The interaction of Methylene Blue (MB) with chondroitin-4-sulfate (CHS) has been investigated using spectroscopic techniques, including UV-Vis absorption, Rayleigh resonance scattering (RRS), and circular dichroism (CD). The addition of CHS caused a decrease in the absorbance of MB at 664 nm with a new absorption band appearing at 570 nm, enhanced RRS at 314 nm and 560 nm, and also resulted in an intense CD signal at 568 nm. The Scatchard model has been applied to calculating the binding constant and the number of binding sites. The calculated parameters are consistent with the experimental results. The factors affecting the interaction were investigated. Quantitative spectroscopic methods were developed for the first time. They are based on the fact that a decrease in the absorption at 664 nm and an enhancement of the RRS intensity at 314 nm are proportional to the concentration of CHS added in a certain range. Satisfactory results were obtained on the determination of synthetic samples.

Journal Article↗
PubMed2004

Angiotensin II stimulates phosphorylation of 4E-binding protein 1 and p70 S6 kinase in cultured vascular smooth muscle cells.

AIM: To examine the regulatory effects of angiotensin II (Ang II) on the phosphorylation of 4E-binding protein 1 (4E-BP1) and p70 S6 kinase in cultured vascular smooth muscle cells (VSMC), and the contribution of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB) signaling pathway in this process. METHODS: VSMC obtained from rat thoracic aortas were cultured. The phosphorylation of 4E-BP1 and p70 S6 kinase was detected by immunoblotting. RESULTS: Ang II significantly increased the phosphorylation of 4E-BP1 and p70 S6 kinase, with the peaks occurring at, respectively, 10 min and 30 min, after stimulation with Ang II. The stimulatory effect of Ang II on 4E-BP1 and p70 S6 kinase phosphorylation was abrogated by Ang II type 1 receptor (A(T1) receptor) antagonist losartan, and suppressed by PI3K inhibitor LY294002 in a concentration-dependent manner. CONCLUSION: Ang II treatment of VSMC induces the phosphorylation of 4E-BP1 and p70 S6 kinase via A(T1) receptor, and PI3K signaling pathway is involved in this process.

Angiotensin II↗
PubMed2004

[Obstructive sleep apnea syndrome and hypothyroidism (a report of three cases)].

OBJECTIVE: To explore the relationship between obstructive sleep apnea syndrome (OSAS) and hypothyroidism, and to discuss the management experience. METHOD: Three cases of severity OSAS with hypothyroidism were reported and relevant literatures were reviewed. One patient underwent continuous positive airway pressure (CPAP), one patient was performed uvulopalatopharyngoplasty(UPPP), and one case is in follow-up now. RESULT: Thyroxine replacement therapy was effective in improving symptoms and nocturnal sleep apnea. CONCLUSION: Hypothyroidism probably plays a significant role in the pathogenesis of obstructive sleep apnea, the satisfactory results would be obtained by thyroxine replacement therapy, CPAP or surgical treatment can be used as adjuvant therapy in patients with this disease.

Humans↗
PubMed2004

[The killing effect of cytotoxic T lymphocytes on esophageal adenocarcinoma cells mediated by gp96-peptide complexes].

OBJECTIVE: To study the immunotherapeutic effect on the esophageal adenocarcinoma mediated by gp96-peptide complexes isolated from the same kind of tumor. METHODS: gp96-peptide complexes were purified from nude mice tumors burdened by subcutaneous injection of human esophageal adenocarcinoma cell line SEG-1. gp96-peptide complexes were carried by the dendritic cells(DC) induced from human peripheral blood mononuclear cells to prepare gp96-DC vaccine. The proliferation of lymphocytes was tested with trypan-blue stain. The quantity of interferon-gamma(IFN-gamma) released from cytotoxic T lymphocytes (CTL) was detected with ELISA method. The killing effect of CTL on target cell SEG-1 was measured with MTT. RESULTS: We obtained 120 microg gp96 from 55 g tumor tissue. DC, gp96, and gp96-DC all could elicit the proliferation of lymphocytes and make them becoming into CTL which released IFN-gamma and showed different degrees of killing effect on target cell SEG-1. gp96-DC has the strongest eliciting effect among them. At the ratio of E(effect) to T(target) as 40:1,the killing rate was 68%. No significant difference between the effects of CTL induced by DC alone and of lymphocytes without specific antigen on SEG-1 and K562 cells. CONCLUSION: The gp96-peptide complexes from tumors can improve the effect of eliciting lymphocyte proliferation of DC and make the lymphocyte becoming into CTL more effectively. These CTLs show prominent killing effect on the target tumor cells.

Adenocarcinoma↗
PubMed2004

[The analysis of protracted inflammation after endoscopic surgery].

OBJECTIVE: To study the causes of late inflammation after endoscopic surgery. METHOD: Sixty-five patients of protracted inflammation after endoscopic surgery were investigated, by observing the pathologic spot and matched control of drug. RESULT: The orbit carton and aperture of frontal sinus and maxillary sinus were main spots of protracted inflammation. The drugs had no effect on protracted inflammation. CONCLUSION: The main cause of late inflammations is related to the high risk regions in endoscopic surgery.

Adult↗
PubMed2004

[Fluorescence spectra and fluorescence quantum yield of sulfosalicylic acid].

Fluorescence spectra and fluorescence quantum yield of sulfosalicylic acid (SSA) have been studied. Under the condition of pH<2, SSA has no fluorescence. With the increase in pH value, fluorescence intensity of SSA increases. In the range of pH 5-10.5, SSA gives a strong and steady fluorescence with a maximum emission wavelength at 402 nm and excitation wavelengths at 212, 238 and 297 nm, respectively. In strong alkaline solutions with pH>13, SSA exists as another fluorescence species with a maximum excitation wavelength at 261 nm and a maximum emission wavelength at 390 nm. The excitation spectrum of SSA changes when its concentration is relatively higher, but the emission spectrum remains unchanged. There is an excellent linear relationship between fluorescence intensity and the concentration of SSA under neutral condition. The linear range is 5-250 ng x mL(-1), and the detection limit is 5 ng x mL(-1). Using quinine bisulphate as a reference, fluorescence quantum yields of SSA at different wavelengths were measured. At the maximum excitation wavelength 297 nm, fluorescence quantum yield of SSA is 0.54.

Benzenesulfonates↗
PubMed2003

Approaches to mapping genetically correlated complex traits.

Our Markov chain Monte Carlo (MCMC) methods were used in linkage analyses of the Framingham Heart Study data using all available pedigrees. Our goal was to detect and map loci associated with covariate-adjusted traits log triglyceride (lnTG) and high-density lipoprotein cholesterol (HDL) using multipoint LOD score analysis, Bayesian oligogenic linkage analysis and identity-by-descent (IBD) scoring methods. Each method used all marker data for all markers on a chromosome. Bayesian linkage analysis detected a linkage signal on chromosome 7 for lnTG and HDL, corroborating previously published results. However, these results were not replicated in a classical linkage analysis of the data or by using IBD scoring methods.We conclude that Bayesian linkage analysis provides a powerful paradigm for mapping trait loci but interpretation of the Bayesian linkage signals is subjective. In the absence of a LOD score method accommodating genetically complex traits and linkage heterogeneity, validation of these signals remains elusive.

Cholesterol, HDL↗
PubMed2003

Prolonged effects of repeated cocaine on medial prefrontal cortex dopamine response to cocaine and a stressful predatory odor challenge in rats.

The present study examined the effects of seven daily saline (1 ml/kg, i.p.) or cocaine injections (15 mg/kg, i.p.) on extracellular dopamine levels in the medial prefrontal cortex (mPFC) after challenge with cocaine or stressful predatory odor presentation given 1 week (early withdrawal) or 3 weeks later (late withdrawal). Cocaine challenge at early withdrawal produced an increase in dopamine levels that was temporally shifted so that maximal levels of dopamine were significantly higher and attained 20 min earlier in the cocaine-pretreated group (maximal levels of saline controls=378% increase, cocaine=494% increase above baseline). Cocaine challenge at late withdrawal produced a similar effect on the temporal shift of maximal dopamine levels, with a significantly higher maximal percent increase of dopamine in cocaine-pretreated rats (saline-pretreated=420% increase, cocaine-pretreated=515% increase). Challenge with TMT, a predatory odor from fox that produces a stress response in rats, produced a maximal 75-200% increase in basal dopamine levels in both groups at both early and late withdrawal times. As with cocaine challenge, daily cocaine produced a leftward shift in the time at which maximal dopamine levels were attained in response to TMT. Cocaine-pretreated animals demonstrated maximal dopamine levels 40-80 min after TMT removal, while saline-pretreated rats showed maximal levels 100-140 min after TMT removal. These results suggest that there are long-term changes in the mPFC dopamine response to subsequent challenge with cocaine as well as a stressful predatory odor. The altered response of mPFC dopamine after repeated daily cocaine may impact relapse to drug-seeking or drug-taking behavior.

Animals↗
PubMed2003

3,3',5,5'-tetramethyl-N-(9-anthrylmethyl)benzidine: a dual-signaling fluorescent reagent for optical sensing of aliphatic aldehydes.

A new optical chemical sensor for continuous monitoring of aliphatic aldehydes has been proposed based on the reversible chemical reaction between a new sensing reagent, 3,3',5,5'-tetramethyl-N-(9-anthrylmethyl)benzidine (TMAB), and the analytes. TMAB, containing two receptors and two fluorescent reporters, can perform dual fluorescence responses corresponding to the reactions of hydrogen ion and carbonyl compound. When immobilized in a plasticized poly(vinyl chloride) membrane, TMAB extracts aliphatic aldehydes from aqueous solution into the bulk membrane phase and reacts with the analyte by forming a Schiff base. Since the extraction equilibrium and chemical reaction are accompanied by fluorescence increase of the sensing membrane, the chemical recognition process could be directly translated into an optical signal. At pH 3.20, the sensor exhibits a dynamic detection range from 0.017 to 4.2 mM n-butyraldehyde with a limit of detection of 0.003 mM. The forward response time (t95) of the sensor is 3-5 min, and the reverse response time is 5-7 min. The responses of the sensor toward different kinds of aldehydes and ketones depend on the lipophilicity and the reactivity of the analytes. Since the fluorescence enhancement of the sensing membrane at 296 nm/410 nm is only related to the formation of Schiff base, the measurement of aldehydes is independent of pH.

Journal Article↗
PubMed2003

HDAC-6 interacts with and deacetylates tubulin and microtubules in vivo.

Microtubules are cylindrical cytoskeletal structures found in almost all eukaryotic cell types which are involved in a great variety of cellular processes. Reversible acetylation on the epsilon-amino group of alpha-tubulin Lys40 marks stabilized microtubule structures and may contribute to regulating microtubule dynamics. Yet, the enzymes catalysing this acetylation/deacetylation have remained unidentified until recently. Here we report that beta-tubulin interacts with histone deacetylase-6 (HDAC-6) in a yeast two-hybrid assay and in vitro. We find that HDAC-6 is a micro tubule-associated protein capable of deacetylating alpha-tubulin in vivo and in vitro. HDAC-6's microtubule binding and deacetylation functions both depend on the hdac domains. Overexpression of HDAC-6 in mammalian cells leads to tubulin hypoacetylation. In contrast, inhibition of HDAC-6 function by two independent mechanisms--pharmacological (HDAC inhibitors) or genetic (targeted inactivation of HDAC-6 in embryonic stem cells)--leads to hyperacetylation of tubulin and microtubules. Taken together, our data provide evidence that HDAC-6 might act as a dual deacetylase for tubulin and histones, and suggest the possibility that acetylated non-histone proteins might represent novel targets for pharmacological therapy by HDAC inhibitors.

3T3 Cells↗
PubMed2003

Heat effect on the structure and activity of the recombinant glutamate dehydrogenase from a hyperthermophilic archaeon Pyrococcus horikoshii.

Glutamate dehydrogenase from Pyrococcus horikoshii (Pho-GDH) was cloned and overexpressed in Escherichia coli. The cloned enzyme with His-tag was purified to homogeneity by affinity chromatography and shown to be a hexamer enzyme of 290+/-8 kDa (subunit mass 48 kDa). Its optimal pH and temperature were 7.6 and 90 degrees C, respectively. The purified enzyme has outstanding thermostability (the half-life for thermal inactivation at 100 degrees C was 4 h). The enzyme shows strict specificity for 2-oxoglutarate and L-glutamate and requires NAD(P)H and NADP as cofactors but it does not reveal activity on NAD as cofactor. K(m) values of the recombinant enzyme are comparable for both substrates: 0.2 mM for L-glutamate and 0.53 mM for 2-oxoglutarate. The enzyme was activated by heating at 80 degrees C for 1 h, which was accompanied by the formation of its active conformation. Circular dichroism and fluorescence spectra show that the active conformation is heat-inducible and time-dependent.

Amino Acid Sequence↗