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Biomedical subjects

L Peng

Publications and source records attributed to L Peng.

At least 19 recordsLinked to original sources
PubMed2006

Overexpression of phosphatase of regenerating liver-3 in breast cancer: association with a poor clinical outcome.

BACKGROUND: Increasing evidence has suggested that phosphatase of regenerating liver-3 (PRL-3) plays an important role in cancer cell migration, invasion and metastasis. However, the correlation between the PRL-3 expression and clinical outcome in breast cancer has not been investigated. PATIENTS AND METHODS: Using a PRL-3-specific monoclonal antibody 3B6, PRL-3 expression was assessed by immunohistochemistry in tumor tissues from 382 breast cancer patients with a median follow-up of 65 months. RESULTS: We found that 34.8% patients expressed a high level of PRL-3 protein in their tumors. Patients with a high level of PRL-3 in the tumor had a worse disease-specific survival (DSS) rate than those with a low level of PRL-3 (74.0% versus 84.9%, P = 0.011), and PRL-3 remained an independent prognostic marker for DSS (HR 1.8, 95% CI 1.1-2.9, P = 0.019) in multivariate analysis. More importantly, in 219 node-negative patients, PRL-3 showed a significant correlation with DSS in univariate analysis (P = 0.014) and retained a borderline significance (HR 2.65, 95% CI 0.92-7.64, P = 0.071) in multivariate analysis. CONCLUSIONS: Our results suggest that PRL-3 may serve as an unfavorable prognostic marker in breast cancer, especially for patients with node-negative diseases. Thus, our findings may provide useful information for individualized therapy in the clinical setting.

Adult↗
PubMed2006

[Distribution of hepatitis B virus genotypes in Guizhou and analysis of clinical significance.].

BACKGROUND: To investigate the distribution of HBV genotypes in Guizhou and study the relationship between the genotype and the progression of liver disease. METHOD: Totally 693 patients with chronic HBV infection, from 4 areas of Guizhou, including 292 asymptomatic HBV carriers (ASC), 276 cases with chronic hepatitis (CH), 76 liver cirrhosis (LC), 49 hepatocellular carcinoma (HCC) were examined. The HBV genotype was determined by restriction fragment length polymorphism analysis and the relationship between HBV genotype and the progression of liver disease was studied by multifactor analysis such as HBsAg positivity, HBV DNA load and ALT level. RESULTS: Of the 693 patients, 6 (0.87%), 449 (64.79%), 233 (33.62%), and 5 (0.72%) belonged to genotype A, B, C and D, respectively. There was a statistically siganificant difference in the distribution of genotype B among Kaili (96.4%), Zunye (78.79%), Duyun (76.19%) and Guiyang (53.66%) areas (P less than 0.01). Genotype C was more prevalent in Guiyang than in other three areas (45.68% vs. 23.8%, 45.68% vs. 13.13%, 45.68% vs. 3.96%, P less than 0.01, respectively). There were also statistically significant difference in distribution of genotype B and C in various stages of liver disease (P less than 0.01). Genotype B showed a decreasing trend from ASC, CH, LC to HCC and genotype C was more frequent in patients with CH (45.92%) than in those with ASC (20.6%), LC (17.17%) and HCC (16.31%). The ALT levels and the mean ages were significantly higher and older in patients with genotype C than those in genotype B. The HBeAg positivity was significantly lower in genotype C than that in genotype B (48.07% vs 61.90%, P less than 0.01). CONCLUSION: Genotype A, B, C and D exist in Guizhou. Genotype B predominates and genotype C was the second common. The geographic distribution of genotype B and C are different in some areas of Guizhou. Compared with genotype B, genotype C is associated with the development of more severe liver damage.

China↗
PubMed2005

Heparin compromises streptokinase-induced arterial patency in rabbits.

INTRODUCTION: Little is known with regard to efficacy of heparin as an adjunct to fibrinolytics under conditions of severe vascular damage. In this study, we compared the effects of unfractionated heparin (UH), low-molecular weight heparin (LMWH), and recombinant desulfohirudin (HIR) in combination with streptokinase (SK) in such settings. MATERIALS AND METHODS: We used an established rabbit model, in which thrombosis, critical stenosis, and vascular wall damage were introduced to a segment of the abdominal aorta and the effects of the respective therapies were assessed by time to patency (TTP in minutes), cumulative patency (CP (%)), lysis of original clot (CL (%)), and net clot accretion (NCA (%)). Treatments were administered over 90 min at the following doses: SK: 33,000 U/kg, UH: 125-250 U/kg, LMWH: 1.25-2.5 mg/kg, HIR: 0.25-0.55 mg/kg. RESULTS: Unexpectedly, UH and LMWH had a paradoxical and detrimental effect on SK-mediated recanalization as measured by both TTP and CP. Thus, administration of SK vs. SK+UH or SK+LMWH resulted in TTP values of 43+/-8 min vs. 70+/-11 min (p<0.05) and 67+/-12 min. (p<0.08), respectively. For CP, the corresponding values were 21+/-7%, 0.5+/-0.3% and 9+/-8%. This delay in vessel recanalization occurred despite excessive systemic anticoagulation (activated partial thromboplastin time (aPTT) and thrombin clotting time (TCT) ratios >6 and >34, respectively). Of interest, both heparinoids completely inhibited SK-induced fibrinogen consumption (FC). In contrast, recombinant desulfohirudin (HIR) shortened SK-induced TTP (4.97+/-0.81 min) without preserving fibrinogen. CONCLUSIONS: Our findings suggest that caution needs to be exercised, when using the combination of SK and heparinoids for the treatment of arterial thrombosis under conditions of severe vascular damage and stenosis.

Animals↗
PubMed2005

Applications of topologically segregated bilayer beads in 'one-bead one-compound' combinatorial libraries.

We recently reported the use of a biphasic approach to generate topologically segregated bilayer beads. In generating 'one-bead one-compound' (OBOC) combinatorial libraries, novel encoding methods have been applied to these beads such as the testing library compound and the coding tags residing on the outer layer and inner core of each bead, respectively. In this report, we further exploit these bilayer beads by preparing target bead-libraries with low concentration of random peptides on the outer layer, and full substitution of coding peptides in the bead interior. The low concentration of peptide on the bead surface enables us to greatly increase the stringency of screening so that higher affinity ligands can easily be identified. Full substitution of the inner core of the beads enables us to have enough coding peptides inside the bead for direct microsequencing with Edman chemistry. The biphasic approach of preparing bilayer beads can be carried out at any point during the library construction. Therefore, the nonsequencable or fixed structures of the peptides can be bypassed in the coding tags. As a result, peptide libraries that otherwise cannot be sequenced can now be sequenced, and peptide segments with fixed residues within the libraries can be bypassed so that the microsequencing time can be significantly shortened. Furthermore, peptides with a branch of random sequence in the middle of a fixed peptide chain can be encoded with just the random sequence in the bead interior. We have successfully applied these novel OBOC library concepts in the optimization of cell-surface ligands for a human T-cell leukemia, Jurkat, cell line.

Alkaline Phosphatase↗
PubMed2004

Time-dependent speckle in holographic optical coherence imaging and the health of tumor tissue.

Holographic optical coherence imaging acquires en face images from successive depths inside scattering tissue. In a study of multicellular tumor spheroids the holographic features recorded from a fixed depth are observed to be time dependent, and they may be classified as variable or persistent. The ratio of variable to persistent features, as well as speckle correlation times, provides quantitative measures of the health of the tissue. Studies of rat osteogenic sarcoma tumor spheroids that have been subjected to metabolic and cross-polymerizing poisons provide quantitative differentiation among healthy, necrotic, and poisoned tissue. Organelle motility in healthy tissue appears as super-Brownian laser speckle, whereas chemically fixed tissue exhibits static speckle.

Animals↗
PubMed2004

T-helper and T-cytotoxic cell subsets monitoring during active cytomegalovirus infection in liver transplantation.

OBJECTIVE: The objectives of this study was to analyze the peripheral blood T-lymphocyte subsets of the Th1-related versus Th2-related cytokines of CD4+ cells, and the Tc1 versus Tc2 cytokines of CD8+ cells liver transplant recipients with versus without active cytomegalovirus (CMV) infection. METHODS: Isolated peripheral blood mononuclear cells (PBMC) were stimulated using PMA/Ionomycin/Monensin. Interleukin (IL)-4 and interferon gamma (IFN-gamma) production by CD4+ and CD8+T cells were determined using fluorescence-activated cell sorter (FACS) analysis. RESULTS: The ratios of CD4/CD8 were significantly lower among active CMV-infected patients. The levels of Th2 and Tc2 cytokines (IL-4) were similar between CMV-infected and uninfected patients. However, the levels of Th1-type and Tc1-type cytokines (IFN-r) were significantly lower among active CMV-infected patients. CONCLUSIONS: Low levels of Th1-type cytokines seem to correlate with active CMV infection in liver transplant recipients.

Antigens, CD↗
PubMed2004

Astrocytic adrenoceptors: a major drug target in neurological and psychiatric disorders?

Considerable attention has recently been paid to astrocyte functions, which are briefly summarized. A large amount of data is available about adrenoceptor expression and function in astrocytes, some of it dating back to the 1970's and some of it very recent. This material is reviewed in the present paper. The brain is innervated by noradrenergic fibers extending from locus coeruleus in the brain stem, which in turn is connected to a network of adrenergic and noradrenergic nuclei in the medulla and pons, contributing to the control of (nor)adrenergic, serotonergic, dopaminergic and cholinergic function, both in the central nervous system (CNS) and in the periphery. In the CNS astrocytes constitute a major target for noradrenergic innervation, which regulates morphological plasticity, energy metabolism, membrane transport, gap junction permeability and immunological responses in these cells. Noradrenergic effects on astrocytes are essential during consolidation of episodic, long-term memory, which is reinforced by beta-adrenergic activation. Glycogenolysis and synthesis of glutamate and glutamine from glucose, both of which are metabolic processes restricted to astrocytes, occur at several time-specific stages during the consolidation. Astrocytic abnormalities are almost certainly important in the pathogenesis of multiple sclerosis and in all probability contribute essentially to inflammation and malfunction in Alzheimer's disease and to mood disturbances in affective disorders. Noradrenergic function in astrocytes is severely disturbed by chronic exposure to cocaine, which also changes astrocyte morphology. Development of drugs modifying noradrenergic receptor activity and/or down-stream signaling is advocated for treatment of several neurological/psychiatric disorders and for neuroprotection. Astrocytic preparations are suggested for study of mechanism(s) of action of antidepressant drugs and pathophysiology of mood disorders.

Adrenergic Agents↗
PubMed2003

Ultrasound detection through turbid media.

Optical coherence-domain reflectometry and laser-based ultrasound detection have been combined with the use of adaptive optics to detect ultrasound through turbid media. The dynamic hologram in a photorefractive quantum-well device performs as a coherence gate that eliminates multiply scattered background. Quadrature homodyne detection conditions are selected by the choice of center wavelength of the pulse spectrum, requiring no active stabilization or feedback. A depth resolution of 30 microm was achieved, with a pulse duration of nominally 120 fs for ultrasound detection through turbid media up to optical thicknesses of 11 mean free scattering lengths.

Holography↗
PubMed2003

High-speed adaptive interferometer for optical coherence-domain reflectometry through turbid media.

Two-wave mixing in a dynamic holographic film acts as the adaptive beam combiner in a short-coherence interferometer that performs optical coherence-domain reflectometry (OCDR) through turbid media. This approach combines the high spatial resolution and sensitivity of coherence-domain reflectometry with photorefractive quantum-well-based adaptive homodyne detection. A depth resolution of 28 microm and penetration through 16 mean free paths in a turbid medium have been obtained in this adaptive OCDR application.

Interferometry↗
PubMed2003

Global metabolic regulation analysis for Escherichia coli K12 based on protein expression by 2-dimensional electrophoresis and enzyme activity measurement.

Regulation of the main metabolic pathways of Escherichia coli K12 was investigated based on 2-dimensional electrophoresis (2DE) and the measurement of enzyme activities. The cells were grown aerobically in different carbon sources, such as glucose, acetate, gluconate or glycerol. Microaerobic cultivation was also conducted with glucose as a carbon source. Fifty-two proteins could be identified based on 2DE, and 26 enzyme activities from the main metabolic pathways-including glycolysis, pentose phosphate pathway, TCA cycle, Entner-Doudoroff pathway and fermentative pathway-were assayed. These enzyme activities, together with global and quantitative protein expression, gave us a clear picture of metabolic regulation. The results show that, compared with the control experiment with glucose as a carbon source under aerobic conditions, glycolytic enzymes were slightly up-regulated (<2-fold), TCA cycle enzymes were significantly down-regulated (2- to 10-fold), and fermentative enzymes such as pfl and adhE were highly up-regulated (>10-fold) under microaerobic conditions in glucose medium. When acetate was used as a carbon source, pfkA, pykF, ppc and zwf were down-regulated, while fbp, pckA, ppsA and mez were significantly up-regulated. Glyoxylate enzymes such as aceA and aceB were strongly up-regulated (>10-fold) and TCA-cycle-related enzymes were also up-regulated to some extent. With gluconate as a carbon source, edd, eda, fbp and TCA cycle enzymes were up-regulated. With glycerol as a carbon source, fbp and TCA cycle enzymes were up-regulated, while ackA was significantly down-regulated. Protein abundance obtained by 2DE correlated well with enzyme activity, with a few exceptions (e.g., isocitrate dehydrogenase), during aerobic growth on acetate.

Electrophoresis, Gel, Two-Dimensional↗
PubMed2003

Influence of Th1, Th2, and Th3 cytokines during the early phase after liver transplantation.

To investigate the change of Th1, Th2, Th3 cytokines during early liver transplantation. IFN-r, IL-4, TGF-beta production by CD4+ T cells were determined by fluorescence activated cell sorter analysis. Comparing the acute rejection with the non-acute rejection groups on the 7th, 14th, and 28th day showed that high interferon-gamma production associated with acute rejection in the early posttransplant period. There was no evidence of significant changes in interleukin-4 and transforming growth factor beta (TGF-beta) levels between non-acute rejection groups with acute rejection groups. Th1 cytokine high production is significantly associated with acute rejection in liver transplant recipients.

CD4-CD8 Ratio↗
PubMed2001

Augmentation versus inhibition: effects of conjunctional OX-40 receptor monoclonal antibody and IL-2 treatment on adoptive immunotherapy of advanced tumor.

Therapeutic efficacy of adoptive immunotherapy of malignancies is proportional to the number of effector T cells transferred. Traditionally, exogenous IL-2 treatment has been used to promote the survival and function of transferred cells. Recently, we described the therapeutic effects of in vivo ligation of the costimulatory receptor, OX-40R, on activated T cells during early tumor growth. In this study, we examined the effects of IL-2 and OX-40R mAb on adoptive immunotherapy of advanced tumors. For treatment of 10-day 3-methylcholanthrene 205 pulmonary metastases, systemic transfer of 50 x 10(6) activated tumor-draining lymph node T cells resulted in >99% reduction of metastatic nodules. With either IL-2 or OX-40R mAb conjunctional treatment, only 20 x 10(6) cells were required. Advanced 10-day 3-methylcholanthrene 205 intracranial tumors could be cured by the transfer of 15 x 10(6) L-selectin(low) T cells derived from draining lymph nodes. In this situation, IL-2 administration inhibited therapeutic effects of the transferred cells. By contrast, 5 x 10(6) T cells were sufficient to cure all mice if OX-40R mAb was administrated. Studies on trafficking of systemically transferred T cells revealed that IL-2, but not OX-40R mAb, impeded tumor infiltration by T cells. Tumor regression required participation of both CD4 and CD8 T cells. Because only CD4 T cells expressed OX-40R at cell transfer, direct CD4 T cell activation is possible. Alternatively, OX-40R might be up-regulated on transferred T cells at the tumor site, rendering them reactive to the mAb. Our study suggests OX-40R mAb to be a reagent of choice to augment T cell adoptive immunotherapy in clinical trials.

Adjuvants, Immunologic↗
PubMed2001

Dynamic deconvolution of a pre-equilibrated dynamic combinatorial library of acetylcholinesterase inhibitors.

A dynamic combinatorial library composed of interconverting acylhydrazones has been generated and screened towards inhibition of acetylcholinesterase from the electric ray Torpedo marmorata. Starting from a small set (13) of initial hydrazide and aldehyde building blocks, a library containing possibly 66 different species was obtained in a single operation. Of all possible acylhydrazones formed, active compounds containing two terminal cationic recognition groups separated by an appropriate distance, permitting two-site binding, could be rapidly identified by using a dynamic deconvolution--screening procedure, based on the sequential removal of starting building blocks. A very potent bis-pyridinium inhibitor (K(i)=1.09 nM, alphaK(i)=2.80 nM) was selected from the process and the contribution of various structural features to inhibitory potency was evaluated.

Acetylcholinesterase↗
PubMed2001

Tissue-specific and ubiquitous promoters direct the expression of alternatively spliced transcripts from the calcitonin receptor gene.

The gene encoding the murine calcitonin receptor (mCTR) was isolated, and the exon/intron structure was determined. Analysis of transcripts revealed novel cDNA sequences, new alternative exon splicing in the 5'-untranslated region, and three putative promoters (P1, P2, and P3). The longest transcription unit is greater than 67 kilobase pairs, and the location of introns within the coding region of the mCTR gene (exons E3-E14) are identical to those of the porcine and human CTR genes. We have identified novel cDNA sequences that form three new exons as well as others that add 512 base pairs to the 5' side of the previously published cDNA, thereby extending exon E1 to 682 base pairs. Two of these novel exons are upstream of exon E2 and form a tripartite exon E2 (E2a, E2b, and E2c) in which E2a is utilized by promoter P2 with variable splicing of E2b. The third new exon (E3b') lies between E3a and E3b and is utilized by promoter P3. Analysis of mCTR mRNAs has revealed that the three alternative promoters give rise to at least seven mCTR isoforms in the 5' region of the gene and generate 5'-untranslated regions of very different lengths. Analysis by reverse transcription-polymerase chain reaction shows that promoters P1 and P2 are utilized in osteoclasts, brain, and kidney, whereas promoter P3 appears to be osteoclast-specific. Using transiently transfected reporter constructs, promoter P2 has activity in both a murine kidney cell line (MDCT209) and a chicken osteoclast-like cell line (HD-11EM), whereas promoter P3 is active only in the osteoclast-like cell line. These transfection data confirm the osteoclast specificity of promoter P3 and provide the first evidence that the CTR gene is regulated in a tissue-specific manner by alternative promoter utilization.

Alternative Splicing↗
PubMed2001

Nicotine and amyloid formation.

The major protein constituents of amyloid deposits in Alzheimer's disease (AD) are the 40-residue beta-amyloid (Abeta) (1-40) peptide and the 42-residue Abeta(1-42) peptide. The Abeta(1-42) is more pathogenic and produced in greater quantities in familial forms of AD. A major goal of research is to uncover a suitable inhibitor that either slows down or inhibits Abeta formation (beta-amyloidosis). During beta-amyloidosis, structural changes associated with the conversion of monomeric Abeta peptide building blocks into the aggregated fibrillar beta-sheet structures occur (alpha-helix-->beta-sheet or random, extended chain-->beta-sheet). In previous work, we and others established that nicotine, a major component of cigarette smoke, inhibits beta-amyloidosis of the Abeta(1-42), which may result from nicotine binding to the alpha-helical structure. These conclusions were based on solution nuclear magnetic resonance (NMR) spectroscopic studies with the nonnative 28-residue Abeta(1-28). This information suggests that, when administered therapeutically to AD patients, nicotine may not only affect cholinergic activation, but could also conceivably alter amyloid deposition. In this report, NMR studies were augmented with the naturally occurring Abeta(1-42), under conditions where the peptide folds into a predominantly alpha-helical or random, extended chain structure. The major result is that nicotine shows only modest binding to these conformations, indicating that the nicotine inhibition to beta-amyloidosis probably results from binding to a small, soluble beta-sheet aggregate that is NMR invisible.

Alzheimer Disease↗
PubMed2001

Effects of L-glutamate, D-aspartate, and monensin on glycolytic and oxidative glucose metabolism in mouse astrocyte cultures: further evidence that glutamate uptake is metabolically driven by oxidative metabolism.

The hypothesis was tested that oxidative metabolism, mainly fueled by glutamate itself, provides the energy for active, Na(+),K(+)-ATPase-catalyzed Na(+) extrusion following glutamate uptake in conjunction with Na(+). This hypothesis was supported by the following observations: (i) glutamate had either no effect or caused a slight reduction in glycolytic rate, measured as deoxyglucose phosphorylation; (ii) D-aspartate, which is accumulated by the L-glutamate carrier, but cannot be metabolized by the cells, caused an increase in glycolytic rate; (iii) monensin which, like D-aspartate, stimulates the intracellular, Na(+)-activated site of the Na, K-ATPase and thus energy metabolism, but provides no metabolic substrate, stimulated both glycolysis and glucose oxidation; and (iv) oxidation of glucose was potently inhibited by glutamate, although glutamate is known to stimulate oxygen consumption in primary cultures of astrocytes, a combination showing that oxidation of a non-glucose substrate is increased in the presence of glutamate. These findings should be considered in attempts to understand metabolic interactions between neurons and astrocytes and regulation of energy metabolism in brain.

Animals↗