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Biomedical subjects

L Zhang

Publications and source records attributed to L Zhang.

At least 433 records · Page 24Linked to original sources
PubMed2001

cDNA transfection of amino-terminal fragment of urokinase efficiently inhibits cancer cell invasion and metastasis.

Focusing of urokinase-type plasminogen activator (uPA) to the cell surface via binding to its specific receptor (uPAR, CD87) is critical for tumor invasion and metastasis. Consequently, the inhibition of uPA-uPAR interaction on the cell surface might be a promising anti-invasion and anti-metastasis strategy. We examined the effects of cDNA transfection of the human uPA amino-terminal fragment (ATF) on invasion and metastasis of cancer cells. First, a highly metastatic human lung giant-cell carcinoma cell line (PG), used as the target cell for evaluation of this effect, was demonstrated to express both uPA and uPAR. Then, ATF, which contains an intact uPAR binding site but is catalytically inactive, was designed as an antagonist of uPA-uPAR interaction and was transfected into PG cells. [(3)H]-Thymidine incorporation and cell growth curves indicated that expressed ATF did not affect the proliferation of transfected cells. However, analysis by scanning electron microscopy revealed that ATF changed the host cells from the typical invasive phenotype to a noninvasive one. Correspondingly, the modified Boyden chamber test in vitro showed that ATF expression significantly decreased the invasive capacity of transfected cells. Furthermore, in the spontaneous metastasis model, it was confirmed in vivo that expressed ATF remarkably inhibited lung metastasis of implanted ATF-transfected PG cells. In summary, autocrine ATF could act as an antagonist of uPA-uPAR interaction, and ATF cDNA transfection could efficiently inhibit the invasion and metastasis of the cancer cells. Inhibition of uPA-uPAR interaction on the cell surface might be a promising anti-invasion and anti-metastasis strategy.

Animals↗
PubMed2001

Perfect phylogenetic networks with recombination.

The perfect phylogeny problem is a classical problem in evolutionary tree construction. In this paper, we propose a new model called phylogenetic network with recombination that takes recombination events into account. We show that the problem of finding a perfect phylogenetic network with the minimum number of recombination events is NP-hard; we also present an efficient polynomial time algorithm for an interesting restricted version of the problem.

Algorithms↗
PubMed2001

Soluble Fas (CD95) is a prognostic factor in patients with metastatic breast cancer undergoing high-dose chemotherapy and autologous stem cell transplantation.

The Fas/Fas ligand (FasL) system plays an important role in cellular apoptosis and is involved in cancer cell death induced by the immune system and anticancer drugs. Increased serum levels of soluble Fas (sFas) are associated with a number of different disease states and with tumor progression and metastasis in patients. In this study, we examined the plasma levels of sFas in 94 women with metastatic breast cancer undergoing high-dose chemotherapy (HDCT) treatment with autologous stem cell transplantation (ASCT) using a quantitative enzyme-linked immunosorbent assay (ELISA) method. Thirty-one patients (31/94, 33%) had plasma sFas levels greater than the optimum cut point of 1.90 ng/ml (median 2.47, range 1.98-13.54 ng/ml) and were designated as sFas positive. Sixty-three patients (63/94, 67%) had sFas levels below 1.90 ng/ml (median 1.14, range 0.47-1.89 ng/ml). In univariate analysis, patients with sFas-positive status, HER-2 overexpression, and the presence of liver metastases had a significantly shorter time to disease progression (PFS) and significantly decreased overall survival (OS). Multivariable analysis (Cox proportional hazards model) for PFS determined that sFas status significantly predicted disease progression (p = 0.004) with an adjusted hazard ratio (HR) of 2.0 (95% CI, 1.3-3.3). HER-2 status and liver metastases were also significant independent predictors of disease progression (p < 0.001) for both. sFas level was also an independent prognostic factor for OS with an adjusted HR of 2.0 (p = 0.006; 95% CI, 1.2-3.4). HER-2 status and liver metastases also remained highly significant independent prognostic factors for OS (HER-2: p < 0.001, HR 2.3, and liver metastases: p = 0.001, HR 2.7). In conclusion, these results suggest that plasma levels of sFas may be a valuable clinical prognostic factor in predicting outcome (PFS and OS) for patients with metastatic breast cancer undergoing HDCT with ASCT.

Adult↗
PubMed2001

Fluoroquinolone susceptibilities of efflux-mediated multidrug-resistant Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Burkholderia cepacia.

The antibacterial activities of seven fluoroquinolones (ciprofloxacin, BAYy3118, clinafloxacin, gemifloxacin, moxifloxacin, sparfloxacin and trovafloxacin) against isogenic efflux-mediated multidrug-resistant strains of Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Burkholderia cepacia, were compared. The results indicate that these fluoroquinolones are all substrates for the multidrug efflux systems of these organisms. Clinafloxacin was found generally to be the most active agent against multidrug-resistant strains.

Anti-Infective Agents↗
PubMed2001

Intracellular localization and movement phenotypes of alfalfa mosaic virus movement protein mutants.

Thirteen mutations were introduced in the movement protein (MP) gene of Alfalfa mosaic virus (AMV) fused to the green fluorescent protein (GFP) gene and the mutant MP-GFP fusions were expressed transiently in tobacco protoplasts, tobacco suspension cells, and epidermal cells of tobacco leaves. In addition, the mutations were introduced in the MP gene of AMV RNA 3 and the mutant RNAs were used to infect tobacco plants. Ten mutants were affected in one or more of the following functions of MP: the formation of tubular structures on the surface of protoplasts, association with the endoplasmic reticulum (ER) of suspension cells and epidermal cells, targeting to punctate structures in the cell wall of epidermis cells, movement from transfected cells to adjacent cells in epidermis tissue, cell-to-cell movement, or long-distance movement in plants. The mutations point to functional domains of the MP and support the proposed order of events in AMV transport. Studies with several inhibitors indicate that actin or microtubule components of the cytoskeleton are not involved in tubule formation by AMV MP. Evidence was obtained that tubular structures on the surface of transfected protoplasts contain ER- or plasmalemma-derived material.

Alfalfa mosaic virus↗
PubMed2001

Extracellular matrix protein 1 (ECM1) has angiogenic properties and is expressed by breast tumor cells.

Tumor growth and metastasis are critically dependent on the formation of new blood vessels. The present study found that extracellular matrix protein 1 (ECM1), a newly described secretory glycoprotein, promotes angiogenesis. This was initially suggested by in situ hybridization studies of mouse embryos indicating that the ECM1 message was associated with blood vessels and its expression pattern was similar to that of flk-1, a recognized marker for endothelium. More direct evidence for the role of ECM1 in angiogenesis was provided by the fact that highly purified recombinant ECM1 stimulated the proliferation of cultured endothelial cells and promoted blood vessel formation in the chorioallantoic membrane of chicken embryos. Immunohistochemical staining with specific antibodies indicated that ECM1 was expressed by the human breast cancer cell lines MDA-435 and LCC15, both of which are highly tumorigenic. In addition, staining of tissue sections from patients with breast cancer revealed that ECM1 was present in a significant proportion of primary and secondary tumors. Collectively, the results of this study suggest that ECM1 possesses angiogenic properties that may promote tumor progression.

Angiogenesis Inducing Agents↗
PubMed2001

Keratinocyte growth factors radioprotect bowel and bone marrow but not KHT sarcoma.

Various members of the fibroblast growth factor (FGF) family of proteins have been shown to protect against acute and late radiation damage of normal tissues. Protection of the small bowel, for example, occurs via both increased proliferation and reduced apoptosis. Other beneficial effects of FGFs include promotion of bone growth, pneumonitis prevention, and apoptosis suppression of endothelium in vivo and in vitro after irradiation. This protection against radiation requires only low and infrequent doses of FGFs. Two newly identified members of the FGF family, FGF7 and FGF10, have effects similar to many of the other FGF family proteins, but with more specificity for normal epithelial structures. For this reason, they have also been named keratinocyte growth factors one and two (KGF1 and KGF2, respectively). We therefore examined the potential utility of KGFs for radioprotection of the bone marrow and small bowel and examined safety issues concerning their adverse effects on KHT sarcoma. The results suggest that KGFs could be safely used to prevent radiation toxicity of the abdomen or pelvis and may in fact improve tumor response to radiation.

Animals↗
PubMed2001

Virtual reality in the assessment of selected cognitive function after brain injury.

OBJECTIVE: To assess selected cognitive functions of persons with traumatic brain injury using a computer-simulated virtual reality environment. STUDY DESIGN: A computer-simulated virtual kitchen was used to assess the ability of 30 patients with brain injury and 30 volunteers without brain injury to process and sequence information. The overall assessment score was based on the number of correct responses and the time needed to complete daily living tasks. Identical daily living tasks were tested and scored in participants with and without brain injury. Each subject was evaluated twice within 7 to 10 days. A total of 30 tasks were categorized as follows: information processing, problem solving, logical sequencing, and speed of responding. RESULTS: Persons with brain injuries consistently demonstrated a significant decrease in the ability to process information (P = 0.04-0.01), identify logical sequencing (P = 0.04-0.01), and complete the overall assessment (P < 0.01), compared with volunteers without brain injury. The time needed to process tasks, representing speed of cognitive responding, was also significantly different between the two groups (P < 0.01). CONCLUSION: A computer-generated virtual reality environment represents a reproducible tool to assess selected cognitive functions and can be used as a supplement to traditional rehabilitation assessment in persons with acquired brain injury.

Activities of Daily Living↗
PubMed2001

Evaluation of CT time-density curves of lower-limb veins.

UNLABELLED: Szapiro D, Ghaye B, Willems V, et al. Evaluation of CT time-density curves of lower-limb veins. Invest Radiol 2001;36:164-169. RATIONALE AND OBJECTIVES: To evaluate time-density curves of the lower-limb veins for optimization of CT venography. METHODS: Fifty patients referred for chest CT were randomized into five equal groups. Five anatomic levels (abdomen, pelvis, proximal thigh, knee, and midcalf) were evaluated by a dynamic acquisition during 7 minutes. Computed tomography attenuation values of the veins, arteries, and adjacent muscles were measured for each level and plotted into curves versus time. Venous enhancement was also assessed qualitatively. RESULTS: Mean peak enhancement values of the inferior vena cava and the iliac, femoral, popliteal, anterior tibial, posterior tibial, and peroneal veins were, respectively, 112 +/- 16, 103 +/- 17, 93 +/- 23, 98 +/- 30, 112 +/- 28, 137 +/- 28, and 124 +/- 29 Hounsfield units. These were reached at 93 +/- 9.5, 129 +/- 15, 135 +/- 20, 147 +/- 57, 124 +/- 32, 123 +/- 17, and 123 +/- 18 seconds. Homogeneous opacification was obtained after 210 seconds. An optimal time window for CT venography was obtained between 210 and 240 seconds for the calf level and between 180 and 300 seconds for above-knee veins. CONCLUSIONS: For sequential CT venography, a caudocranial acquisition of the lower-limb veins, starting at 210 seconds, should allow optimal clot detection.

Adult↗
PubMed2001

Up-regulation of neuropilin-1 in neovasculature after focal cerebral ischemia in the adult rat.

During development, neuropilin-1 is a receptor for semaphorin 3a-mediated axonal guidance and for vascular endothelial growth factor (VEGF) promotion of angiogenesis. The authors measured neuropilin-1 expression in the adult ischemic brain using Northern blot, in situ hybridization, and immunohistochemistry. Neuropilin-1 mRNA was significantly up-regulated as early as 2 hours and persisted at least 28 days after focal cerebral ischemia. Acute up-regulation of neuropilin-1 mRNA primarily localized to the ischemic neurons. A marked increase in both mRNA and protein of neuropilin-1 was detected in endothelial cells of cerebral blood vessels at the border and in the core of the ischemic lesion 7 days after ischemia, and neuropilin-1 gene expression persisted on these vessels for at least 28 days after ischemia. In these areas, neovascularization was detected using three-dimensional reconstructed images obtained from laser scanning confocal microscopy. Activated astrocytes also exhibited neuropilin-1 immunoreactivity during 7 to 28 days of ischemia. Double immunofluorescent staining showed colocalization of neuropilin-1 and VEGF to cerebral blood vessels and activated astrocytes. These data suggest that in addition to its role in axonal growth, up-regulation of neuropilin-1, in concert with VEGF and its receptors, may contribute to neovascular formation in the adult ischemic brain.

Animals↗
PubMed2001

L-Arginine improves endothelial function in renal artery of hypertensive Dahl rats.

OBJECTIVES: To clarify whether endothelium-derived contracting factor (EDCF) is developed in renal artery of hypertensive Dahl rats and whether prolonged oral L-arginine treatments prevent development of EDCF and hypertension. DESIGN: The effect of prolonged salt treatment with or without L-arginine on the renal artery was examined. METHODS AND RESULTS: Dahl salt-sensitive and -resistant rats were fed a 0.4 or an 8% NaCl diet for 4 weeks. High sodium intake increased arterial pressure in Dahl salt-sensitive rats. The rings of renal arteries were suspended for isometric tension recording. Only in the hypertensive rats, more than 1 micromol/l acetylcholine induced an endothelium-dependent contraction response. The contraction was completely inhibited by indomethacin or ONO-3708 [prostaglandin H2 (PGH2)/thromboxane A2 (TXA2) receptor antagonist], and partially inhibited by OKY-046 (TXA2 synthetase inhibitor). Acetylcholine-induced relaxation was significantly depressed in hypertensive rats, which was partially improved by SQ29548 (PGH2/TXA2 receptor antagonist). Oral L-arginine, but not ONO-8809 (orally active PGH2/TXA2 receptor antagonist) treatment, inhibited the contraction and amended the relaxation. The endothelium-independent contraction to TXA2 receptor agonist U46619 and relaxation to nitroprusside were not altered by L-arginine treatment The L-Arginine treatment reduced blood pressure and sodium retention with increases in urinary NO2-/NO3- and cGMP excretion. Hydralazine treatment also inhibited development of EDCF. CONCLUSIONS: The present results suggest that impaired endothelium-dependent relaxation to acetylcholine is caused in part by induction of EDCF synthesis/release in renal arteries of hypertensive Dahl rats. L-arginine can attenuate sodium retention and development of hypertension, which lead to a decrease in EDCF synthesis in renal arteries.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2001

Angiotensin converting enzyme inhibitor restrains inflammation-induced vascular injury in mice.

OBJECTIVES: Recent advances in molecular genetics made the mouse model important for studying the genetic basis of hypertension and vascular diseases such as the components of the renin-angiotensin system. This study was undertaken to investigate the role of angiotensin converting enzyme (ACE) in the mouse vascular injury model. DESIGN AND METHODS: Inflammation-induced vascular injury was created by placing a polyethylene cuff around the femoral artery of 12-14-week-old male FVB/N mice. Cuffed arteries were harvested and applied to reverse transcriptase-polymerase chain reaction analysis and immunohistochemistry for ACE. Subsequently, the effects of an ACE inhibitor, perindopril (3 mg/kg per day), on neointimal thickening were examined 2 weeks after cuff placement The influence of a nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 20 mg/kg per day) on the effects of perindopril was also examined. RESULTS: ACE mRNA expression increased in a time-dependent manner up to 2 weeks after cuff placement. Immunoreactive ACE was localized in the endothelium in the intact artery, while positive staining was observed in the medial and neointimal layer as well as in the periadventitial region of the cuffed artery. The intimamedia area ratio was significantly decreased by perindopril treatment (vehicle, 0.75+/-0.10; perindopril, 0.32+/-0.04; P< 0.05). The effect of perindopril was abrogated by coadministration of L-NAME whereas L-NAME alone did not affect the intima-media ratio (L-NAME, 0.66+/-0.11; perindopril + L-NAME, 0.72+/-0.09). CONCLUSIONS: This study provides evidence that ACE plays a role in cuff-induced neointimal thickening in mice. Nitric oxide may contribute, at least in part, to the inhibitory effects of perindopril.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

Maternal cocaine administration during pregnancy induces apoptosis in fetal rat heart.

We have previously demonstrated that cocaine induces apoptosis in primary cultures of fetal rat cardiomyocytes. The current study was designed to determine whether cocaine administered to the mother during pregnancy induced apoptosis in fetal rat heart. Pregnant rats were treated with cocaine subcutaneously (30 and 60 mg/kg per day) starting at day 15 of gestation and were terminated at day 21. Cocaine produced a dose-dependent increase in apoptotic cell death in the fetal heart by 1.3-fold (30 mg/kg per day) and 2.4-fold (60 mg/kg per day) of the control level (1.99+/-0.15%). Cocaine-induced DNA fragmentation in the fetal heart showed characteristic apoptotic ladder. In accordance, cocaine dose-dependently increased activities of caspase-3, caspase-8, and caspase-9 in the fetal heart by 0.5-, 0.6-, and 0.6-fold, respectively, at 30 mg/kg per day, and by 3.3-, 2.9-, and 2.3-fold, respectively, at 60 mg/kg per day. In contrast, cocaine showed no effect on caspase activities in the maternal heart. Bcl-2 and Bax proteins were detected in fetal rat heart, with 2.2-fold higher expression of Bcl-2 than Bax. Cocaine significantly increased Bax protein levels and decreased Bcl-2 protein levels, leading to a 7.5-fold increase in the Bax-to-Bcl-2 ratio in fetal rat heart. We conclude that cocaine causes apoptosis in fetal rat heart in vivo by upregulating the Bax-to-Bcl-2 ratio and increasing caspase activities, which is likely to play an important role in the adverse effects of cocaine on heart development.

Animals↗
PubMed2001

Differentiating between progressive supranuclear palsy and corticobasal degeneration by brain perfusion SPET.

The purpose of this study was to evaluate the usefulness of brain perfusion single photon emission computed tomography (SPET) to differentiate between progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Twelve patients with PSP and 12 with CBD were examined by brain perfusion SPET using 99Tc(m)-ethyl cysteinate dimer (99Tc(m)-ECD). The regions of interest (ROIs) were five cortical regions, the basal ganglia, the thalamus, the cerebellar cortex and the brain stem. The mean regional cerebral blood flow (CBF) and the mean right/left asymmetry index in each ROI were calculated. The asymmetry index of the regional CBF was significantly higher in CBD patients compared with PSP patients in all of the cortical regions and in the basal ganglia. The greatest differences in asymmetry were in the parietal cortex (P<0.001), high frontal cortex (P<0.001), frontal cortex (P<0.005), temporal cortex (P<0.01) and basal ganglia (P<0.01). Significant asymmetry was also detected in the occipital cortex (P < 0.05). No significant difference in asymmetry was found in the thalamus or the cerebellum. There were no significant differences between the two groups in any of the regional CBF values. In conclusion, brain perfusion SPET with 99Tc(m)-ECD is useful in detecting the significantly higher perfusion asymmetry in CBD patients compared with PSP patients in all cortical regions and in the basal ganglia. SPET may be a useful tool for differentiating between PSP and CBD.

Aged↗
PubMed2001

An intervention trial to inhibit the progression of precancerous gastric lesions: compliance, serum micronutrients and S-allyl cysteine levels, and toxicity.

Gastric cancer is the second most frequent cause of death from cancer in the world and the leading cause of death from cancer in China. In September 1995, we launched a randomized multi-intervention trial to inhibit the progression of precancerous gastric lesions in Linqu County, Shandong Province, an area of China with one of the world's highest rates of gastric cancer. Treatment compliance was measured by pill counts and quarterly serum concentrations of vitamin C, vitamin E and S-allyl cysteine. In 1999, toxicity information was collected from each trial participant to evaluate treatment-related side-effects during the trial. Compliance rates were 93% and 92.9% for 39 months of treatment with the vitamins/mineral and garlic preparation, respectively. The means for serum concentrations of vitamins C and E were 7.2 microg/ml and 1695 microg/dl among subjects in the active treatment groups compared with 3.1 microg/ml and 752 microg/dl among subjects in the placebo treatment group, respectively. No significant differences in side-effects were observed between the placebo treatment group and the vitamins/mineral and garlic preparation treatment groups during the 39-month trial period.

Adult↗
PubMed2001

Hydrogen peroxide is involved in abscisic acid-induced stomatal closure in Vicia faba.

One of the most important functions of the plant hormone abscisic acid (ABA) is to induce stomatal closure by reducing the turgor of guard cells under water deficit. Under environmental stresses, hydrogen peroxide (H(2)O(2)), an active oxygen species, is widely generated in many biological systems. Here, using an epidermal strip bioassay and laser-scanning confocal microscopy, we provide evidence that H(2)O(2) may function as an intermediate in ABA signaling in Vicia faba guard cells. H(2)O(2) inhibited induced closure of stomata, and this effect was reversed by ascorbic acid at concentrations lower than 10(-5) M. Further, ABA-induced stomatal closure also was abolished partly by addition of exogenous catalase (CAT) and diphenylene iodonium (DPI), which are an H(2)O(2) scavenger and an NADPH oxidase inhibitor, respectively. Time course experiments of single-cell assays based on the fluorescent probe dichlorofluorescein showed that the generation of H(2)O(2) was dependent on ABA concentration and an increase in the fluorescence intensity of the chloroplast occurred significantly earlier than within the other regions of guard cells. The ABA-induced change in fluorescence intensity in guard cells was abolished by the application of CAT and DPI. In addition, ABA microinjected into guard cells markedly induced H(2)O(2) production, which preceded stomatal closure. These effects were abolished by CAT or DPI micro-injection. Our results suggest that guard cells treated with ABA may close the stomata via a pathway with H(2)O(2) production involved, and H(2)O(2) may be an intermediate in ABA signaling.

Abscisic Acid↗