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Biomedical subjects

F Zhang

Publications and source records attributed to F Zhang.

At least 181 records · Page 10Linked to original sources
PubMed2000

Photoreactivity of 2-pyridones with furan, benzene, and naphthalene. Inter- and intramolecular photocycloadditions.

Pyridones, well-known for their ability to photodimerize, have been found to undergo [4 + 4] photocycloaddition with furan and naphthalene but not with benzene. In some cases these reactions can be highly regio- and stereospecific. Intramolecular reaction with furan produces both cis and trans [4 + 4] products. The cycloaddition with naphthalene can occur both inter- and intramolecularly. The intermolecular reaction yields primarily the cis isomer, whereas the trans isomer is the major product from the intramolecular reaction. A mixture of 4-methoxy-2-pyridone and 2-methoxynaphthalene that could form up to eight regio- and stereoisomers forms largely one [4 + 4] product.

Benzene↗
PubMed2000

Benzo[a]pyrene induces the transcription of cyclooxygenase-2 in vascular smooth muscle cells. Evidence for the involvement of extracellular signal-regulated kinase and NF-kappaB.

Polycyclic aromatic hydrocarbons, such as benzo[a]pyrene (B[a]P) present in tobacco smoke and tar, have been implicated in the development of atherosclerosis as well as cancer. Increased expression of cyclooxygenase-2 (COX-2) has been detected both in atherosclerotic lesions and in epithelial cancers. To determine whether polycyclic aromatic hydrocarbons might directly affect COX expression in vascular cells, we investigated the effects of B[a]P on COX-2 expression in human and rat arterial smooth muscle cells (SMC). Treatment with B[a]P increased levels of COX-2 protein and mRNA and enhanced prostaglandin synthesis. Nuclear runoff assays and transient transfections revealed increased COX-2 gene transcription after treatment with B[a]P. Experiments were done to define the signaling mechanism by which B[a]P induced COX-2. B[a]P caused a rapid increase in phosphorylation of extracellular signal-regulated kinase (ERK); pharmacologic inhibition of mitogen-activated protein kinase kinase blocked B[a]P-mediated induction of COX-2. Depletion of the intracellular antioxidant, glutathione, with buthionine sulfoximine significantly increased B[a]P-mediated induction of COX-2 while exposure to N-acetylcysteine, a precursor of glutathione, suppressed the induction of COX-2 by B[a]P. Several lines of evidence suggest that the induction of COX-2 by B[a]P is mediated, at least in part, by NF-kappaB. Treatment with B[a]P increased binding of NF-kappaB to DNA. Moreover, B[a]P-mediated stimulation of COX-2 promoter activity was blocked when a construct containing a mutagenized NF-kappaB site was used. Pharmacological inhibitors of NF-kappaB blocked the induction of COX-2 protein and the stimulation of COX-2 promoter activity by B[a]P. Taken together, these data are likely to be important for understanding the atherogenic effects of tobacco smoke.

Animals↗
PubMed2000

Combinatorial analysis of the structural requirements of the Escherichia coli hemolysin signal sequence.

We have investigated the substrate specificity of the Escherichia coli hemolysin transporter system. Translocation of hemolysin is dependent on a C-terminal signal sequence located within the last 60 amino acids of this protein. Previous comparative studies of the signal sequence have revealed a conserved helix(alpha1)-linker-helix(alpha2) motif, suggesting that secondary structure is important for transport. In this study, we generated three random libraries in the alpha1, linker, and alpha2 regions, as well as an alpha1-amphiphilic helical library to identify features buried within the structural motif that contribute to transport. Combinatorial variants were generated by altering the primary sequence of specific regions, and correlation between the genotype and phenotype of the mutant populations allowed us to objectively identify any functional features involved. It was found that the alpha1-amphiphilic helix and the linker are both important for function. To our surprise, the second helix of the conserved structural motif was not essential for transport. The finding that a predicted amphiphilic helix and hydrophobicity, rather than primary sequence, contribute to transport in the alpha1 region allows us to speculate on the mechanism of multiple substrate recognition. This may have implications for understanding the broad substrate specificity common among other ATP-binding cassette transporters.

Amino Acid Motifs↗
PubMed2000

Sp1 binding is critical for promoter assembly and activation of the MCP-1 gene by tumor necrosis factor.

The monocyte chemoattractant protein-1 gene (MCP-1) is induced by the inflammatory cytokine tumor necrosis factor through the coordinate assembly of an NF-kappaB-dependent distal regulatory region and a proximal region that has been suggested to bind Sp1 as well as other factors. To provide a genetic correlation for Sp1 activity in this system, a cell line homozygous for a targeted truncation of the Sp1 gene was derived and examined. We found that the lack of Sp1 binding activity resulted in the inability of both the distal and proximal regions to assemble in vivo even though the binding of NF-kappaB to distal region DNA was unaffected in vitro. We also found that Sp1 and NF-kappaB were the minimal mammalian transcription factors required for efficient activity when transfected into Drosophila Schneider cells. Additionally, Sp3 was able to compensate for Sp1 in the Drosophila tissue cell system but not in the Sp1(-/-) cell line suggesting that Sp1 usage is site-specific and is likely to depend on the context of the binding site. Together, these data provide genetic and biochemical proof for Sp1 in regulating the MCP-1 gene.

3T3 Cells↗
PubMed2000

Efficacy of olanzapine in acute bipolar mania: a double-blind, placebo-controlled study. The Olanzipine HGGW Study Group.

BACKGROUND: We compared the efficacy and safety of olanzapine vs placebo for the treatment of acute bipolar mania. METHODS: Four-week, randomized, double-blind, parallel study. A total of 115 patients with a DSM-IV diagnosis of bipolar disorder, manic or mixed, were randomized to olanzapine, 5 to 20 mg/d (n = 55), or placebo (n = 60). The primary efficacy measure was the Young-Mania Rating Scale (Y-MRS) total score. Response and euthymia were defined, a priori, as at least a 50% improvement from baseline to end point and as a score of no less than 12 at end point in the Y-MRS total score, respectively. Safety was assessed using adverse events, Extrapyramidal Symptom (EPS) rating scales, laboratory values, electrocardiograms, vital signs, and weight change. RESULTS: Olanzapine-treated patients demonstrated a statistically significant greater mean (+/- SD) improvement in Y-MRS total score than placebo-treated patients (-14.8 +/- 12.5 and -8.1 +/- 12.7, respectively; P<.001), which was evident at the first postbaseline observation 1 week after randomization and was maintained throughout the study (last observation carried forward). Olanzapine-treated patients demonstrated a higher rate of response (65% vs 43%, respectively; P =.02) and euthymia (61% vs 36%, respectively; P =. 01) than placebo-treated patients. There were no statistically significant differences in EPSs between groups. However, olanzapine-treated patients had a statistically significant greater mean (+/- SD) weight gain than placebo-treated patients (2.1 +/- 2.8 vs 0.45 +/- 2.3 kg, respectively) and also experienced more treatment-emergent somnolence (21 patients [38.2%] vs 5 [8.3% ], respectively). CONCLUSION: Olanzapine demonstrated greater efficacy than placebo in the treatment of acute bipolar mania and was generally well tolerated.

Acute Disease↗
PubMed2000

Free vascularized fibular bone flap in the rat.

Free vascularized fibula bone flap has been widely used in reconstruction of the mandible, long segment defect, congenital pseudarthroses, and osteomyelitis. Such applications stirred an interest in basic studies of bone biology, bone healing process, and incorporation of recipient bone defect. An experimental free vascularized fibula rat model is presented here for such investigations. We performed 16 angiograms and anatomic dissections in eight rats for collecting data on fibular length, blood supply, and the caliber of significant vessels. The fibula was harvested with part of the flexor hallucis longus muscle with an average length of 28 mm. The pedicle can be taken in continuity with the popliteal vessels (average diameter of 0.8 mm and 0.9 mm of artery and vein, respectively, with an average pedicle length of 14 mm). This vascularized fibula bone was harvested and transferred to the groin area of the same rat and anastomosed to the saphenous vessels. Twelve transplantations were performed, with a 7-day flap survival rate of 100%. The free fibula vascularized bone flap in the rat is a reliable model for further investigations.

Animals↗
PubMed2000

Learning curve of microvascular venous anastomosis: a never ending struggle?

In this study, a simple protocol based on the rat femoral venous anastomosis was established to provide a quantitative representation of the progress. The learning curve is based on the patency rate in each consecutive group of five anastomoses. Two groups of surgeons were observed. The inexperienced group encountered a tough time in the first 25 anastomoses. However, the progress was fast and is represented by the steep slope of the curve. A plateau was reached whereby the avearge patency rate matches that of the experienced group. As expected, there was no learning curve for the experienced group. Despite every effort to attempt to maintain a perfect 100% patency on this model, the best achievable patency was only 88%. The results and its implication are discussed.

Anastomosis, Surgical↗
PubMed2000

Temporo-spatial distribution of endothelial-monocyte activating polypeptide II, an anti-angiogenic protein, in the mouse embryo.

We describe the temporo-spatial distribution of Endothelial-Monocyte Activating Polypeptide (EMAP) II in order to better understand what role this anti-angiogenic proteins may play in fetal development. In situ hybridization, immunohistochemistry, and Western analysis were performed on fetal, neonatal, and adult tissue. EMAP II was first detected only within the central nervous system on 9 days postcoitum (dpc). Subsequently, at 11 through 18 dpc, EMAP II expression was detected in the respiratory, central nervous, cardiovascular, urogenital systems, sense organs, and digestive tract. EMAP II mRNA and protein was localized to the epithelium, with its highest expression in neurons, blood vessels, and at sites of epithelial-mesenchymal interaction. The temporo-spatial distribution of EMAP II suggests that it could play an important role in morphogenesis of the vertebrate embryo.

Angiogenesis Inhibitors↗
PubMed2000

Human T lymphocyte genetic modification with naked DNA.

Endowing T lymphocytes with novel functional attributes by genetic modification is under development for a broad range of clinical cellular immunotherapy applications. To circumvent many of the limitations associated with viral vector systems, a plasmid-based electroporation system that reliably generates G418-resistant primary human T lymphocyte clones was developed. TCR alpha/beta+ CD4+CD8-, and CD4-CD8+ T lymphocyte clones can be routinely isolated from OKT3-stimulated peripheral blood mononuclear cells electroporated with linear plasmid DNA in a limiting dilution drug selection format. Fluorescence in situ hybridization (FISH) studies performed on T cell metaphase spreads using a probe specific for plasmid sequence demonstrated a single FISH signal doublet that varied in chromosomal location from clone to clone. Southern blot analysis using a Neo-specific probe verified chromosomal integration of plasmid vector at a single site. Band intensity quantitation of blots developed with a zeta-specific probe capable of annealing to both endogenous TCR-zeta and the introduced chimeric zeta sequence demonstrated that integrated plasmid was present at a single copy number. Expression levels of the CD20-specific chimeric immunoreceptor construct from a CMV immediate/early promoter present in the plasmid vector varied widely from clone to clone but remained stable during ex vivo expansion to cell numbers in excess of 10(10). This T lymphocyte genetic modification strategy is currently being piloted in a FDA-sanctioned adoptive therapy trial for recurrent lymphoma.

CD4-Positive T-Lymphocytes↗
PubMed2000

Comparison of university of wisconsin, euro-collins, low-potassium dextran, and krebs-henseleit solutions for hypothermic lung preservation.

OBJECTIVE: We sought to test the effectiveness of 4 different solutions for hypothermic rat lung preservation. METHODS: One hundred ninety-two rats were used. The rats were divided into 4 groups, and University of Wisconsin, Euro-Collins, low-potassium dextran, or Krebs-Henseleit solution was used in each group. They were further divided into 6 subgroups of 8 rats each. The lungs were preserved at 4 degrees C for 0, 4, 6, 8, 12, or 24 hours, respectively, and lung function was studied by using a living rat perfusion model. RESULTS: Pulmonary arterial flow decreased in each group after 4 to 6 hours of preservation; the low-potassium dextran group decreased the least and the Krebs-Henseleit group decreased the most. Pulmonary vascular resistance increased in each group after 6 hours of preservation; the Krebs-Henseleit group increased the most. Although airway pressure increased, static lung compliance and gas exchange capacity decreased after 8 hours of preservation; the Krebs-Henseleit group exhibited the worst values. Lung tissue wet/dry weight ratio increased gradually during preservation; the University of Wisconsin group exhibited the least increase. An ultrastructural study indicated the least morphologic changes in the low-potassium dextran group at 24 hours. CONCLUSIONS: At 4 degrees C, all solutions preserved rat lungs for 4 hours with acceptable function. However, 6 hours of preservation resulted in damaged pulmonary function in some lungs, and this damage increased when preservation time was extended. The lungs preserved in low-potassium dextran solution had the best overall function, but the lungs preserved in University of Wisconsin solution had less edema.

Adenosine↗
PubMed2000

Iridoids from Dunnia sinensis.

A plumieride type iridoid glucoside, dunnisinoside, and a non-glucosidic iridoid, dunnisinin, were isolated from the leaves of Dunnia sinensis. Their structures were established by 1D and 2D NMR and FABMS experiments.

Anti-Inflammatory Agents↗
PubMed2000

Measurement of ultrasonic power and electro-acoustic efficiency of high power transducers.

In this paper, an improved method for the measurement of acoustic power and electro-acoustic efficiency of high power ultrasonic transducers is presented. The measuring principle is described, the experimental results are given. In comparison with traditional methods, the method presented in this paper has the advantages of simplicity, economy and practicality. The most important is that it can measure the output acoustic power and the electro-acoustic efficiency of the transducer under the condition of high power and practical applications, such as ultrasonic cleaning and soldering.

Electricity↗
PubMed2000

Laboratory and field studies of an antigen capture ELISA for bluetongue virus.

An improved bluetongue antigen capture ELISA (BTACE) technique was evaluated for its ability to detect the full range of 24 bluetongue (BLU) serotypes. The BTACE detected all 24 serotypes in cell culture fluids, including eight serotypes where the representative strains originated from both Australia and also from the South African reference collection. The amount of infectious virus required to obtain a positive BTACE result varied between 100-1000 TCID50. This was approximately 10-fold more sensitive than the antigen capture test described previously (Hosseini, M., Hawkes, R.A., Kirkland, P.D., Dixon, R., 1998. J. Virol. Methods 75, 39-46.). The BTACE method was compared with conventional passage in cell culture to detect the presence of virus in the tissues of embryonated chicken eggs (ECEs) which had been inoculated intravenously with the blood of sheep and cattle infected experimentally with the eight Australian serotypes of BLU (1, 3, 9, 15, 16, 20, 21, and 23). The BTACE method was at least as sensitive as the conventional cell culture detecting virus in ECEs, obviating the need for prolonged cell culture passage to detect the virus. A comparison of the amount of antigen detected in different embryo tissues indicated that liver homogenates gave the highest positive to negative ratios in the BTACE and were selected as the specimen of choice. In studies of sheep infected with all 24 South African reference BLU serotypes this new BTACE was able to detect viraemia with all serotypes. Finally, the BTACE was validated in surveillance programs for BLU in both New South Wales, Australia and in Yunnan Province, People's Republic of China. Blood samples from sentinel cattle were inoculated into ECEs. Homogenised ECE livers were tested by BTACE and those positive were passaged subsequently in cell culture for virus isolation and identification. This protocol led to the efficient isolation of field isolates of many serotypes. The high sensitivity and broad reactivity of the method indicates that it should be valuable for BLU diagnosis and surveillance programs.

Animals↗
PubMed2000

Chronic myelogenous leukemia primitive hematopoietic progenitors demonstrate increased sensitivity to growth factor-induced proliferation and maturation.

We investigated whether primary chronic myelogenous leukemia (CML) hematopoietic progenitors demonstrated altered proliferation and maturation in response to growth factor (GF) stimulation. The effect of GF stimulation on proliferation and expansion of committed and primitive progenitors (colony forming cells [CFC]) was evaluated. Culture of CML and normal CD34(+) cells with different GF for 7 days resulted in similar expansion of committed progenitors (CFC). In contrast, GF culture conditions that expanded normal primitive progenitors (week-6 long-term culture-initiating cells (LTC-IC)] led to depletion of CML LTC-IC numbers. GF culture also resulted in increased depletion of week-10 extended LTC-IC, which represent an even more primitive progenitor population, from CML compared with normal CD34(+) cells. CML CD34(+) cells enter into cycle more quickly than normal CD34(+) cells and CML CFC expansion was accelerated compared to normal CFC. Evaluation of primitive progenitor proliferation using PKH-26 and single-cell LTC-IC analysis demonstrated that the majority of CML LTC-IC remaining after GF culture originated from divided CD34(+) cells, whereas GF-cultured normal LTC-IC were derived mainly from undivided cells. Depletion of CML primitive progenitor numbers in association with increased proliferation suggests increased sensitivity to GF-induced maturation. These studies indicate that CML primitive progenitors have enhanced sensitivity to GF-induced cell division and maturation. Altered GF responsiveness may contribute to abnormal expansion of malignant myeloid cells in CML. These findings may also be applied toward the development of novel approaches to select benign stem cells in CML.

Antigens, CD34↗
PubMed2000

Endothelial monocyte activating polypeptide II inhibits lung neovascularization and airway epithelial morphogenesis.

Neovascularization is crucial to lung development and is mediated through a variety of angiogenic and anti-angiogenic factors. Herein, we show that excess Endothelial Monocyte Activating Polypeptide (EMAP) II, an anti-angiogenic protein, not only inhibits fetal lung neovascularization, but also significantly alters airway epithelial morphogenesis. In a murine allograft model of lung neovascularization and morphogenesis, embryonic lungs transplanted under the skin of immunocompromised mice receiving intraperitoneal EMAP II, had a 56% reduction in vessel density (P<0.0001) compared to control. EMAP II treated lung transplants also exhibited a marked alteration in lung morphogenesis, including lack of type II alveolar cell formation, determined by markedly decreased expression of surfactant protein C, and increased apoptosis. In contrast, lung implants in animals receiving an EMAP II blocking antibody had an increase in vessel density of 50% (P<0.0001) and increased expression of surfactant protein C mRNA in distal epithelium. These studies demonstrate that EMAP II negatively modulates lung neovascularization as well as leading to the arrest of lung airway epithelial morphogenesis and apoptosis.

Angiogenesis Inhibitors↗
PubMed2000

Murine hoxd4 expression in the CNS requires multiple elements including a retinoic acid response element.

We have identified a retinoic acid response element (RARE) within a neural enhancer located 3' to the Hoxd4 gene. This RARE is required for the initiation and maintenance of Hoxd4 transgene expression in neurectoderm, and for full anteriorized expression upon retinoic acid (RA) treatment. Mutations within the sequence TTTTCTG, located 2 bp downstream of the RARE, posteriorized transgene activity. However, the onset of transgene expression and its response to RA were indistinguishable from wild type. While the TTTTCTG motif resembles a CDX binding site, human CDX1 protein did not interact with this element in vitro. Three additional regions were also shown to control transgene expression in neurectoderm, establishing that multiple elements constitute the Hoxd4 neural enhancer.

Animals↗
PubMed2000

Fructose-1,6-diphosphate and a glucose-free solution enhances functional recovery in hypothermic heart preservation.

BACKGROUND: Fructose-1,6-diphosphate (FDP) has been shown to protect tissue during hypoxia under various ischemic conditions, including isolated heart perfusion. We tested the hypothesis that adding FDP to St. Thomas solution can extend hypothermic heart preservation time. METHODS: Sixteen adult Sprague-Dawley rats were used. Under general anesthesia, the hearts were removed and preserved at 4 degrees C in St. Thomas solution (30 ml/kg) for 12 hours. FDP (5 mM) was added to the St. Thomas solution in the study group (n = 8), whereas no FDP was used in the control group (n = 10). The hearts were reperfused after 12 hours of preservation using a working heart model. RESULTS: In the study group, cardiac output ranged from 13.00 +/- 2.34 to 17.66 +/- 1.71 ml/min, maximum aortic flow was 3.40 +/- 1.99 to 9.26 +/- 1.72 ml/min, left ventricular stroke volume ranged from 0.074 +/- 0.014 to 0.092 +/- 0.009 ml, left ventricular stroke work ranged from 6.22 +/- 0.39 to 7.95 +/- 0.44 ml/mmHg, and maximum left ventricular generated power was 14.38 +/- 2.94 to 20.16 +/- 2.49 Joules/min. All of these parameters were higher than those in the control group (p < 0.001). Coronary vascular resistance and myocardial tissue wet/dry weight ratio were lower in the study group than in the control group (p < 0.05). CONCLUSIONS: Heart function was better preserved when FDP was added to St. Thomas solution during hypothermic rat heart preservation. The mechanism is not totally clear, but enhancement of high-energy phosphate production during ischemia is possible. Key words: heart, procurement, hypothermia, fructose-1,6-diphosphate.

Animals↗