@article {2401, title = {Arabidopsis LTPG Is a Glycosylphosphatidylinositol-Anchored Lipid Transfer Protein Required for Export of Lipids to the Plant Surface}, journal = {Plant Cell}, volume = {21}, number = {4}, year = {2009}, note = {ISI Document Delivery No.: 448XRTimes Cited: 13Cited Reference Count: 42DeBono, Allan Yeats, Trevor H. Rose, Jocelyn K. C. Bird, David Jetter, Reinhard Kunst, Ljerka Samuelsa, Lacey}, month = {Apr}, pages = {1230-1238}, type = {Article}, abstract = {Plant epidermal cells dedicate more than half of their lipid metabolism to the synthesis of cuticular lipids, which seal and protect the plant shoot. The cuticle is made up of a cutin polymer and waxes, diverse hydrophobic compounds including very-long-chain fatty acids and their derivatives. How such hydrophobic compounds are exported to the cuticle, especially through the hydrophilic plant cell wall, is not known. By performing a reverse genetic screen, we have identified LTPG, a glycosylphosphatidylinositol-anchored lipid transfer protein that is highly expressed in the epidermis during cuticle biosynthesis in Arabidopsis thaliana inflorescence stems. Mutant plant lines with decreased LTPG expression had reduced wax load on the stem surface, showing that LTPG is involved either directly or indirectly in cuticular lipid deposition. In vitro 2-p-toluidinonaphthalene-6-sulfonate assays showed that recombinant LTPG has the capacity to bind to this lipid probe. LTPG was primarily localized to the plasma membrane on all faces of stem epidermal cells in the growing regions of inflorescence stems where wax is actively secreted. These data suggest that LTPG may function as a component of the cuticular lipid export machinery.}, keywords = {ABC TRANSPORTER, BINDING, CELLS, CUTICULAR WAX, GENE, GENOME-WIDE, MEMBRANE-PROTEINS, PHOSPHOLIPASE-D, PREDICTION SERVER, SEQUENCE TAGS}, isbn = {1040-4651}, url = {://000266295800020}, author = {DeBono, A. and Yeats, T. H. and Rose, J. K. C. and Bird, D. and Jetter, R. and Kunst, L. and Samuelsa, L.} } @article {2396, title = {Binding and Uptake of RGD-Containing Ligands to Cellular alpha(v)beta(3) Integrins}, journal = {International Journal of Peptide Research and Therapeutics}, volume = {15}, number = {1}, year = {2009}, note = {ISI Document Delivery No.: 430WTTimes Cited: 2Cited Reference Count: 34Cressman, Sonya Sun, Ying Maxwell, E. Jane Fang, Ning Chen, David D. Y. Cullis, Pieter R.}, month = {Mar}, pages = {49-59}, type = {Article}, abstract = {The cyclic peptide, cRGDf[N(me)]V, binds to the alpha(v)beta(3) integrin and can disrupt binding of the integrin to its natural ligands in the extracellular matrix. In this work, the ability of a water-soluble, fluorescently labeled variant of the RGD-containing peptide (cRGDfK-488) to bind to integrins on human umbilical vascular endothelial cells (HUVEC) and subsequently undergo endocytosis was characterized. This information was compared to the binding and uptake properties of an alpha(v)beta(3) integrin-specific monoclonal antibody, LM609X. The specificity of the RGD-containing peptide is assessed by comparison with control peptide that does not bind to the alpha(v)beta(3) integrin, cRADfK-488. Using a high purity construct, it is shown that the RGD ligand exhibits dissociation constants in the micromolar range whereas LM609X exhibits dissociation constants in the nanomolar range. However, the RGD ligand showed greater uptake following incubation at temperatures which permit endocytosis. A 7.4-fold increase in uptake of the RGD peptide was observed following a 1 h incubation with HUVEC at 37 degrees C (an endocytosis permissive temperature), as compared to that at 4 degrees C (an endocytosis prohibitive temperature). In contrast, only a 1.9-fold increase in cell-associated fluorescence was observed for similar incubations with LM609X. Results from fluorescence microscopy supports the notion that the RGD peptide is rapidly endocytosed at 37 degrees C as compared to LM609X. These results are discussed with regard to previous work indicating that RGD ligands enter cells by integrin-independent pathways. These studies provide well-controlled measures of how RGD ligands stimulate endocytosis. This may be of considerable interest for intracellular delivery of ligand-associated drugs in anti-angiogenic applications.}, keywords = {alpha(v)beta(3) integrins, ALPHA-V-BETA-3, ANGIOGENESIS, ANTAGONISTS, ANTITUMOR EFFICACY, CELLS, Endocytosis, EXPRESSION, IN-VIVO, PEPTIDES, RGD, TARGETED DRUG-DELIVERY, TUMOR VASCULATURE}, isbn = {1573-3149}, url = {://000265022900007}, author = {Cressman, S. and Sun, Y. and Maxwell, E. J. and Fang, N. and Chen, D. D. Y. and Cullis, P. R.} } @article {2376, title = {Plectosphaeroic Acids A, B, and C, Indoleamine 2,3-Dioxygenase Inhibitors Produced in Culture by a Marine Isolate of the Fungus Plectosphaerella cucumerina}, journal = {Organic Letters}, volume = {11}, number = {14}, year = {2009}, note = {ISI Document Delivery No.: 472NMTimes Cited: 1Cited Reference Count: 29Carr, Gavin Tay, Wendy Bottriell, Helen Andersen, Sarah K. Mauk, A. Grant Andersen, Raymond J.}, month = {Jul}, pages = {2996-2999}, type = {Article}, abstract = {Laboratory cultures of the fungus Plectosphaerella cucumerina obtained from marine sediments collected in Barkley Sound, British Columbia, yielded the novel alkaloids plectosphaeroic acids A (1) to C (3). The alkaloids 1-3 are inhibitors of indoleamine 2,3-dioxygenase (IDO).}, keywords = {CANCER, CELLS, chemotherapy, EXIGUAMINE-A, EXPRESSION, IDO, MECHANISM, METABOLITES, SUPPRESSION, TRYPTOPHAN DEGRADATION}, isbn = {1523-7060}, url = {://000268138800011}, author = {Carr, G. and Tay, W. and Bottriell, H. and Andersen, S. K. and Mauk, A. G. and Andersen, R. J.} } @article {2298, title = {Biomimetic synthesis of the IDO inhibitors exiguamine A and B}, journal = {Nature Chemical Biology}, volume = {4}, number = {9}, year = {2008}, note = {ISI Document Delivery No.: 339SNTimes Cited: 7Cited Reference Count: 19Volgraf, Matthew Lumb, Jean-Philip Brastianos, Harry C. Carr, Gavin Chung, Marco K. W. Muenzel, Martin Mauk, A. Grant Andersen, Raymond J. Trauner, Dirk}, month = {Sep}, pages = {535-537}, type = {Article}, abstract = {Biomimetic synthesis is an attempt to assemble natural products along biosynthetic lines without recourse to the full enzymatic machinery of nature. We exemplify this with a total synthesis of exiguamine A and the newly isolated natural product exiguamine B. The most noteworthy feature of this work is an oxidative endgame drawing from the complex chemistry of catecholamines, which allows for ready access to a new class of nanomolar indoleamine-2,3-dioxygenase inhibitors.}, keywords = {3-DIOXYGENASE, ANALOGS, CANCER, CASCADE, CELLS, ELECTROCYCLIZATIONS, EXPRESSION, INDOLEAMINE 2}, isbn = {1552-4450}, url = {://000258597700011}, author = {Volgraf, M. and Lumb, J. P. and Brastianos, H. C. and Carr, G. and Chung, M. K. W. and Munzel, M. and Mauk, A. G. and Andersen, R. J. and Trauner, D.} } @article {2037, title = {Synthesis of indoleamine 2,3-dioxygenase inhibitory analogues of the sponge alkaloid exiguamine A}, journal = {Journal of Medicinal Chemistry}, volume = {51}, number = {9}, year = {2008}, note = {ISI Document Delivery No.: 295USTimes Cited: 17Cited Reference Count: 20Carr, Gavin Chung, Marco K. W. Mauk, A. Grant Andersen, Raymond J.}, month = {May}, pages = {2634-2637}, type = {Article}, abstract = {Synthetic analogues of the sponge natural product exiguamine A (3) have been prepared and evaluated for their ability to inhibit indoleamine 2,3-dioxygenase in vitro.}, keywords = {CANCER, CATABOLISM, CELLS, chemotherapy, EXPRESSION, IDO, IMMUNE TOLERANCE, MECHANISM, SMALL-MOLECULE INHIBITORS, TRYPTOPHAN DEGRADATION}, isbn = {0022-2623}, url = {://000255500000008}, author = {Carr, G. and Chung, M. K. W. and Mauk, A. G. and Andersen, R. J.} } @article {1148, title = {Ceratamines, structurally simple microtubule-stabilizing antimitotic agents with unusual cellular effects}, journal = {Cancer Research}, volume = {65}, number = {8}, year = {2005}, note = {ISI Document Delivery No.: 916ZFTimes Cited: 14Cited Reference Count: 9}, month = {Apr}, pages = {3040-3043}, type = {Article}, abstract = {Ceratamine A and ceratamine B are heterocyclic alkaloids recently identified in a screen for compounds that arrest cells in mitosis. Treatment of breast carcinoma MCF-7 cells causes a concentration-dependent block of cell cycle progression exclusively at mitosis. In vitro studies with purified tubulin indicate that the ceratamines directly stimulate microtubule polymerization in the absence of microtubule-associated proteins. Cells treated with ceratamines show a dense perinuclear microtubule network in interphase and multiple pillar-like tubulin structures in mitotic cells. The ceratamines do not compete with paclitaxel for binding to microtubules in vitro. Unlike other microtubule-stabilizing agents, the ceratamines have simple structures with no chiral centers, making them attractive drug leads.}, keywords = {BIND, CELLS, RESISTANT, TAXOID SITE, TUBULIN}, isbn = {0008-5472}, url = {://000228424800012}, author = {Karjala, G. and Chan, Q. and Manzo, E. and Andersen, R. J. and Roberge, N.} } @article {1307, title = {Synthesis of pelorol and analogues: Activators of the inositol 5-phosphatase SHIP}, journal = {Organic Letters}, volume = {7}, number = {6}, year = {2005}, note = {ISI Document Delivery No.: 906DPTimes Cited: 19Cited Reference Count: 18}, month = {Mar}, pages = {1073-1076}, type = {Article}, abstract = {A screening program designed to find new antiinflammatory agents has identified the sponge meroterpenoid pelorol (1) as an in vitro activator of the inositol-5-phosphatase SHIP. Pelorol (1) and several functional group analogues have been synthesized from sclareolide (4).}, keywords = {CELLS, METABOLITE, MICE, SPONGE DACTYLOSPONGIA-ELEGANS}, isbn = {1523-7060}, url = {://000227621000030}, author = {Yang, L. and Williams, D. E. and Mui, A. and Ong, C. and Krystal, G. and Van Soest, R. and Andersen, R. J.} } @article {1010, title = {Complementary inhibition of synoviocyte, smooth muscle cell or mouse lymphoma cell proliferation by a vanadyl curcumin complex compared to curcumin alone}, journal = {Journal of Inorganic Biochemistry}, volume = {98}, number = {12}, year = {2004}, note = {ISI Document Delivery No.: 876VBTimes Cited: 20Cited Reference Count: 62}, month = {Dec}, pages = {2063-2070}, type = {Article}, abstract = {A novel vanadyl curcumin complex (VO(cur)2) has been synthesized and and its physicochemical properties characterized. Biological characterization included in vitro testing for anti-rheumatic activity in synoviocytes, angiogenesis inhibition in smooth muscle cells and anti-cancer potential in mouse lymphoma cells; as well as in vivo testing for hypoglycemic activity by oral gavage in streptozotocin (STZ)-diabetic rats. VO(cur)2 was more effective as an anti-cancer agent, compared to uncomplexed curcumin or vanadyl ion alone, was more than twice as effective as curcumin alone as an anti-arthritic agent, and was more than four times as effective as curcumin alone in inhibiting smooth muscle cell proliferation. In both acute and chronic screening tests, VO(cur)2 was ineffective as an insulin mimetic agent; however, it also proved to be exceptionally non-toxic, with no evidence of negative symptornatology during a month-long treatment period, at doses up to and including 2.0 mmol kg(-1) day(-1). (C) 2004 Elsevier Inc. All rights reserved.}, keywords = {antioxidant, apoptosis, arthritis lymphoma, BIS(MALTOLATO)OXOVANADIUM(IV), CELLS, COMPLEX, COORDINATION, curcurnin, DIABETIC-RATS, DIFERULOYL METHANE CURCUMIN, FREE-RADICALS, INDUCED LIPID-PEROXIDATION, INSULIN MIMICS, LEUKEMIA HL-60, METAL-IONS, OXIDATIVE STRESS, vanadyl ion}, isbn = {0162-0134}, url = {://000225525200010}, author = {Thompson, K. H. and Bohmerle, K. and Polishchuk, E. and Martins, C. and Toleikis, P. and Tse, J. and Yuen, V. and McNeill, J. H. and Orvig, Chris} } @article {626, title = {Optimization of cellular nucleotide extraction and sample preparation for nucleotide pool analyses using capillary electrophoresis}, journal = {Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences}, volume = {788}, number = {1}, year = {2003}, note = {ISI Document Delivery No.: 664KCTimes Cited: 12Cited Reference Count: 28}, month = {May}, pages = {103-111}, type = {Article}, abstract = {Cell extraction and further sample preparation for nucleotide pool analysis using capillary electrophoresis was faster and simpler using volatile extraction solvents (e.g. organic solvents and de-ionized water) compared to the commonly applied acids dissolved in water (e.g. perchloric acid and trichloracetic acid). Temperature had to be controlled during the whole sample preparation process to prevent degradation, and extracts had to be cleaned from proteins and other large molecules prior to capillary electrophoretic analysis to improve reproducibility. Capillary electrophoresis using borate and cyclodextrins in the background electrolyte was used for determining 11 cellular nucleotides simultaneously. In order to optimize the assay, 0-100\% acetonitrile, 0-100\% ethanol, and 0-100\% methanol in de-ionized water were applied to extract nucleotides from mouse lymphoma cells, and nucleotide yields, recovery, and reproducibility were compared. The assay met the commonly accepted validation limits for biological fluids, if 20-80\% acetonitrile in water and 40-60\% ethanol in water were used as extraction solvents. (C) 2003 Elsevier Science B.V. All rights reserved.}, keywords = {CELLS, dynamic pH junction, FLUIDS, MIGRATION BEHAVIOR, NUCLEOSIDES, nucleotides, PERFORMANCE LIQUID-CHROMATOGRAPHY, QUANTITATIVE-ANALYSIS, SEPARATION, TISSUES, TRIPHOSPHATES}, isbn = {1570-0232}, url = {://000182059400012}, author = {Grob, M. K. and O{\textquoteright}Brien, K. and Chu, J. J. and Chen, D. D. Y.} } @article {5144, title = {Methylated trivalent arsenic species are genotoxic}, journal = {Chemical Research in Toxicology}, volume = {14}, number = {4}, year = {2001}, note = {ISI Document Delivery No.: 424XZTimes Cited: 253Cited Reference Count: 55}, month = {Apr}, pages = {355-361}, type = {Article}, abstract = {The reactivities of methyloxoarsine (MAsIII) and iododimethylarsine (DMAsIII), two methylated trivalent arsenicals, toward supercoiled phi X174 RFI DNA were assessed using a DNA nicking assay. The induction of DNA damage by these compounds in vitro in human peripheral lymphocytes was assessed using a single-cell gel (SCG, "comet") assay. Both methylated trivalent arsenicals were able to nick and/or completely degrade phi X174 DNA in vitro in 2 h incubations at 37 degreesC (pH 7.4) depending on concentration. MAsIII was effective at nicking phi X174 DNA at 30 mM; however, at 150 muM DMAsIII, nicking could be observed. Exposure of (phi X174 DNA to sodium arsenite (iAs(III); from 1 nM up to 300 mM), sodium arsenate (from 1 muM to 1 M), and the pentavalent arsenicals, monomethylarsonic acid (from 1 muM to 3 M) and dimethylarsinic acid (from 0.1 to 300 mM), did not nick or degrade phi X174 DNA under these conditions. In the SCG assay in human lymphocytes, methylated trivalent arsenicals were much more potent than any other arsenicals that were tested. On the basis of the slopes of the concentration-response curve for the tail moment in the SCG assay, MAsIII and DMAsIII were 77 and 386 times more potent than iAs(III), respectively. Because methylated trivalent arsenicals were the only arsenic compounds that were observed to damage naked DNA and required no exogenously added enzymatic or chemical activation systems, they are considered here to be direct-acting forms of arsenic that are genotoxic, though they are not, necessarily, the only genotoxic species of arsenic that could exist.}, keywords = {CELLS, DIMETHYLARSINIC ACID, DRINKING-WATER, ENZYMATIC METHYLATION, FIBROBLASTS, GLUTATHIONE-REDUCTASE, HUMAN, HUMAN URINE, INHIBITION, MONOMETHYLARSONOUS ACID, SODIUM ARSENITE}, isbn = {0893-228X}, url = {://000168260400005}, author = {Mass, M. J. and Tennant, A. and Roop, B. C. and Cullen, W. R. and Styblo, M. and Thomas, D. J. and Kligerman, A. D.} } @article {4901, title = {Monomethylarsonous acid (MMA(III)) is more toxic than arsenite in Chang human hepatocytes}, journal = {Toxicology and Applied Pharmacology}, volume = {163}, number = {2}, year = {2000}, note = {ISI Document Delivery No.: 295TBTimes Cited: 294Cited Reference Count: 28}, month = {Mar}, pages = {203-207}, type = {Article}, abstract = {Methylation has been considered to be the primary detoxication pathway of inorganic arsenic. Inorganic arsenic is methylated by many, but not all animal species, to monomethylarsonic acid (MMA(V)), monomethylarsonous acid (MMA(III)), and dimethylarsinic acid (DMA(V)). The As-V derivatives have been assumed to produce low toxicity, but the relative toxicity of MMA(III) remains unknown. In vitro toxicities of arsenate, arsenite, MMA(V), MMA(III) and DMA(V) were determined in Chang human hepatocytes, Leakage of lactate dehydrogenase (LDH) and intracellular potassium (K+) and mitochondrial metabolism of the tetrazolium salt XTT were used to assess cytotoxicity due to arsenic exposure. The mean LC50 based on LDH assays in phosphate media was 6 mu M for MMA(III) and 68 mu M for arsenite. Using the assay for K+ leakage in phosphate media, the mean LC50 was 6.3 mu M for MMA(III) and 19.8 mu M for arsenite. The mean LC50 based on the XTT assay in phosphate media was 13.6 mu M for MMA(III) and 164 mu M for arsenite. The results of the three cytotoxicity assays (LDH, K+, and XTT) reveal the following order of toxicity in Chang human hepatocytes: MMA(III) > arsenite > arsenate > MMA(V) = DMA(V). Data demonstrate that MMA(III) an intermediate in inorganic arsenic methylation, is highly toxic and again raises the question as to whether methylation of inorganic arsenic is a detoxication process. (C) 2000 Academic Press.}, keywords = {ARSENATE, ARSENITE, ASSAY, CELLS, Chang human hepatocytes, DIMETHYLARSINIC ACID, DMA, DMA(V), DMPS, ENZYMATIC METHYLATION, LDH, LIVER, MICE, MMA(III), MMA(V), monomethylarsonic acid, MONOMETHYLARSONOUS ACID, POTASSIUM, VIABILITY, XTT}, isbn = {0041-008X}, url = {://000085983000013}, author = {Petrick, J. S. and Ayala-Fierro, F. and Cullen, W. R. and Carter, D. E. and Aposhian, H. V.} } @article {4703, title = {Electrostatically mediated interactions between cationic lipid-DNA particles and an anionic surface}, journal = {Archives of Biochemistry and Biophysics}, volume = {366}, number = {1}, year = {1999}, note = {ISI Document Delivery No.: 202JKTimes Cited: 7Cited Reference Count: 29}, month = {Jun}, pages = {31-39}, type = {Article}, abstract = {In an effort to model the interaction of lipid-based DNA delivery systems with anionic surfaces, such as a cell membrane, we have utilized microelectrophoresis to characterize how electrokinetic measurements can provide information on surface charge and binding characteristics. We have established that cationic lipids, specifically N-N-dioleoyl-N,N-dimethylammonium chloride (DODAC), incorporated into liposomes prepared with I,2-dioleoyl-i-glycero-3-phosphoethanolamine (DOPE) or 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) at 50 mol\%, change the inherent electrophoretic mobility of anionic latex polystyrene beads. Self-assembling lipid-DNA particles (LDPs), prepared at various cationic lipid to negative DNA phosphate charge ratios, effected no changes in bead mobility when the LDP charge ratio (+/-) was equal to or less than 1. Increasing the LDP concentration in a solution of 0.1\% (w/v) anionic beads resulted in a charge reversal effect when a net charge of LDP to total bead charge ratio (+/-) of 1:1 was observed. LDP formulations, utilizing either DOPE or DOPC, showed similar titration profiles with a charge reversal observed at a 1:1 net LDP to bead charge ratio (+/-). It was confirmed through centrifugation studies that the DNA in the LDP was associated with the anionic latex beads through electrostatic interactions. LDP binding, rather than the binding of dissociated cationic lipids, resulted in the observed electrophoretic mobility changes of the anionic latex beads. (C) 1999 Academic Press.}, keywords = {BILAYERS, CELLS, ELECTROSTATIC INTERACTIONS, FUSION, GENE-TRANSFER, lipid-DNA particles, lipoplex, LIPOSOMES, microelectrophoresis, PHOSPHATIDYLETHANOLAMINE, PLASMID DNA, VESICLES}, isbn = {0003-9861}, url = {://000080648400005}, author = {Wong, F. M. P. and Bally, M. B. and Brooks, D. E.} } @article {4659, title = {Measurement of some small-molecule and peptide neurotransmitters in-vitro using a fiber-optic probe with pulsed ultraviolet resonance Raman spectroscopy}, journal = {Journal of Neuroscience Methods}, volume = {92}, number = {1-2}, year = {1999}, note = {ISI Document Delivery No.: 262ADTimes Cited: 13Cited Reference Count: 22}, month = {Oct}, pages = {15-24}, type = {Article}, abstract = {Many techniques have been developed to investigate the chemistry associated with brain activity. These techniques generally fall into two categories: fast techniques with species-limited sensitivity; and generally slower techniques with broader species sensitivity. Therefore, a need exists for a fast, minimally invasive technique that is sensitive to a wide array of biologically relevant compounds in order to measure chemical brain events in real time. The work presented here describes the development of a novel spectroscopic neurotransmitter probe for the rapid and simultaneous detection of a variety of neurotransmitters. A fiber-optic-linked Raman and tunable ultraviolet resonance Raman system was assembled with custom designed optical fiber probes. Using this system, the ultraviolet resonance Raman spectra of some small-molecule and peptide neurotransmitters were measured in-vitro with a fiber-optic probe and are reported here for the first time. The probe has furthermore been used to measure neurotransmitter secretions obtained from depolarized rat pheochromocytoma (PC12) cells. These results demonstrate the general utility of this approach which, due to the fiber-optic implementation, could potentially also be applied to in-vivo neurotransmitter determinations. (C) 1999 Elsevier Science B.V. All rights reserved.}, keywords = {CELLS, fiber, neuropeptide, neurotransmitter, optical, resonance Raman spectroscopy}, isbn = {0165-0270}, url = {://000084042800003}, author = {Schulze, H. G. and Greek, L. S. and Barbosa, C. J. and Blades, M. W. and Gorzalka, B. B. and Turner, R. F. B.} } @article {4659, title = {Measurement of some small-molecule and peptide neurotransmitters in-vitro using a fiber-optic probe with pulsed ultraviolet resonance Raman spectroscopy}, journal = {Journal of Neuroscience Methods}, volume = {92}, number = {1-2}, year = {1999}, note = {ISI Document Delivery No.: 262ADTimes Cited: 13Cited Reference Count: 22}, month = {Oct}, pages = {15-24}, type = {Article}, abstract = {Many techniques have been developed to investigate the chemistry associated with brain activity. These techniques generally fall into two categories: fast techniques with species-limited sensitivity; and generally slower techniques with broader species sensitivity. Therefore, a need exists for a fast, minimally invasive technique that is sensitive to a wide array of biologically relevant compounds in order to measure chemical brain events in real time. The work presented here describes the development of a novel spectroscopic neurotransmitter probe for the rapid and simultaneous detection of a variety of neurotransmitters. A fiber-optic-linked Raman and tunable ultraviolet resonance Raman system was assembled with custom designed optical fiber probes. Using this system, the ultraviolet resonance Raman spectra of some small-molecule and peptide neurotransmitters were measured in-vitro with a fiber-optic probe and are reported here for the first time. The probe has furthermore been used to measure neurotransmitter secretions obtained from depolarized rat pheochromocytoma (PC12) cells. These results demonstrate the general utility of this approach which, due to the fiber-optic implementation, could potentially also be applied to in-vivo neurotransmitter determinations. (C) 1999 Elsevier Science B.V. All rights reserved.}, keywords = {CELLS, fiber, neuropeptide, neurotransmitter, optical, resonance Raman spectroscopy}, isbn = {0165-0270}, url = {://000084042800003}, author = {Schulze, H. G. and Greek, L. S. and Barbosa, C. J. and Blades, M. W. and Gorzalka, B. B. and Turner, R. F. B.} } @article {4647, title = {The structures of the neurotrophin 4 homodimer and the brain-derived neurotrophic factor/neurotrophin 4 heterodimer reveal a common Trk-binding site}, journal = {Protein Science}, volume = {8}, number = {12}, year = {1999}, note = {ISI Document Delivery No.: 266RPTimes Cited: 24Cited Reference Count: 45}, month = {Dec}, pages = {2589-2597}, type = {Article}, abstract = {The neurotrophins are growth factors that are involved in the development and survival of neurons. Neurotrophin release by a target tissue results in neuron growth along the neurotrophin concentration gradient, culminating in the eventual innervation of the target tissue. These activities are mediated through trk cell surface receptors. We have determined the structures of the heterodimer formed between brain-derived neurotrophic factor (BDNF) and neurotrophin 4 (NT4), as well as the structure of homodimer of NT4. We also present the structure of the Neurotrophin 3 homodimer, which is refined to higher resolution than previously published. These structures provide the first views of the architecture of the NT4 protomer. Comparison of the surface of a model of the BDNF homodimer with the structures of the neurotrophin homodimers reveals common features that may be important in the binding between the neurotrophins and their receptors. In particular, there exists an analogous region on the surface of each neurotrophin that is likely to be involved in trk receptor binding. Variations in sequence on the periphery of this common region serve to confer trk receptor specificity.}, keywords = {BDNF, CELLS, CRYSTAL-STRUCTURE, CRYSTALLOGRAPHY, DIFFERENTIATION, nerve growth factor, NERVE GROWTH-FACTOR, NGF, PURIFICATION, RECEPTOR, RECEPTORS, RECOGNITION, SPECIFICITY}, isbn = {0961-8368}, url = {://000084314100005}, author = {Robinson, R. C. and Radziejewski, C. and Spraggon, G. and Greenwald, J. and Kostura, M. R. and Burtnick, L. D. and Stuart, D. I. and Choe, S. and Jones, E. Y.} } @article {4582, title = {Synthesis of new hypoxia markers EF1 and [F-18]-EF1}, journal = {Applied Radiation and Isotopes}, volume = {51}, number = {6}, year = {1999}, note = {ISI Document Delivery No.: 242RBTimes Cited: 23Cited Reference Count: 33}, month = {Dec}, pages = {643-650}, type = {Article}, abstract = {We report on the preparation of a hypoxia marker 2-(2-nitroimidazol-1[H]-yl)-N-(3-fluoropropyl)acetamide (EF1) and its F-18 analog, 2-(2-nitroimidazol-1[H]-yl)-N-(3-[F-18]fluoropropyl)acetamide ([F-18]-EF1). Two methods for the preparation of 3-fluoropropylamine, the EF1 side chain, are described. [F-18]-EF1 was prepared with a radiochemical yield of 2\% by nucleophilic substitution of bromine in 2-(2-nitroimidazol-1[H]-yl)-N-(3-bromopropyl) acetamide (EBrl) by carrier-added F-18 in DMSO at 120 degrees C. Our results demonstrate the preparation of clinically relevant amounts of [F-18]-EF1 for use as a non-invasive hypoxia marker with detection using positron emission tomography (PET). (C) 1999 Elsevier Science Ltd. All rights reserved.}, keywords = {ADDUCTS, CARCINOMA, CELLS, DEPENDENCE, F-18 FLUOROMISONIDAZOLE, IMAGING TUMOR HYPOXIA, INVIVO, ischemia, NONINVASIVE ASSESSMENT, REDUCTION}, isbn = {0969-8043}, url = {://000082954500006}, author = {Kachur, A. V. and Dolbier, W. R. and Evans, S. M. and Shiue, C. Y. and Shiue, G. G. and Skov, K. A. and Baird, I. R. and James, Brian R. and Li, A. R. and Roche, A. and Koch, C. J.} } @article {4190, title = {An effective synthetic route to EF5}, journal = {Synthetic Communications}, volume = {28}, number = {19}, year = {1998}, note = {ISI Document Delivery No.: 117KHTimes Cited: 2Cited Reference Count: 17}, pages = {3701-3709}, type = {Article}, abstract = {EF5 (a 2-nitroimidazole containing an N-(pentafluoropropyl) acetamide substituent) is a very sensitive probe for quantifying the amount of hypoxia within cells; a much improved, short step, synthetic procedure is described for EF5, whose X-ray structure is also presented.}, keywords = {ANTIBODIES, BINDING, CELLS, COMPLEXES, CRYSTAL, HYPOXIA, TUMORS}, isbn = {0039-7911}, url = {://000075780100021}, author = {Baird, I. R. and Skov, K. A. and James, Brian R. and Rettig, S. J. and Koch, C. J.} } @article {4089, title = {Application of long-circulating liposomes to cancer photodynamic therapy}, journal = {Biological \& Pharmaceutical Bulletin}, volume = {20}, number = {6}, year = {1997}, note = {ISI Document Delivery No.: XG547Times Cited: 26Cited Reference Count: 30}, month = {Jun}, pages = {670-673}, type = {Article}, abstract = {Photodynamic therapy (PDT) as a cancer treatment is notable for its quite low side effects in comparison with those of chemotherapy and radiotherapy. However, the accumulation of porphyrin derivatives used in PDT into tumor tissues is rather low. Since long-circulating liposomes are known to accumulate passively into tumor tissues, we liposomalized a porphyrin derivative, benzoporphyrin derivative monoacid ring A (BPD-MA), and used these liposomes to investigate the usefulness of PDT for tumor-bearing mice. BPD-MA was liposomalized into glucuronate-modified liposomes, which are known to be long-circulating. These liposomes were injected i.v. into Balb/c mice bearing Meth A sarcoma, and tumor regression and survival time were monitored after irradiation with laser light. Tumor regression and complete curing of tumor (80\% cure rate by the treatment with 6 mg/kg BPD-R?IA) were observed when long circulating liposomalized BPD-MA was injected and laser-irradiated. In contrast, only a 20\% cure rate was obtained when the animals were treated with BPD-MA solution or BPD-MA entrapped in conventional liposomes. These results suggest that a long-circulating liposomal formulation of photo-sensitive agents is useful for PDT.}, keywords = {BEARING MICE, benzoporphyrin, BENZOPORPHYRIN DERIVATIVES, BPD, CELLS, DERIVATIVE, drug delivery system, EFFICACY, INVIVO, LIPOPROTEINS, liposome, MURINE TUMOR-MODEL, PHOTODYNAMIC THERAPY, PHOTOSENSITIZER, time}, isbn = {0918-6158}, url = {://A1997XG54700016}, author = {Oku, N. and Saito, N. and Namba, Y. and Tsukada, H. and Dolphin, D. and Okada, S.} } @article {3703, title = {Interfacial thickness of liposomes containing poly(ethylene glycol)-cholesterol from electrophoresis}, journal = {Biophysical Journal}, volume = {70}, number = {1}, year = {1996}, note = {ISI Document Delivery No.: TY683Times Cited: 29Cited Reference Count: 33}, month = {Jan}, pages = {313-320}, type = {Article}, abstract = {The electrophoretic mobilities of liposomes incorporating a polyethylene glycol (PEG) headgroup coupled to cholesterol for PEG of average chain index 3.0, 13.2, and 22.3 have been determined as a function of PEG-cholesterol mole fraction between 5\% and 40\% and ionic strength between 2 and 200 mM. The liposome compositions were 40 mole \% cholesterol plus PEG-cholesterol, 10 mole \% 1,2-dipalmitoyl-sn-glyerco-3-phosphoglycerol and 50 mole \% egg phosphatidylcholine. The mobilities were fit to a model in which the PEG forms a surface layer of polymer subject to viscous drag arising I from electroosmotic flow within this layer. The model provides estimates of the average layer thickness that are comparable to those determined from contemporary models of surface-attached polymer.}, keywords = {CELLS, CHAINS, grafted polymer brush, mobility, PARTICLES}, isbn = {0006-3495}, url = {://A1996TY68300026}, author = {Janzen, J. and Song, X. and Brooks, D. E.} } @article {3017, title = {1993 SYNTEX-AWARD LECTURE - PHOTOMEDICINE AND PHOTODYNAMIC THERAPY}, journal = {Canadian Journal of Chemistry-Revue Canadienne De Chimie}, volume = {72}, number = {4}, year = {1994}, note = {ISI Document Delivery No.: NN830Times Cited: 84Cited Reference Count: 47}, month = {Apr}, pages = {1005-1013}, type = {Article}, abstract = {Photodynamic therapy (PDT) involves the treatment of diseased tissue and cells using a photosensitizer and visible light. Such photomedical treatments have been known since the time of the ancient Egyptians but it was only just this year that this therapeutic modality was made available to modern medicine with the approval, in Canada, of Photofrin(R) for the treatment of bladder cancer. This paper reviews PDT with an emphasis on drug development, particulary for the second generation drugs, especially BPDMA (benzoporphyrin derivative-mono acid), which is now in human clinical trials.}, keywords = {BENZOPORPHYRIN DERIVATIVES, CELLS, HEMATOPORPHYRIN, INACTIVATION, MICE, PHOTOSENSITIZATION, PLASMA-LIPOPROTEINS, porphyrins, PROTEIN DAMAGE, PROTOPORPHYRIN}, isbn = {0008-4042}, url = {://A1994NN83000001}, author = {Dolphin, D.} } @inbook {2975, title = {USE OF POLYACRYLAMIDE-DERIVATIZED ANTIBODY IN DEXTRAN POLY(ETHYLENE GLYCOL) SYSTEMS}, booktitle = {Aqueous Two-Phase Systems}, series = {Methods in Enzymology}, volume = {228}, year = {1994}, note = {ISI Document Delivery No.: BA88LTimes Cited: 3Cited Reference Count: 15Review525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495}, pages = {390-395}, publisher = {Academic Press Inc}, organization = {Academic Press Inc}, address = {San Diego}, keywords = {CELLS, LIGAND, PARTITION, POLYMER 2-PHASE SYSTEMS}, isbn = {0076-6879}, url = {://A1994BA88L00036}, author = {Brooks, D. E. and Stocks, S. J.} } @article {2768, title = {THE EFFECT OF ARSENICALS ON ALKALOID PRODUCTION BY CELL-SUSPENSION CULTURES OF CATHARANTHUS-ROSEUS}, journal = {Applied Organometallic Chemistry}, volume = {7}, number = {7}, year = {1993}, note = {ISI Document Delivery No.: MQ500Times Cited: 1Cited Reference Count: 24}, month = {Nov}, pages = {477-486}, type = {Article}, abstract = {The effect of arsenic compounds on indole alkaloid production by cell suspension cultures of Catharanthus roseus was investigated. The analysis of indole alkaloids was achieved by using thermospray liquid chromatography-mass spectrometry (LC MS) which facilitated the rapid screening of alkaloid composition in cultures treated with different arsenicals at different times in their growth cycle. Treatment with dimethylarsinate (DMA), a non-selective herbicide, has a drastic inhibitory effect on alkaloid production although it is the least toxic arsenical to growth. Tryptamine, an early precursor in the biosynthesis of indole alkaloids, accumulates in cells treated with DMA, indicating that the initial step of condensation of tryptamine with secologanin is inhibited. Treatment with DMA during the early stationary phase of culture growth enhances the accumulation of some alkaloids, although some, such as catharanthine, are suppressed. The arsenicals arsenate and methylarsonate (MMA) have an inhibitory effect on alkaloid production when applied during the early growth stages. In contrast to MMA and DMA, arsenate has a stimulatory effect on catharanthine production when introduced to the culture during its early stationary phase. Thus the changes in the pattern of alkaloid accumulation on addition of arsenicals are dependent on the arsenic species and its concentration, as well as the time of application. This variable response indicates that each arsenical has a distinct mode of action on the secondary metabolic pathways of C. roseus.}, keywords = {ALKALOID PRODUCTION, ARSENIC COMPOUNDS, CELLS, THERMOSPRAY LC MS}, isbn = {0268-2605}, url = {://A1993MQ50000005}, author = {Cullen, W. R. and Hettipathirana, D. I.} } @article {7365, title = {INVITRO SCREENING OF CRUDE EXTRACTS AND PURE METABOLITES OBTAINED FROM MARINE-INVERTEBRATES FOR THE TREATMENT OF BREAST-CANCER}, journal = {Cancer Chemotherapy and Pharmacology}, volume = {30}, number = {5}, year = {1992}, note = {ISI Document Delivery No.: JG989Times Cited: 31Cited Reference Count: 27}, month = {Sep}, pages = {401-406}, type = {Article}, abstract = {A total of 15 samples (crude extracts and pure secondary metabolites) obtained from marine invertebrates collected from the offshore waters of British Columbia, Papua New Guinea, and Sri Lanka have previously been shown to exert cytotoxic activity in the in vitro L1210 leukemic bioassay. We screened these metabolites for in vitro cytotoxic activity against the drug-sensitive breast-tumor cell lines MCF-7, T-47D, ZR-75- 1, and MDA-MB23 1; the multidrug-resistant and P-glycoprotein (Pgp)-positive breast-tumor cell lines MCF-7 Ad(r) and MDA-Al(r); and normal and malignant human breast epithelial cells (HBEC) in primary culture. Eight samples exhibited significant [drug concentration resulting in a 50\% decrease in cell growth as compared with controls (ED50), <25-mu-g/ml] dose-dependent cytotoxicity against the drug-sensitive cell lines; the ED50 values were as low as 0.004-mu-g/ml. Five of the eight samples exhibited significant cytotoxicity against the multidrug-resistant cell lines; the ED50 values were as low as 0.0006-mu-g/ml. Incubation of MCF-7 Ad(r) cells with varying concentrations of compounds in the presence of Adriamycin demonstrated that none of the compounds tested interfered with Pgp function. Results obtained using HBEC in primary culture showed a wide range of chemosensitivities for a given drug against tissue taken from different patients, demonstrating the uniqueness of the response of different individuals to chemotherapy.}, keywords = {BREAST CANCER, CELLS, chemotherapy, COLORIMETRIC ASSAY, GROWTH, INVITRO SCREENING, MARINE ORGANISMS, SPONGE, TUMOR}, isbn = {0344-5704}, url = {://A1992JG98900011}, author = {Stingl, J. and Andersen, R. J. and Emerman, J. T.} }