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  • 1995-1999  (53)
  • 1900-1904  (1)
  • Chemistry  (44)
  • Pharmacokinetics  (4)
  • Arabidopsis  (3)
  • Tyr(P)-containing peptides  (3)
Material
Years
Year
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Cancer chemotherapy and pharmacology 36 (1995), S. 115-120 
    ISSN: 1432-0843
    Keywords: Cholera toxin ; Immunoassay ; Pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cholera toxin was selected for pharmacologic evaluation by the National Cancer Institute on the basis of antiproliferative activity against small-cell and nonsmall-cell lung-cancer cell lines. A feature common to the sensitive cell lines was abundant expression of GM1 ganglioside, the cellular receptor for cholera toxin. A sandwich enzyme-linked immunosorbent assay (ELISA) was developed to quantitate cholera toxin in biological fluids. A sigmoidal relationship was observed between the cholera toxin plasma concentration and the absorbance at 490 nm (OD490) of the product of horseradish peroxidase-catalyzed oxidation ofo-phenylenediamine over the range of 6.25–1,600 ng/ml. Logit transformation of the OD490 data was linear over the entire concentration range and assay variability was less than 25%. Cholera toxin was stable in murine and human whole blood and plasma. Following i.v. administration of 1,500 μg/kg to male CD2F1 mice, cholera toxin plasma elimination was described by a two-compartment open model. The half-lives (t 1/2α,t 1/2β), plasma clearance, and steady-state volume of distribution were 0.7 min, 49 min, 24 ml min−1 kg−1 912 ml/kg, respectively. Cholera toxin was not detected in plasma following an s.c. dose of 1,500 μg/kg. Urinary recovery following intravenous drug administration was less than 0.1%.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Cancer chemotherapy and pharmacology 37 (1995), S. 39-46 
    ISSN: 1432-0843
    Keywords: Key words Cisplatin ; Interferon α ; Continuous infusion therapy ; Non-small cell lung cancer ; Pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Combination therapy of cisplatin with interferon α (IFN) has been shown in several in vitro as well as in vivo models to be synergistic. In order to decrease toxicity seen with cisplatin, 5-day continuous infusions, in place of bolus administration, have been introduced. This led us to investigate the combination of 5-day continuous infusion cisplatin with repeated IFN dosing in a phase I cisplatin dose escalation study. A group of 17 patients were enrolled in this trial . The maximum tolerated dose (MTD) of cisplatin was 20 mg/m2 per day when combined with 3×106 units IFN given three times a week. The dose-limiting toxicities seen included thrombocytopenia, leukopenia, and nausea and vomiting. Pharmacokinetic analyses of free (unbound or ultrafilterable) platinum revealed that the decay curve fitted a monoexponential model. Pharmacokinetic parameters of cisplatin were found to correlate with toxicity. Both increases in the maximum concentration of cisplatin achieved (Cpmax) as well as the area-under-the-curve (AUC) for free platinum, correlated with the incidence of nausea and vomiting (both acute and delayed) and hematological toxicities (leukopenia and thrombocytopenia). None of the patients exhibited significant changes in renal function while on this study. The free platinum levels were higher than found in similar studies evaluating comparable cisplatin infusions alone. The enhanced toxicities seen in this trial may be explained by the results of an in vitro study using human plasma spiked with cisplatin and IFN that revealed decreased protein binding of cisplatin by 2.5–3.0-fold. Of the 17 patients treated, two non-small cell lung cancer patients obtained a partial response and one malignant melanoma patient obtained complete resolution of a malignant pleural effusion. Considering the acceptable toxicity seen in this trial, we recommend phase II trials be conducted with continuous infusion cisplatin with IFN in the treatment of non-small cell lung cancer.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Cancer chemotherapy and pharmacology 36 (1995), S. 115-120 
    ISSN: 1432-0843
    Keywords: Key words Cholera toxin ; Immunoassay ; Pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cholera toxin was selected for pharmacologic evaluation by the National Caner Institute on the basis of antiproliferative activity against small-cell and non-small-cell lung-cancer cell lines. A feature common to the sensitive cell lines was abundant expression of GM1 ganglioside, the cellular receptor for cholera toxin. A sandwich enzyme-linked immunosorbent assay (ELISA) was developed to quantitate cholera toxin in biological fluids. A sigmoidal relationship was observed between the cholera toxin plasma concentration and the absorbance at 490 nm (OD490) of the product of horseradish peroxidase-catalyzed oxidation of o-phenylenediamine over the range of 6.25–1,600 ng/ml. Logit transformation of the OD490 data was linear over the entire concentration range and assay variability was less than 25%. Cholera toxin was stable in murine and human whole blood and plasma. Following i.v. administration of 1,500 μg/kg to male CD2F1 mice, cholera toxin plasma elimination was described by a two-compartment open model. The half-lives (t 1/2α, t 1/2β), plasma clearance, and steady-state volume of distribution were 0.7 min, 49 min, 24 ml min-1 kg-1 912 ml/kg, respectively. Cholera toxin was not detected in plasma following an s.c. dose of 1,500 μg/kg. Urinary recovery following intravenous drug administration was less than 0.1%.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0843
    Keywords: Key words Immunotoxins ; Gelonin ; Melanoma ; Recombinant toxins ; Pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Immunotoxins are a class of targeted therapeutic agents under development by various research groups. The murine monoclonal antibody designated ZME-018 recognizes a high molecular weight glycoprotein present on most human melanoma cells and biopsy specimens and has been utilized for clinical imaging studies in patients with melanoma. The plant toxin gelonin is a ribosome-inactivating protein (RIP) with n-glycosidase activity similar to that of ricin A chain. In previous studies by our group, the gelonin toxin was sequenced, cloned and expressed in E. coli. The purified recombinant gelonin (RG) was found to have identical protein synthesis inhibitory activity to that of natural gelonin (NG). For comparative purposes, chemical conjugates of antibody ZME and either RG or NG were produced using the heterobifunctional crosslinking reagents SPDP and SMPT. The ZME-NG and ZME-RG immunotoxins were found to be 104- to 105-fold more cytotoxic to antigen-positive human melanoma cells than free toxin. NG toxin alone was cytotoxic to intact cells (IC50 = 100 nM) while RG was nontoxic to cells at doses up to 1 μM. Both ZME-NG and ZME-RG immunoconjugates were nontoxic to antigen-negative (Me-180) cells. ZME-RG immunotoxins constructed with the more stable SMPT reagent were slightly more effective in culture than conjugates made with SPDP. Tissue distribution studies in tumor-bearing nude mice demonstrated that tumor uptake of the ZME-RG immunotoxin was similar to that of the intact ZME antibody with reduced distribution to normal organs compared to an immunoconjugate produced with NG. Pharmacokinetic studies showed that the terminal-phase plasma half-life of ZME-RG was similar to that of ZME itself (42 h vs 50 h) and almost threefold higher than that of ZME-NG (11.5 h). The area under the concentration curve (Cxt) for ZME-RG was 50% lower than that for ZME due to an increased apparent volume of distribution (Vda) but was almost tenfold higher than the Cxt for ZME-NG. These studies suggest that immunoconjugates comprising RG demonstrate identical in vitro cytotoxic effects to immunoconjugates produced with NG and immunotoxins with RG display improved in vivo pharmacodynamics and tissue distribution compared to immunotoxins containing NG.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1573-5028
    Keywords: Arabidopsis ; serine/threonine phosphatase ; PP2A ; B regulatory subunit
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Type 2A serine/threonine protein phosphatases (PP2A) are key components in the regulation of signal transduction and control of cell metabolism. The activity of these protein phosphatases is modulated by regulatory subunits. While PP2A activity has been characterized in plants, little is known about its regulation. We used the polymerase chain reaction to amplify a segment of a cDNA encoding the B regulatory subunit of PP2A from Arabidopsis. The amplified DNA fragment of 372 nucleotides was used as a probe to screen an Arabidopsis cDNA library and a full-length clone (AtBα) of 2.1 kbp was isolated. The predicted protein encoded by AtBα is 43 to 46% identical and 53 to 56% similar to its yeast and mammalian counterparts, and contains three unique regions of amino acid insertions not present in the animal B regulatory subunit. Genomic Southern blots indicate the Arabidopsis genome contains at least two genes encoding the B regulatory subunit. In addition, other plant species also contain DNA sequences homologous to the B regulatory subunit, indicating that regulation of PP2A activity by the 55 kDa B regulatory subunit is probably ubiquitous in plants. Northern blots indicate the AtBα mRNA accumulates in all Arabidopsis tissues examined, suggesting the protein product of the AtBα gene performs a basic housekeeping function in plant cells.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1573-5028
    Keywords: Arabidopsis ; PP2A regulatory subunit ; serine/threonine phosphatase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract We have indentified a novel gene (AtBβ) encoding a previously uncharacterized isoform of the B regulatory subunit of the type 2A serine/threonine protein phosphatase (PP2A) of Arabidopsis, and show that mRNA derived from the AtBβ gene accumulates in all Arabidopsis organs. In addition, we examined the expression of the three genes encoding the A regulatory subunit of Arabidopsis PP2A and show these genes are expressed in all organs as well. Taken together, our results suggest a myriad of PP2A subunit combinations, possibly with distinct substrate specificities, may occur within each Arabidopsis cell.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-2048
    Keywords: Arabidopsis ; Ferric chelate reductase ; Root hair ; Transfer cell
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Arabidopsis thaliana (L.) Heynh. Columbia wild type and a root hair-less mutant RM57 were grown on iron-containing and iron-deficient nutrient solutions. In both genotypes, ferric chelate reductase (FCR) of intact roots was induced upon iron deficiency and followed a Michaelis-Menten kinetic with a K m of 45 and 54 μM FeIII-EDTA and a V max of 42 and 33 nmol Fe2+·(g FW)−1·min−1 for the wild type and the mutant, respectively. The pH optimum for the reaction was around pH 5.5. The approximately four fold stimulation of FCR activity was independent of formation of root hairs and/or transfer cells induced by iron deficiency. Iron-deficiency-induced chlorosis and the development of a rigid root habit disappeared when ferric chelate was applied to the leaves, while FCR activity remained unchanged. The time course of the responses to iron deficiency showed that morphological and physiological responses were controlled separately.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The small-angle x-ray scattering (SAXS) technique has been applied to investigate solution and gel structures of alginate in the absence and presence of two divalent cations: Ca(II) and Cu(II). We have observed a broad maximum in the scattering curve, a characteristic of polyelectrolyte, for the purified alginate sample. The scattering maximum disappears in excess of added simple salt and shifts toward the higher angle region with increasing alginate concentration. Concentration dependence of the position and intensity of the maximum follows power law relations with exponents close to those predicted by theory. Data analysis shows an increase in correlation length ξ and cross-sectional diameter d0, of polymer chains upon gelation and suggests that a dimeric structure is adopted in the junction zone, consistent with the “egg-box” model previously proposed. In the Ca(II)-alginate system, the molecular parameters ξ and d0 are found to have good correlation with the macroscopic properties of gelation, such as gel point determined by viscosity measurements. However, for the Cu(II)-alginate system there is no clearly transitional behavior observed in ξ and d0, implying that the junction zone may be replaced by a more uniformly distributed site binding of Cu(II) ions to the carboxyl groups of both mannuronate and guluronate residues, in confirmation of previous 13C-nmr results. © 1995 John Wiley & Sons, Inc.
    Additional Material: 14 Ill.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 78 (1995), S. 1215-1218 
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The thermal properties of two ferrocene derivatives, substituted by either one or two cholesteryloxycarbonyl units, were investigated. While the monosubstituted ferrocene derivative 1 was found to be non-mesomorphic, the disubstituted ferrocene derivative 2 exhibited a crystal smectic-B phase. This result shows that ferrocene-containing thermotropic liquid crystals, despite the bulkiness of the metallocene core, are not limited to disordered calamitic phases.
    Additional Material: 1 Ill.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Berichte der deutschen chemischen Gesellschaft 129 (1996), S. 521-525 
    ISSN: 0009-2940
    Keywords: Liquid crystals ; Siloxanes ; Phase behaviors ; Defined topology ; Chemistry ; Inorganic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: It is shown that supermolecules with a tetrahedral symmetry and appropriate side-chains exhibit liquid-crystalline phase behaviour. The use of an optimised hydrosylation reaction allows for the synthesis of materials that have four mesogenic groups attached to a siloxane core, where the conformation and the configuration are unambiguous. The materials show low glass transition temperatures and, depending on the spacer length, complex liquid-crystalline morphologies.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
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