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  • 1
    ISSN: 1432-1084
    Keywords: Key words: Computed tomography ; Therapeutic radiology ; Gene therapy ; p53
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. The objective of this study was to prove the principle of CT-guided gene therapy by intratumoral injection of a tumor suppressor gene as an alternative treatment approach of incurable non-small-cell lung cancer. In a prospective clinical phase I trial six patients with non-small-cell lung cancer and a mutation of the tumor suppressor gene p53 were treated by CT-guided intratumoral gene therapy. Ten milliliters of a vector solution (replication-defective adenovirus with complete wild-type p53 cDNA) were injected under CT guidance. In four cases the vector solution was completely applied to the tumor center, whereas in two cases 2 ml aliquots were injected into different tumor areas. For the procedure the scan room had been approved as a biosafety cabinet. Gene transfer was assessed by reverse transcription and polymerase chain reaction in biopsy specimens obtained under CT guidance 24–48 h after therapy. Potential therapeutic efficacy was evaluated on day 28 after treatment using spiral CT. The CT-guided gene therapy was easily performed in all six patients without intervention-related complications. Besides flu-like symptoms, no significant adverse effects of gene therapy were noted. Three of the four patients with central injection exhibited gene transfer in the posttreatment biopsy. Gene transfer could not be proven in the two patients with multiple 2 ml injections. After 28 days, four of the six patients showed stable disease at the treated tumor site, whereas other tumor manifestations progressed. Computed tomography-guided injections are an adequate and easy-to-perform procedure for intratumoral gene therapy.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    s.l. ; Stafa-Zurich, Switzerland
    Materials science forum Vol. 210-213 (May 1996), p. 581-588 
    ISSN: 1662-9752
    Source: Scientific.Net: Materials Science & Technology / Trans Tech Publications Archiv 1984-2008
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Bradford : Emerald
    Compel 18 (1999), S. 372-384 
    ISSN: 0332-1649
    Source: Emerald Fulltext Archive Database 1994-2005
    Topics: Electrical Engineering, Measurement and Control Technology , Mathematics
    Notes: This paper deals with the inverse scattering problem of reconstructing the material properties of perfectly conducting or dielectric cylindrical objects. The material properties are reconstructed from measured far-field scattering data provided by the Electromagnetics Technology Division, AFRL/SNH, 31 Grenier Street, Hanscom AFB, MA 01731-3010. The measured data have to be calibrated for use in our reconstruction algorithm. The inverse scattering problem formulated as unconstrained nonlinear optimization problem is numerically solved using an iterative scheme with a variable calibration factor which will be determined during the optimization process. Numerical examples show the successful application of the method to the measured data.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Cytotoxic T lymphocytes (CTL) have previously been isolated from peripheral blood of patients with renal cell carcinoma (RCC). The CD8-positive CTL line MZ1257-CTL-5 (CTL-5) has been shown to lyse autologous cultured RCC cells in an HLA-A2 restricted fashion. Allogeneic, HLA-A2-matched RCC and melanoma cell lines were also lysed by CTL-5, suggesting that melanoma and renal cancer share antigenic determinants. The aim of the study was to determine whether RCC and melanoma share peptide epitopes that are recognized by CTL-5 in the context of HLA-A2 molecules. Peptides were acid-eluted from various cell lines, separated by reversed phase high performance liquid chromatography (RP-HPLC), and assessed for their ability to reconstitute the CTL-5-defined epitope by pulsing the peptides on HLA-A2 positive antigen-processing mutant cell line CEM × 721.174.T2 (T2). Peptides eluted from allogeneic HLA-A2-matched RCC and melanoma cell lines exhibited the CTL-5-defined epitope in the same HPLC fractions as peptides derived from the autologous RCC line. Renal cancer and melanoma cells preincubated with interferon-γ (IFN-γ) resulted in an additional peak of reconstitution activity in both cell types. This second lytic peak was also observed when high amounts of autologous RCC cells were used for peptide preparation without IFN-γ pretreatment, indicating that IFN-γ increases the amount of MHC class I/peptide complexes per cell, rather than inducing a neo-epitope.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The expression of the major histocompatibility complex (MHC) class I antigens is suppressed in early post-implantation embryonic cells as well as in embryonal carcinoma (EC) cells, but could be upregulated by treatment with interferon (IFN)-γ or retinoic acid. In a number of human and murine tumours, defects in the expression of the different components of the MHC class I antigen processing machinery, such as the proteasomal subunits LMP-2 and LMP-7 and the peptide transporters TAP-1 and TAP-2, account for impaired MHC class I surface expression. Here, we analysed the constitutive and IFN-γ regulated mRNA and protein expression of the LMP, TAP and MHC class I molecules in the human EC line 577LM. In comparison to lymphoblastoid control cells, poor constitutive mRNA and protein expression of LMP-7, TAP-1, HLA class I, and β2-microglobulin, but not of TAP-2 and LMP-2, was detected in 577LM cells. The lack of MHC class I surface expression on 577LM cells could not be enhanced either by culturing cells at low temperature or by their incubation with exogenous MHC class I specific binding peptides: thus, the defective MHC class I surface expression was not only caused by impaired generation and processing of antigenic peptides. IFN-γ treatment of 577LM resulted in a significant increase of MHC class I surface expression which was preceded by an upregulation of TAP, LMP and MHC class I transcripts as well as of TAP-1 and TAP-2, but not of LMP-2 and LMP-7, protein expression. These data suggest that human EC cell lines show a stable expression of a MHC class I low/deficient phenotype. The deficiencies associated with this phenotype involve different levels of the MHC class I restricted antigen presentation machinery and could be modified by treatment with IFN-γ.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, U.K. and Cambridge, USA : Blackwell Science Ltd
    Scandinavian journal of immunology 43 (1996), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: A number of tumours and oncogene transformed cells displayed reduced MHC class I surface expression which seemed to enable their escape from immune surveillance. To test whether oncogenic activation is directly involved in suppressing MHC class I expression, a model of inducible oncogene expression was chosen. Mouse fibroblasts transfected with different oncogenes expressed under the control of the dexamethasone-inducible MMTV promoter were analysed in the presence and absence of hormone for the mRNA and protein expression of MHC class I molecules as well as the respective oncogenes. Immunofluorescence analyses demonstrated an inverse association of MHC class I and oncogene expression after dexamethasone stimulation, independent of the type of oncogene causing transformation. Hormone-mediated induction of oncogene expression caused down-regulation of all H-2 loci. Kinetic experiments using MMTV c-Ha-ras(A) transfectants revealed that down-regulation of MHC class I surface expression was preceded by a dexamethasone-induced change of morphology, anchorage-independent growth, and an increase of the ras protein p 21. Parallel monitoring of mRNA expression demonstrated a time-dependent up-regulation of ras specific transcripts, which was associated with differential regulation of MHC class I heavy and light chain transcripts. β2-microglobulin transcripts were transiently suppressed, whereas MHC class I heavy chain transcripts remained unaffected. To investigate the mechanisms of oncogene-mediated down-regulation of MHC class I expression, H-2 promoter transfections and a nuclear run on assays were performed. In MMTV c-Ha-ras(A) cells, neither alterations of the H-2 promoter activity nor of the transcriptional activity of H-2 antigens was observed in the presence of dexamethasone, whereas both could be up-regulated by interferon-γ treatment. These data suggest that oncogene-mediated transformation is directly associated with MHC class I down-regulation, but that complex interactions affecting MHC class I heavy and light chain genes at the transcriptional and/or post-transcriptional level are involved in this process.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Der Onkologe 4 (1998), S. 247-250 
    ISSN: 1433-0415
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Die Lebenserwartung des Patienten mit metastasiertem Nierenzellkarzinom (NZK) ist kurz, so liegt die 5-Jahresüberlebenszeit im Stadium IV mit Fernmetastasen unter 10% [5]. Dennoch existiert eine kleine Gruppe von Patienten, die durch günstigeren Spontanverlauf und lange Überlebenszeiten charakterisiert ist. Desweiteren kommt es beim NZK zu immer wieder beschriebenen Spontanremissionen [12], die jedoch in den wenigen einschlägigen Studien mehrheitlich unter 1% liegen. In der palliativen Behandlung des NZK wurden multiple Chemotherapeutika, deren Ergebnisse bzgl. Remissionsraten und Verlängerung der Überlebenszeit der Patienten jedoch durchgehend enttäuschend sind, eingesetzt. Das NZK ist ein weitgehend chemotherapiere- sistenter Tumor, bei dem unterschied- liche, in ihrem Stellenwert noch nicht eindeutig geklärte Resistenzmechanismen beschrieben werden. Die folgende Übersicht soll einen Überblick über Chemotherapiestudien in der Behandlung des metastasierten NZK geben und Mechanismen ihrer Chemotherapieresistenz und therapeutische Anstrengungen zur Durchbrechung zusammenfassen.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Fresenius' journal of analytical chemistry 359 (1997), S. 150-154 
    ISSN: 1432-1130
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A pH-optode is described based on 1, 3, 5, 7-tetramethyl-8-(4-dimethylamino)-4-difluorobora-3a, 4a-diaza-(s)-indacene (1) immobilized in a hydrogel matrix. Its uncharged form is non-fluorescent, whereas the protonated form displays strong emission. The quenching of the emission can be mechanistically explained by a PET (photoinduced electron transfer) from the dimethylamino group to the fluorophore. The perpendicular configuration at the C(8)-aryl bond contributes to the efficiency of the on/off-switching behavior. Incorporation of the dye into a hydrogel matrix results in a transparent sensor membrane which can be used to measure the pH in the range of 1-3. The sensor shows high signal intensity, good reproducibility, and the response characteristic is stable over hours of operation even at low pH-values.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1612-1112
    Keywords: Column liquid chromatography ; Electrospray ionization mass spectrometry ; Micropellicular poly-styrene/divinylbenzene ; Peptides and proteins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary Short columns packed with highly crosslinked 2.3 μm poly-styrene/divinylbenzene (PS/DVB) particles were used for rapid and efficient separation of proteins and peptides by reversed-phase high-performance liquid chromatography at elevated temperatures. Enhancement of the diffusivities of the sample components at elevated temperatures together with the short diffusion pathlength with the micropellicular polymeric stationary phases were responsible for high efficiency, high speed of analysis, and short column regeneration times. Underivatized PS/DVB beads as well as PS/DVB microspheres which have been modified with polyvinylalcohol or octadecyl chains on the surface were synthesized, employed, and compared to HY-TACH-C18, a commercially available micropellicular octadecyl-silica stationary phase, for the separation of proteins, octapeptides and tryptic protein digests. Highest performance was obtained with the silica- and PS/DVB-based octadecyl stationary phases, which exhibited similar column efficiencies but different selectivities for proteins and peptides. The minimum detectability at 214 nm and the maximum loading capacity for ribonuclease A using analytical 30×4.6 mm I.D. columns were 10 ng (0.6 pmol) and 1 μg, respectively. Finally, reversed-phase HPLC with a 60×2 mm I.D. narrow-bore column packed with micropellicular octadecyl PS/DVB was coupled successfully to electrospray mass spectrometry at a flow-rate of 0.15 mL min−1 and on-line full-scan mass spectra for molecular mass determination and identification of proteins in the lower picomol range were obtained.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1612-1112
    Keywords: Column liquid chromatography ; Polymeric bonded phase ; Anion-exchange chromatography ; Pulsed amperometric detection ; Carbohydrates
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary This paper reports the results of a study on the use of a new polymer-based, strong anion-exchange, stationary phase for rapid and selective separation of carbohydrates and related compounds by high-pH, anion-exchange chromatography with pulsed amperometric detection. The new adsorbent has been obtained by direct nitration of 2.8 μm, spherical non-porous highly crosslinked, styrene-divinylbenzene copolymer beads, followed by reduction of superficially introduced nitro groups with nascent hydrogen and quaternization of the resultant amino groups with iodomethane. It is reported that by optimizing the ionic strength of the mobile phase, columns packed with the new anion-exchanger can be successfully employed to separate, either in isocratic or gradient elution mode, oligosaccharides, positional isomers of gluco-disaccharides, as well as uronic acids and sugar monophosphates.
    Type of Medium: Electronic Resource
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