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  • 1
    Electronic Resource
    Electronic Resource
    Use of recombinant poxviruses to stimulate anti-melanoma T cell reactivity (1998)
    Springer
    Annals of surgical oncology 5 (1998), S. 64-76 
    Details
    ISSN: 1534-4681
    Keywords: Melanoma ; Dendritic cells ; Melanoma-associated antigens ; MART-1 ; Recombinant viral vectors ; Poxviruses ; CTL
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Dendritic cells (DC) are potent professional antigen-presenting cells that can activate naive T lymphocytes and initiate cellular immune responses. As adjuvants, DC may be useful for enhancing immunogenicity and mediating tumor regression. Endogenous expression of antigen by DC could offer the potential advantage of allowing prolonged constitutive presentation of endogenously processed epitopes and exploitation of multiple restriction elements for the presentation of the same antigen. Methods: DC were prepared from the peripheral blood of HLA A*0201 patients with metastatic melanoma in the presence of IL-4 (1000 IU/mL) and GMCSF (1000 IU/mL). Recombinant vaccinia and fowlpox viruses encoding the hMART-1 gene were constructed and used to infect DC. The efficiency of infection and expression of the MART-1 antigen were assessed by immunohistochemistry and intracellular FACS analyses. Cytotoxic lymphocytes (CTL) were generated by the stimulation of CD8+ T cells, with DC expressing the recombinant gene. Reactivity of the CTL was determined at weeks 1 and 2 by the amount of IFN-γ released. Results: DC were infected with recombinant poxviruses and demonstrated specific melanoma antigen expression by immunohistochemistry, immunofluorescence, and intracellular FACS analysis. The expression by DC of MART-1 MAA after viral infection was sufficient to generate CD8+ T lymphocytes that recognized naturally processed epitopes on tumor cells in 10 of 11 patients. Conclusions: Human DC are receptive to infection by recombinant poxviruses encoding MAA genes and are capable of efficiently processing and presenting these MAA to cytotoxic T cells. The potential advantage of this approach is the ability to present specific antigen independent of the identification of the epitope or the MHC restriction element. This strategy may be useful for the identification of relevant epitopes for a diverse number of HLA alleles and for active immunization in patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02303766
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  • 2
    Electronic Resource
    Electronic Resource
    Histopathological analysis of metastatic melanoma deposits in patients receiving adoptive immunotherapy with tumor-infiltrating lymphocytes (1994)
    Springer
    Cancer immunology immunotherapy 38 (1994), S. 299-303 
    Details
    ISSN: 1432-0851
    Keywords: TIL ; Melanoma ; Histopathology ; Imaging ; Lymphocytic infiltrate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Tumor-infiltrating lymphocytes (TIL) from a wide range of human and murine tumors can be expanded in vitro using interleukin-2 (IL-2). These TIL are cytolytic T lymphocytes with in vivo and in vitro antitumor activity in mice and in humans. TIL from human melanoma can recognize autologous tumor in an MHC-restricted fashion, localize in vivo after111In labeling, and mediate regression of large metastatic deposits. Although studied extensively in vitro, less is known in vivo about TIL activity associated with tumor regression. This study was undertaken, in association with a study of TIL localization, to investigate mechanisms of TIL action by evaluating histopathological changes that occur at the tumor site during TIL administration. A total of 106 pre- and post-treatment pathological specimens from 25 patients enrolled in phase II TIL treatment and111In-TIL imaging protocols were examined blindly by a single pathologist. Histological subtype, lymphocytic infiltration, melanin content, vascularity, and necrosis were documented for each tumor specimen. Average baseline and post-treatment parameters were compared. Any significant changes were evaluated for correlation with clinical response and111In-TIL localization to tumor. Melanin content and vascularity of the tumor did not change as a result of therapy or correlate with either response or TIL localization. However, both increased lymphocytic infiltration and tumor necrosis were present after TIL administration (P=0.044 and 0.032 respectively). Furthermore, increases in lymphocytic infiltration correlated with tumor imaging using111In-TIL, and with the percentage of111In-labeled injectate present per gram of tumor specimen (P=0.036 and 0.0041 respectively). This suggests that TIL either account for the increased lymphocytes directly, or localize to tumor and recruit endogenous lymphocytes. We were unable to demonstrate any pretreatment histopathological predictors of response or variables that significantly correlated with subsequent clinical response, although peak and average values of necrosis were higher in responding patients compared to non-responding patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01525507
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  • 3
    Electronic Resource
    Electronic Resource
    Recognition of neuroectodermal tumors by melanoma-specific cytotoxic T lymphocytes: evidence for antigen sharing by tumors derived from the neural crest (1994)
    Springer
    Cancer immunology immunotherapy 39 (1994), S. 73-83 
    Details
    ISSN: 1432-0851
    Keywords: Melanoma ; Neural crest ; Ewing's sarcoma ; Tumor-infiltrating lymphocyte
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Melanomas from different patients have been shown to express shared tumor antigens, which can be recognized in the context of the appropriate MHC class 1 molecules by cytolytic T cells. To determine if T-cell-defined melanoma antigens are expressed on other tumors of neuroectodermal origin, four melanoma-specific cytotoxic T lymphocyte (CTL) cultures derived from tumor-infiltrating lymphocytes (TIL) were tested for lysis of a panel of 23 HLA-A2+ neuroectodermal tumor cell lines of various histologies, including retinoblastoma (1), neuroblastoma (8), neuroepithelioma (6), astrocytoma (2), neuroglioma (1), and Ewing's sarcoma (5). Low expression of MHC class I and/or ICAM-1 molecules was found on 22 of 23 neuroectodermal tumor lines, and could be enhanced by treatment with interferon γ (IFNγ). Following IFNγ treatment, three Ewing's sarcoma lines were lysed by at least one melanoma TIL culture, and levels of lysis were comparable to melanoma lysis by these TIL. Lysis could be inhibited by monoclonal antibodies directed against MHC class I molecules and against CD3, indicating specific immune recognition of tumor-associated antigens. None of the other neuroectodermal tumors tested were lysed by TIL, but they could be lysed by non-MHC-restricted lymphokine-activated killer cells. This demonstration of immunological cross-reactivity between melanomas and Ewing's sarcomas, two tumors of distinct histological types with a common embryonic origin, has implications for the developmental nature of these CTL-defined tumor antigens. It also raises the possibility that specific antitumor immunotherapies, such as vaccines, may be reactive against more than one form of cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01525312
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  • 4
    Electronic Resource
    Electronic Resource
    Generation of specific anti-melanoma reactivity by stimulation of human tumor-infiltrating lymphocytes with MAGE-1 synthetic peptide (1994)
    Springer
    Cancer immunology immunotherapy 39 (1994), S. 105-116 
    Details
    ISSN: 1432-0851
    Keywords: Melanoma ; MAGE-1 ; Tumor-infiltrating lymphocytes ; Immunotherapy ; Peptide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The MAGE-1 gene encodes a tumor-specific antigen, MZ2-E, which is recognized by cloned, specific cytolytic T cells (CTL) derived from the peripheral blood of a patient with melanoma. We have produced a MAGE-1-specific CTL line derived from the tumor-infiltrating lymphocytes (TIL) of a melanoma patient by weekly restimulation with autologous EBV-B cells pulsed with the synthetic HLA-A1-restricted MAGE-1 epitope nonapeptide EADPTGHSY. The 1277. A TIL line grew in long-term culture in low-dose interleukin-2 (IL-2) and IL-4, and exhibited antigen-specific, MHC-class-I-restricted lysis of HLA-A1-bearing MAGE-1+ cell lines. Cytolysis of target cells pulsed with the synthetic MAGE-1 decapeptide KEADPTGHSY was superior to that of cells pulsed with the immunodominant nonapeptide. Single amino-acid or even side-chain substitutions in the immunodominant nonamer abrogated cytolysis. 1277. A TIL specifically secreted tumor necrosis factor α after co-incubation with HLA-A1-expressing MAGE-1+ cell lines or fresh tumor. These data suggest that tumor-antigen-specific, MHC-restricted CTL may be grown from TIL in the presence of synthetic epitope peptides and expanded for adoptive immunotherapy in melanoma patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01525316
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  • 5
    Electronic Resource
    Electronic Resource
    Bandwidth and pebbling (1983)
    Springer
    Computing 31 (1983), S. 115-139 
    Details
    ISSN: 1436-5057
    Keywords: 05C99 ; 68E10 ; 94C15 ; Bandwidth ; graph pebbling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science
    Description / Table of Contents: Zusammenfassung Die Hauptergebnisse dieser Arbeit ergeben Beziehungen zwischen der „Bandwidth” eines GraphenG — die das Minimum ist, über alle Projektionen vonG auf eine Linie, von dem maximalen Abstand zwischen Bildern benachbarter Knoten vonG — und der Leichtigkeit, verschiedene „Pebble Games” aufG zu spielen. Es werden drei Pebble Games auf Graphen betrachtet: das wohlbekannte „computational” Pebble Game, die „progressive” (d. h. keine Wiederberechnung erlaubt) Version des computational Pebble Game, von denen beide auf directed acyclic Graphen gespielt werden, und das ziemlich verschiedene „breadth-first” Pebble Game, das auf undirected Graphen gespielt wird. Wir betrachten zwei verschiedene Kosten für das Pebble Game: die minimale Anzahl von Pebbles, die man braucht, um das Pebble Game auf einem GraphenG zu spielen, und die maximaleLebensdauer eines Pebble in einem Spiel, d. h. die maximale Anzahl von Zügen während denen ein Pebble auf dem Graphen verweilt. Die erste Gruppe von Hauptergebnissen in dieser Arbeit zeigt, daß die minimalen Lebensdauer-Kosten eines Spielverlaufs in einem der beiden letzten Pebble Games auf einem Graphen genau die Bandwidth vonG ist. Die zweite Gruppe von Ergebnissen stellt obere Schranken auf für die Anzahl von benötigten Pebbles in Abhängigkeit von der Bandwidth des betrachteten Graphen, z. B. um einen GraphenG mit Bandwidthk zu pebblen, braucht man höchstens min (2k 2+k+1, 2klog2|G|) Pebbles; ferner gibt es GraphenG von Bandwidthk für die man 3k−1 Pebbles braucht. Die dritte Gruppe von Ergebnissen setzt die Schwierigkeit, die Kosten eines Pebble Game auf einem gegebenen input-GraphenG festzustellen, in Beziehung zur Bandwidth vonG, z.B. das „Pebble Demand Problem” für Graphen mitn vertices von Bandwidthf(n) ist in der Klasse NSPACE (f(n)log2 n); und das „Optimal Lifetime Problem” ist für jedes der beiden letzten Pebble Games NP-vollständig.
    Notes: Abstract The main results of this paper establish relationships between the bandwidth of a graphG — which is the minimum over all layouts ofG in a line of the maximum distance between images of adjacent vertices ofG — and the ease of playing various pebble games onG. Three pebble games on graphs are considered: the well-known computational pebble game, the “progressive” (i.e., no recomputation allowed) version of the computational pebble game, both of which are played on directed acyclic graphs, and the quite different “breadth-first” pebble game, that is played on undirected graphs. We consider two costs of a play of a pebble game: the minimum number of pebbles needed to play the game on the graphG, and the maximumlifetime of any pebble in the game, i.e., the maximum number of moves that any pebble spends on the graph. The first set of results of the paper prove that the minimum lifetime cost of a play of either of the second two pebble games on a graphG is precisely the bandwidth ofG. The second set of results establish bounds on the pebble demand of all three pebble games in terms of the bandwidth of the graph being pebbled; for instance, the number of pebbles needed to pebble a graphG of bandwidthk is at most min (2k 2+k+1, 2k log2|G|); and, in addition, there are bandwidth-k graphs that require 3k−1 pebbles. The third set of results relate the difficulty of deciding the cost of playing a pebble game on a given input graphG to the bandwidth ofG; for instance, the Pebble Demand problem forn-vertex graphs of bandwidthf(n) is in the class NSPACE (f(n) log2 n); and the Optimal Lifetime Problem for either of the second two pebble games is NP-complete.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02259908
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  • 6
    Electronic Resource
    Electronic Resource
    Singlet oxygenation of 1,2-poly(1,4-hexadiene)s (1979)
    New York : Wiley-Blackwell
    Journal of Polymer Science: Polymer Chemistry Edition 17 (1979), S. 3751-3757 
    Details
    ISSN: 0360-6376
    Keywords: Physics ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The microstructural changes that occur in cis and trans forms of 1,2-poly(1,4-hexadiene) during methylene blue-photosensitized oxidation were examined by infrared (IR) and 13C-NMR spec-troscopy. The singlet oxygenation of these polymers yielded the expected allylic hydroperoxides accompanied by double bond shifts to new vinyl and trans-vinylene double bonds. The photosensitized oxidation exhibited zero-order kinetics; the relative rates for the cis- and trans-1,2-poly(1,4-hexadiene)s were approximately 3.8:1.0.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/pol.1979.170171130
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  • 7
    Electronic Resource
    Electronic Resource
    Photorearrangements of hydrocarbon polymers with pendant double bondsPresented at the Division of Polymer Chemistry at the ACS/CSJ Chemical Congress, Honolulu, Hawaii, April 1979. (1980)
    New York : Wiley-Blackwell
    Journal of Polymer Science: Polymer Chemistry Edition 18 (1980), S. 2543-2560 
    Details
    ISSN: 0360-6376
    Keywords: Physics ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A study was made of the microstructural changes that occur in ultraviolet irradiation under vacuum of thin films of 1,2-poly(cis-1,4-hexadiene) (CHD), 1,2-poly(trans-1,4-hexadiene) (THD), 1,2-poly(trans-1,3-pentadiene) (TPD), equibinary (1,2,-1,4) polybutadiene (EB), and equibinary (3,4-1,4) polyisoprene (EI). These polymers - all containing pendant double bonds - undergo important photoinduced loss of unsaturation, presumably through cyclization of the double bonds, by analogy to the previously reported photocyclization of 1,2-polybutadiene (VB) and 3,4-polyisoprene (VI)films. For the equibinary polymers, which contain internal as well as external (or pendant) double bonds, the loss of unsaturation is considered to involve photocyclization of 1,2-1,4 and 1,2-1,2 dyads in EB and of 3,4-1,4 and 3,4-3,4 dyads in EI. Accompanying thecyclization process in CHD, THD, and TPD is a direct photochemical cis-trans isomerization of —CH=CH—double bonds analogous to that originally noted for 1,4-polybutadiene. The photorearrangements in the above polymers with pendant double bonds were compared to the corresponding thermally induced rearrangements reported previoulsy;for VB and VI, in particular, the thermal, photo-and radiation-induced cycli-zations were found to be very similar, possibly having a common nonradical, nonionic mechanism involving excited double bonds.
    Additional Material: 15 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/pol.1980.170180813
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  • 8
    Electronic Resource
    Electronic Resource
    Photoconductivity of poly(hexamethylene adipamide) (1980)
    New York : Wiley-Blackwell
    Journal of Polymer Science: Polymer Physics Edition 18 (1980), S. 523-527 
    Details
    ISSN: 0098-1273
    Keywords: Physics ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Photocurrents induced by pulsed ultraviolet light in polyhexamethylene adipamide (nylon-66) have been studied. Two transient photocurrents are observed for light wavelenghts shorter than 3000 Å;. The first one is weakly field and temperature dependent and has been ascribed to electron photoinjection. On the whole, the time dependence of the two photoresponses suggests the possible formation of a space charge in the material.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/pol.1980.180180311
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  • 9
    Electronic Resource
    Electronic Resource
    Thermal expansion of epoxy-resin/particle composites - a size effect (1980)
    New York : Wiley-Blackwell
    Journal of Polymer Science: Polymer Physics Edition 18 (1980), S. 217-226 
    Details
    ISSN: 0098-1273
    Keywords: Physics ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The thermal expansion of epoxy-resin (Epikote 828)/particle composites has been measured in the range 77 to 450 K. The fillers used were Cu spheres (seven sizes from 5 to 150 μm diameter) and glass ballotini spheres (three sizes from 3.5 to 200 μm diameter). The volume concentrations used were 0.3 and 0.5 for Cu and 0.3 for glass. The experiments show that the addition of filler raises the glass transition temperature Tg, especially for fine particles. Below the normal value of Tg the thermal expansion is independent of particle size while above Tg the expansion is considerably smaller for samples containing the smaller particles. The effect is more pronounced for Cu than for glass filler. In addition a rapid heating rate reduces the expansion for specimens containing smaller particles but it does not effect the expansion for those containing large particles. The results, which are discussed in the light of the work of other authors, suggest that the addition of particles increases Tg by changing the nature of the polymer not only immediately at the particle surface but also for a considerable distance into the polymer itself. This probably occurs because the epoxy bonds strongly to the particles and this inhibits segmental rotations of the polymer even at considerable distances from the particle surface.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/pol.1980.180180204
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  • 10
    Electronic Resource
    Electronic Resource
    Synthesis of carbonate-containing high temperature poly(arylene-siloxanylenes) (1982)
    New York : Wiley-Blackwell
    Journal of Polymer Science: Polymer Chemistry Edition 20 (1982), S. 1-13 
    Details
    ISSN: 0360-6376
    Keywords: Physics ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A method for the first synthesis of high molecular weight carbonate-containing siloxanylene polymers was successfully developed. The procedure covered the preparation and polymerization of pure carbonate-containing bis-silanols which included bis(4-hydroxydimethylsilylphenyl)-carbonate, bis[4-(1-hydroxy-1,1,3,3-tetramethyldisiloxanyl)-phenyl] carbonate, and their meta analogs. Because conventional siloxane polymerization methods, such as the heterocondensation of bis-silanols with diaminosilanes or homocondensation reactions catalyzed by alkali reagents, decomposed carbonate linkages, a new polymerization technique that involved the use of phosgene was used. The procedure was both facile and effective in the polymerization of other arylene bis-silanols.
    Additional Material: 1 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/pol.1982.170200101
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