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  • 1
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Immunological reviews 6 (1971), S. 0 
    ISSN: 1600-065X
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Immunological reviews 136 (1993), S. 0 
    ISSN: 1600-065X
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    ISSN: 1436-2813
    Schlagwort(e): the role of spleen ; tumor-bearer ; splenectomy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Morphologic changes of the spleen and dynamic changes of biologic activity of spleen cells from C3H/HeJ mice bearing methylcholanthrene induced fibrosarcoma (MCA-F) were investigated in different stages of tumor growth, using local adoptive transfer assay (LATA). The spleen size, weight and the number of spleen cells increased with the tumor growth. In early and late stages of tumor growth, tumor-bearing mice possessed non-specific tumor-enhancing cells which were radioresistant (700 rads), phagocytic and adherent, suggesting that they were macrophages. On the other hand, in middle stages of tumorgenesis, tumor-bearing mice possessed specific cytotosic cells which were radiosensitive (700 rads) and anti-Thy 1.2 serum positive, suggesting that they were T-cells. Thus, the appearance of tumor-enhancing cells was earlier than cytotoxic cells in MCA-F bearing host, and the balance of tumor-enhancing and cytotoxic cells may influence the tumor outgrowth in different stages of tumorgenesis. The spleen serves as a reservoir of factors which either abrogate cell mediated resistance or stimulate neoplastic growth, or as the source of cytotoxic cells, at certain times of tumor burden.
    Materialart: Digitale Medien
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  • 4
    ISSN: 1436-2813
    Schlagwort(e): the role of spleen ; tumor-bearer ; splenectomy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The effect of splenectomy on neoplastic outgrowth was examined prior to and after implantation of methylcholanthrene-induced C3H/He murine tumors. Splenectomy performed 12 days before tumor inoculation did not affect the tumor outgrowth, however, both splenectomy and sham operation performed shortly before tumor inoculation resulted in significant tumor facilitation compared with the non-operated group, suggesting that this accelerated tumor was not related to the presence or absence of splenic tissue, but rather to systemically-induced immunosuppression. While splenectomy performed 6, 9, 12 days after tumor inoculation did not alter the tumor growth, splenectomy performed early (3 days) or late stage (20 days) after tumor cell challenge revealed a retarded neoplastic outgrowth, compared with the sham operated group. These results suggest that splenectomy in very early and late stages of tumor-bearing host may be effective for tumor treatment.
    Materialart: Digitale Medien
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  • 5
    Digitale Medien
    Digitale Medien
    Springer
    Cancer immunology immunotherapy 19 (1985), S. 22-27 
    ISSN: 1432-0851
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Immunization with the tumor-specific transplantation antigens (TSTA) of experimental, chemically induced sarcomas engenders specific host resistance to challenge with viable, homotypic neoplastic cells. The strength of tumor resistance depends upon the physical state of the TSTA used for immunization. Treatment with 105–106 irradiated tumor cells, a 2-log dose range, induces complete rejection of neoplastic challenges, while immunization within a 1-log dose range with crude 3 M KCl or with 2.5% butanol extracts containing TSTA evokes a weak state of resistance characterized by decreased outgrowth of tumor challenges, but not neoplastic regression. The reduced immunogenicity may be due to either contamination with substances that antagonize host resistance, for example by induction of suppressor cells, or an intrinsic limitation by virtue of the molecular properties of extracted compared with cell-surface TSTA. MCA-F and MCA-D, two noncross-reactive fibrosarcomas induced in C3H/HeJ mice with 3-methylcholanthrene, were employed to compare the relative immunogenic activity of intact tumor cells, 2.5% butanol extracts, and materials sequentially purified by preparative isoelectric focusing (pIEF), preparative isotachophoresis (pITP), and high performance gel permeation chromatography (HPGPC). Immunoprotective TSTA activity purified 50,000-fold by this protocol extended the effective dose range by four to five logs: 15 pg to 1.5 μg MCA-F or 1 pg to 10 ng MCA-D antigen-induced specific host resistance. However, despite the appreciable purification of TSTA, immunization with extracted materials only delayed neoplastic outgrowth. They induced neither immediate rejection nor only temporary progression of transplanted tumor cells. Thus, purified TSTA preparations by themselves lack the immunogenic properties of intact cells that result in maximal induction of tumor resistance.
    Materialart: Digitale Medien
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  • 6
    Digitale Medien
    Digitale Medien
    Springer
    Transplant international 9 (1996), S. 527-534 
    ISSN: 1432-2277
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Conclusion Advances in the practice of transplantation are integrally related to developments in the field of immunosuppression. During the first 70 years of investigation, radiation and cytotoxic and cytostatic chemicals were used to produce nonselective immunosuppression. The greatest advance during the past decade was the development of the immunoregulatory, T-cell-selective agents CyA, OKT3, TRL, and SRL. However, when used individually, these agents have narrow therapeutic windows. In the 1990s, the administration of combinations of subtherapeutic doses of CyA and SRL, drugs that act both selectively and synergistically, has reduced the incidence of acute rejection episodes substantially and mitigated the need for chronic corticosteroid therapy. However, because the CyA/SRL combination shows potentially overlapping toxicity profiles, pharmacokinetic interactions, and limited immunological activity in rigorous rejection models, further research may be required to discover regimens that more effectively exploit the immunosuppressive strategy of synergism. During the next millennium, the primary goal of research in immunosuppression must be the development of a method to induce specific immunological tolerance of clonotypic lymphoid cells directed against foreign donor epitopes without affecting the rest of the immune repertoire. Thus, just as 3000 years ago the actions of the three Fates established the rationale by which people conducted their lives, the coalescence of three effects — selectivity, synergy, and specificity — will undoubtedly be the basis of the immunosuppressive regimen of the future.
    Materialart: Digitale Medien
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  • 7
    Digitale Medien
    Digitale Medien
    Springer
    World journal of surgery 10 (1986), S. 348-360 
    ISSN: 1432-2323
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Résumé La cyclosporin (CsA) a amélioré l'avenir de l'allotransplantation. En raison d'une action relativement élective sur les lymphocytes T elle provoque moins de complications immunosuppressives, infectieuses ou néoplasiques, que les agents chimiques employés jusqu'alors, agents dont le spectre d'action était relativement non spécifique sur les cellules lymphoïdes. Les troubles gastrointestinaux secondaires à l'ingestion et les réactions vaso-motrices secondaires à l'injection intraveineuse de la CsA représentent une toxicité pharmacologique rarement importante. Les complications inhérentes à la toxicité du produit intéressent au premier chef le système neuro-ectodermique et aussi le mésenchyme hépatique et le mésenchyme rénal. Alors que les complications du premier groupe sont rarement graves la néphrotoxicité rénale indiscutable de la CsA impose des limites à son emploi. Si la réduction de la fonction rénale est de l'ordre de 33% quand la drogue est employée pour traiter les maladies auto-immunes, le phénomène étant réversible dès l'arrêt de l'emploi de la drogue, un dysfonctionnement rénal grave se manifeste chez le transplanté en particulier lorsque d'autres agents médicamenteux néphrotoxiques sont employés simultanément. Au niveau du rein greffé de nombreux facteurs amplifient la lésion provoquée par la CsA: réactions adverses acquises du donneur, accumulation prolongée du produit au niveau du transplant et réjection de ce dernier. Du au fait que les manifestations cliniques et histologiques de la néphrotoxicité de la CsA ont tendance à être polymorphes aucune stratégie diagnostique et thérapeutique n'a pu être définie. Des faits, résultant de l'étude pharmacologique au cours du traitement, suggèrent que les sujets candidats à la néphrotoxicité peuvent être identifiés en fonction de plusieurs données: taux élevés de la drogue dans le sérum, élargissement de l'aire située au-dessous de la courbe de concentration du taux plasmatique, prolongation de la demi-vie d'élimination, élévation de la sensibilitié pharmacodynamique à la CsA. L'analyse des données pharmacologiques et des données cliniques devrait fournir des protocoles thérapeutiques efficaces et dénués de risques importants de complications.
    Kurzfassung: Resumen La terapia con ciclosporina (CsA) ha mejorado el resultado de los alotransplantes. En virtud de una acción relativamente selectiva sobre los linfocitos T, la terapia con CsA causa menos complicaciones inmunosupresivas de tipo infeccioso o de neoplasia maligna en comparación con otros agentes químicos previos que son relativamente inespecíficos en cuanto a su espectro de acción sobre células linfoides versus las células no linfoides. Las alteraciones gastrointestinales consecuentes a la administración oral y las reacciones vasomotoras consecuentes a la administración intravenosa representan toxicidad farmacológica que rara vez es de importancia clínica mayor. Las complicaciones que induce esta droga afectan primordialmente a los sistemas neuroectodérmico y mesenquimatosos hepáticos y renales. En tanto que aquel grupo de complicaciones raramente reviste gravedad, la nefrotoxicidad mesenquimatosa plantea una limitación mayor al uso de esta terapia. Por una parte, reducciones del 33% en la función renal normal en pacientes tratados con CsA por enfermedad autoinmune aparecen reversibles al descontinuar la terapia. Por otra parte, severa disfunción renal ocurre en pacientes transplantados, especialmente en presencia de terapia concomitante con drogas nefrotóxicas. Dentro del contexto del transplante renal numerosos factores incrementan la lesión inducida por la droga, incluyendo condiciones adversas en la obtencion del órgano donante, almacenamiento prolongado del transplante y rechazo del aloinjerto. Puesto que los hallazgos clínicos e histológicos en la nefrotoxicidad por CsA tienden a ser pleomórficos, no ha surgido una estrategia diagnóstica o terapéutica única. Sin embargo, la experiencia ganada de la monitoría farmacológica de los recipientes de aloinjertos renales sugiere que el grupo con mayor riesgo de nefrotoxicidad puede ser identificado mediante la determinación de los niveles séricos de la droga, el aumento del área bajo la curva del tiempo de concentración plasmática, la prolongación del tiempo medio de eliminación y la aumentada sensibilidad farmacodinámica a la CsA. El análisis de los datos farmacológicos junto con los resultados clínicos habrá de sugerir regímenes terapéuticos de máxima efectividad con mínimo riesgo de complicaciones.
    Notizen: Abstract Cyclosporin (CsA) therapy has improved the outcome of allotransplants. Because of a relatively selective action on T lymphocytes, CsA therapy causes fewer immunosuppressive complications of infection or malignancy compared to previous chemical agents, which were relatively nonspecific in their spectrum of action on lymphoid versus nonlymphoid cells. Gastrointestinal complaints after oral administration and vasomotor reactions after intravenous administration represent pharmacologic toxicities rarely of major clinical import. Drug-induced complications involve primarily the neuroectodermal, or the mesenchymal hepatic and renal, systems. While the former group of complications are rarely severe, mesenchymal nephrotoxicity poses a major limitation of drug therapy. On the one hand, reductions by 33% of normal renal function in patients treated with CsA for autoimmune disease appear to be reversible on discontinuance of therapy. On the other hand, severe renal dysfunction occurs in transplant recipients, particularly in the presence of concomitant therapy with nephrotoxic drugs. In the kidney transplant setting, numerous factors exacerbate the druginduced injury, including adverse donor procurement conditions, prolonged graft storage, and allograft rejection. Since the clinical and histologic findings in CsA nephrotoxicity tend to be pleiomorphic, no single diagnostic or therapeutic strategy has emerged. However, insights gained through pharmacologic monitoring of renal allograft recipients suggest that the group at increased risk for nephrotoxicity can be identified by elevated serum drug trough levels, increased area under the plasma time concentration curve, prolonged elimination half-life, and heightened pharmacodynamic sensitivity to CsA. Analysis of pharmacologic data in conjunction with clinical results should provide drug regimens of maximal therapeutic index with minimal risk of complications.
    Materialart: Digitale Medien
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  • 8
    Digitale Medien
    Digitale Medien
    Springer
    Cancer immunology immunotherapy 13 (1982), S. 48-52 
    ISSN: 1432-0851
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Rabbits imunized with the immunoprotective TSTA fraction partially purified by preparative isoelectric focusing of 3 M KCl extracts from a chemically induced murine sarcoma, MCA-F, produced specific xenoantisera as assessed by an indirect membrane immunofluorescence assay. Only the immunizing tumor, MCA-F, and not the antigenically distinct MCA-D or MCA-T target cells were stained by the xenoantiserum. Absorption of anti-MCA-F antiserum with the antigenically distinct MCA-D or MCA-T cells did not reduce its capacity to bind to MCA-F cells. The immunofluorescence reaction was competitively inhibited by MCA-F fractions that induced specific immunoprotection: crude 3 M KCl extract, isoelectrically focused TSTA (fraction 15), and intact irradiated MCA-F cells. The TSTA specificity of these xenoantisera suggests that they may provide useful reagents for rapid isolation and characterization of the immunoprotective moiety.
    Materialart: Digitale Medien
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  • 9
    Digitale Medien
    Digitale Medien
    Springer
    Cancer immunology immunotherapy 16 (1983), S. 101-108 
    ISSN: 1432-0851
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Tumor-specific transplantation antigens (TSTA) were purified from 3 M KCl and butanol extracts of C3H/HeJ 3-methylcholanthrene-induced fibrosarcomas by preparative isotachophoresis (pITP). Fractions from pITP which reacted with antisera to TSTA preparations in an enzyme-linked immunospecific assay were tested in vivo for induction of resistance to the growth of transplanted tumor cells. Isotachophoresis of crude 3 M KCl extracts yielded TSTA that was immunogenic at doses between 17 and 124 μg. Isotachophoresis of TSTA partially purified from crude 3 M KCl or butanol extracts by preparative isoelectric focusing (pIEF) of 3 M KCl and butanol extracts yielded TSTA that was immunogenic over a two-fold log dose range. As little as 10 ng purified TSTA reduced tumor growth by 50%. Tumor growth reduction was specific, and immunized animals survived longer than non-immunized controls. A purification of 10,000-fold over crude 3 M KCl extracts and 2,500-fold over crude butanol extracts was obtained. These results suggest that TSTA from murine tumor cells is preparatively purified by following extraction with pIEF and then pITP.
    Materialart: Digitale Medien
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  • 10
    ISSN: 1432-0851
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Crude 3 M KCl extracts of the methylcholanthrene-induced fibrosarcoma of C3H/HeJ mice, MCA-F, were demonstrated to contain two fractions, one inducing tumor resistance and the other facilitating the outgrowth of neoplastic cell challenge. In immunoprotection tests in syngeneic C3H/HeJ mice, optimal doses of crude solubilized tumor antigen afforded only a 28% reduction in growth compared with saline-treated controls. When crude extracts were fractionated by preparative isoelectric focusing (pIEF) in a slab of superfine Sephadex G-75, significant biologic activity was demonstrated in two fractions. Fraction (Fr) 1, pI 2.5–3.6, induced potent tumor facilitation, increasing the tumor size by more than 100%, while Fr 15, pI 5.8–6.0, engendered resistance that reduced their respective biological effects to MCA-F, but not the antigenically unrelated MCA-D tumor. Thus 3 M KCl extracts contain at least two biologically active components, one immunoprotective and one tumor-facilitating. Since the weak immunoprotective activity of crude materials may represent the vectorial effect of these antagonistic components, subsequent molecular characterization of both moieties may afford insight into the complex response of hosts toward tumors. Furthermore, TSTA purified by the rapid method of isoelectric focusing may be a more suitable reagent for immunotherapy than the parent crude 3 M KCl extracts by virtue of the absence of facilitating antigens.
    Materialart: Digitale Medien
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