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  • 1
    ISSN: 1365-3083
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Functional dendritic cells (DC) are professional antigen-presenting cells (APC) and can be generated in vitro from healthy as well as from leukaemic cells from acute myeloid leukemia (AML) patients giving rise to APC of leukaemic origin-presenting leukaemic antigens. We describe the generation and characterization of DC from different mononuclear cell (MNC) fractions from 50 AML patients under different serum-free culture conditions, determine the optimal culture conditions and compare the results with that from 23 healthy donors. In parallel cultures, we compared DC harvests after 7- or 14-day culture, with total or adherent MNC or T-cell depleted MNC or peripheral blood (PB) or bone marrow-MNC (BM–MNC), thawn or fresh MNC, in Xvivo or CellGro serum-free media, ±10% autologous plasma or ±FL. In detail, we could show that AML–DC harvests were higher after 10–14 days culture (healthy DC: 7 days); total or adherent PB or BM–MNC fractions yield comparable DC counts, however, from magnetic cell sorting (MACS)-depleted MNC fractions or thawn MNC lower DC counts can be generated. Whereas the addition of FL increases the DC harvest, the addition of autologous plasma in many cases has inhibitory influence on DC maturation. CellGro and Xvivo media yield comparable DC counts. Optimal harvest of vital and mature DC from AML samples was obtained with a granulocyte/macrophage-colony stimulating factor, interleukin-4, FL and tumour necrosis factor-α-containing serum-free Xvivo medium after 10–14 days of culture (36/26% DC; 38/64% vital DC; 46/51% mature DC were generated from AML/healthy MNC samples). Surface marker profiles (e.g. costimulatory antigen expressing) of DC obtained from AML samples were comparable with that of healthy DC. The leukaemic derivation of AML–DC was demonstrated by the persistence of the clonal cytogenetic aberration in the DC or by coexpression of leukaemic antigens on DC. Autologous T-cell activation of leukaemia-derived DC was demonstrated in cases with AML. Autologous T cells proliferate and upregulate DC-contact-relevant antigens. We demonstrate that the generation of leukaemia-derived DC is feasable in AML under serum-free culture conditions giving rise to DC with comparable characteristics as healthy DC and offering an anti-leukaemia-directed immunotherapeutical vaccination strategy in AML.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    ISSN: 1365-3083
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Functional dendritic cells (DC) are professional antigen-presenting cells (APC) and can be generated in vitro from healthy as well as from leukaemic cells from AML patients giving rise to APC of leukaemic origin presenting leukaemic antigens. In a comparative methodological analysis of 50 AML samples, we could already show that leukaemia-derived DC can regularly be generated under serum-free culture conditions. In this study, we describe the generation and characterization of DC from different mononuclear cell (MNC) fractions from 24 myelodysplastic syndrome (MDS) patients under those different serum-free culture conditions, determine the optimal culture conditions and compare the results with that from 23 healthy donors. In parallel cultures, we compared DC harvests after 7- or 14-day culture, with total or adherent MNC or T-cell-depleted MNC or PB or BM–MNC, thawn or fresh MNC, in Xvivo or CellGro serum-free media, ±10% autologous plasma or ±FL. In detail, we could show that MDS–DC harvests compared to healthy DC were higher after 10- to 14-day culture; total or adherent PB or BM–MNC fractions yield comparable DC counts; however, from MACS-depleted MNC fractions or thawn MNC lower DC counts can be generated. Whereas the addition of FL increases the DC harvest, the addition of autologous plasma in many cases has inhibitory influence on DC maturation, CellGro and Xvivo media yield comparable DC counts. Optimal harvest of vital and mature DC from MDS samples was obtained with a GM-CSF, IL-4, FL and TNF-α containing serum-free Xvivo medium after 10–14 days of culture (18/26% DC; 54/64% vital DC; 59/51% mature DC were generated from MDS/healthy MNC samples). Surface marker profiles (e.g. costimulatory antigen expression) of DC obtained from MDS samples were comparable with that of healthy DC. The leukaemic derivation of MDS–DC was demonstrated by the persistence of the clonal cytogenetic aberration in the DC or by coexpression of leukaemic antigens on DC. Autologous T-cell activation of leukaemia-derived DC was demonstrated in cases with MDS. Autologous T cells proliferate and upregulate DC-contact-relevant antigens. We are the first who demonstrate that the generation of leukaemia-derived DC is feasible not only in AML but also in MDS under serum-free culture conditions giving rise to DC with comparable characteristics as healthy DC and offering an antileukaemia-directed immunotherapeutical vaccination strategy in AML and MDS.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    ISSN: 1365-2133
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Summary Chronic graft-versus-host disease after bone marrow transplantation presents, in a few cases, as mild to severe scleroderma-like changes. Patients with chronic graft-versus-host disease with and without sclerodermatous skin changes were analysed for antinuclear autoantibodies (ANA) and antinucleolar autoantibodies (ANoA) and the results correlated with disease symptoms and histocompatibility locus antigen (HLA) pattern. Nineteen patients with chronic graft-versus-host disease and scleroderma-like skin changes. 18 with chronic graft-versus-host diseae without scleroderma. and 17 controls on immunosuppressive treatment were screened for ANA and ANoA using enzyme-linked immunosorbent assay, immunodiffusion and immunoblot techniques. Four patients with severe scleroderma had antibodies to topoisomerase I. two had antibodies against PM-Scl. both characteristic serological findings in idiopathic systemic scleroderma. One patient had La/SSB antibodies and, in three cases, antibodies to the nucleolar antigen C23 (nucleolin) could be identified. A possible correlation between antinucleolin antibodies and disease activity was observed. HLA-Al. -B1. and -B2 were found significantly more often in patients with scleroderma-like symptoms in comparison to patients without scleroderma-like symptoms. Chronic graft-versus-host disease with seleroderma-like manifestations can be associated with the occurrence of ANA specific for idiopathic scleroderma. The development of seleroderma after bone marrow transplantation might have a HLA-linked genetic background.
    Materialart: Digitale Medien
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  • 4
    ISSN: 1432-1440
    Schlagwort(e): Bone marrow transplantation ; Aplastic anaemia ; Knochenmarktransplantation ; Aplastische Anämie
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Zusammenfassung Im Rahmen der Arbeitsgemeinschaft Knochenmarktransplantation — München (AG-KMT) wurden vom März 1975 bis Mai 1980 insgesamt 12 Patienten wegen schwerer, aplastischer Anämie mit Knochenmarktransplantation (KMT) behandelt. Sechs Patienten überleben derzeit mit normalem Blutbild und Knochenmark zwischen 10 Monaten und mehr als 5 Jahren nach KMT von HLA-identischen Geschwistern, eine Patientin steht noch in ambulanter Behandlung wegen lokalisierter, chronischer Graft-versus-Host Krankheit (GvHK), fünf Patienten sind klinisch gesund. Sechs Patienten starben, ein Patient starb am Tag vor KMT mit Hirnblutung, drei Patienten 32, 40 und 55 Tage nach KMT an den Folgen der Transplantatabstoßung, einer an schwerer GvHK 85 Tage nach KMT und einer 87 Tage nach KMT vermutlich an interstitieller Pneumonie nach Hirnblutung. Drei von 6 Patienten, die nur mit Cyclophosphamid (CY) vorbehandelt waren, starben infolge Abstoßung des Transplantates. Zwei erwachsene Patienten, die mit CY und „total lymphoid irradiation“ vorbehandelt waren, und drei Kinder, die nach KMT unbestrahlte Leukocytenkonzentrate von Knochenmarkspender erhalten hatten, stießen das Transplantat nicht ab. Die Ergebnisse der AG-KMT sind vergleichbar denen großer, spezialisierter Zentren für KMT und zeigen die Möglichkeiten einer Heilung schwerer aplastischer Anämien durch KMT von HLA-identischen Geschwistern. Die Erfolge sind besser bei frühzeitiger KMT.
    Notizen: Summary From March 1975 until May 1980 twelve patients with severe aplastic anemia were grafted with bone marrow from HLA-identical siblings by the Munich Cooperative Group for Bone Marrow Transplantation. Six patients are alive between 10 months and more than 5 years after grafting with normal blood values and marrow. One patient is treated as an out patient for chronic localized graft-versus-host disease (GvHD), five patients are well and without treatment. Six patients have died, one patient with a cerebral hemorrhage the day before transplantation, three patients following rejection of grafts 32, 40 and 55 days after grafting, one patient with severe GvHD 85 days after grafting and one patient, probably with interstitial pneumonia, following cerebral hemorrhage. Three of 6 patients who were conditioned with Cyclophosphamide (CY) only died following rejection of the graft. Two adults who were conditioned with CY and “total lymphoid irradiation” and three children, who were given unirradiated leukocyte concentrates from the marrow donor after grafting, did not reject their grafts. The results of the Munich-Cooperative Group for Bone Marrow Transplantation are comparable to those of large, specialized centers for bone marrow transplantation, they indicate possibilities of cure of severe aplastic anemia by marrow grafts from HLA-identical siblings. They confirm that better results are obtained with earlier transplantation in the course of the disease.
    Materialart: Digitale Medien
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  • 5
    Digitale Medien
    Digitale Medien
    Springer
    Diabetologia 18 (1980), S. 463-469 
    ISSN: 1432-0428
    Schlagwort(e): Muscle triglycerides ; muscle glycogen ; insulin dependent diabetes mellitus ; insulin deficiency ; glycaemic control ; non-esterified fatty acids ; glycerol ; exercise
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Muscle triglycerides and glycogen were measured in biopsy specimens of the vastus lateralis muscle before and after 1 h of ergometric exercise at 50 to 60% of maximal capacity (i. e. at a pulse rate during exercise of 180 minus age) in 3 groups of 19 to 35 year old, non-obese male subjects: 10 normals, 10 insulin dependent diabetic patients in relatively good control and 10 poorly controlled insulin dependent diabetic patients in whom insulin was withdrawn 24 h prior to examination. At rest in all subjects muscle triglyceride content was positively correlated with serum triglycerides (p〈0.001) and blood glucose (p〈0.05), resulting in elevated muscle triglyceride stores in the insulin deficient diabetic patients (17.9 ±1.8 μmol/g protein vs. 13.4±1.3 and 9.4±1.2 in the normal subjects and the well controlled diabetic patients; p〈0.05 and 〈0.001). During exercise, utilisation of muscle triglycerides and glycogen were directly related to content at rest (p〈0.001), including the insulin-deprived patients with decreased glycogen. The decrease of muscle fat was associated with a rise in serum glycerol (p〈0.001) and nonesterified fatty acids (p〈0.001) during exercise.
    Materialart: Digitale Medien
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  • 6
    ISSN: 1432-0428
    Schlagwort(e): Insulin degrading enzyme activity ; insulin binding ; insulin resistance ; Type 2 diabetes ; erythrocytes
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Specific insulin degrading enzyme activity of erythrocytes was determined in relation to erythrocyte insulin binding in 16 healthy subjects, 14 Type 1 (insulin-dependent) and various groups of Type 2 (non-insulin-dependent) diabetic patients (n = 39). Degrading activity was increased in Type 2 diabetic patients on sulphonylureas, as well as in a subgroup with good metabolic control (p〈0.001) and in patients with secondary failure to oral therapy (p〈0.02); degrading activity returned to normal in the latter patients after 1 week of insulin treatment. Highest degrading activity was found in insulintreated, yet insulin-insensitive patients (daily insulin dose 〉80 U). Degrading activity was significantly correlated in healthy subjects both with circulating insulin concentrations and maximal specific insulin binding. In contrast, in Type 2 diabetic subjects, degrading activity was inversely correlated with serum insulin with no apparent association with maximal specific insulin binding except in those patients given 1 week of insulin treatment. High erythrocyte insulin degrading enzyme activity might be a common feature in the insulin-insensitive Type 2 diabetic patient and might occur subsequent to some aspect of insulin deficiency at the tissue level.
    Materialart: Digitale Medien
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  • 7
    ISSN: 1432-0584
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Zusammenfassung Ein Junge mit schwerer Knochenmarkaplasie und ein Mädchen mit rezidivierender akuter lymphatischer Leukämie wurden nach entsprechender immunsuppressiver und antileukämischer Vorbehandlung mit Knochenmark von HL-A-identischen, MLC-negativen Geschwistern transplatiert. Beide Kinder sind 7 bzw. 2 Monate nach Knochenmarkaplasie oder akuter lymphatischer Leukämie im Rezidiv in Betracht gezogen werden, wenn HL-A-identische, MLC-negative Geschwister zur Verfügung stehen.
    Notizen: Summary A boy with severe Aplastic Anemia (AA) and a girl with Acute Lymphoblastic Leukemia (ALL) in relapse have been grafted with marrow from HL-A identical, mixed leukocyte culture (MLC) negative siblings after appropriate immunosuppressive and antileukemic therapy. Both of them are well 7 and 2 months after transplantation respectively. Bone marrow transplantation should be considered in children with AA and ALL in relapse, if HL-A identical, MLC negative sibling are available.
    Materialart: Digitale Medien
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  • 8
    ISSN: 1432-0584
    Schlagwort(e): Adriamycin ; Toxocity ; Autologous bone marrow transplantation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary We investigated the toxicity of adriamycin (ADM) in dogs with regard to autologous bone marrow transplantation (BMT). Gastrointestinal toxicity limited the dose of ADM in single administration (3.0 mg/kg) and chronic cardiotoxicity in repeated administration (9×1.5 mg/kg every two weeks). The recovery of hemopoiesis was complete within 25 days after single and repeated doses of ADM as indicated by the restoration of blood counts and concentration of hemopoietic precursors (CFUc) as well as proliferate activity of bone marrow. At this time bone marrow was obtained and reinfused after total body irradiation (TBI) with 10 Gy. Single and repeated doses of 1.5 mg/kg ADM did not delay recovery of blood counts after autologous BMT as compared to transplantation of untreated marrow — in contrast a single dose of 3.0 mg/kg ADM did. Our results indicate that toxicity of ADM is not influenced by autologous BMT. Previous shorter therapy with conventional doses of ADM does not preclude autologous BMT.
    Materialart: Digitale Medien
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  • 9
    ISSN: 1432-0584
    Schlagwort(e): Biopterin ; Bone marrow transplantation ; Hemopoiesis ; Reticulocytes
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Bone marrow aplasia was induced by fractionated whole body irradiation with 3000 R and restitution was started by autologous bone marrow transplantation. During the period of aplasia the amount of buffy coat biopterin clearly followed the decline of leukocytes and, vice versa, during reconstitution it largely paralleled their increase in number. The amount of red cell biopterin closely correlated with the number of reticulocytes rather than with the fairly constant values for hematocrit or of erythrocytic protein. Thereby it clearly followed the various periods of red cell recovery. The amount of cellular biopterin, its concentration with respect to cell number or to unit of protein and the percentage distribution of biopterin among the cell fractions are presented as characteristics of the activity of hemopoietic cell proliferation.
    Materialart: Digitale Medien
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  • 10
    ISSN: 1432-0584
    Schlagwort(e): CML ; Busulfan ; Hydroxyurea ; Interferon-alpha ; Duration of chronic phase ; Prospective study
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary For palliative therapy during the chronic phase of CML busulfan has proved to be the drug of choice. During the past years hydroxyurea and also interferon-alpha have gained increasing significance since they might prolong the duration of the chronic phase. In a multicenter study it is being determined, whether the use of hydroxyurea or of interferon-alpha instead of busulfan prolongs the duration of the chronic phase of Philadelphia positive CML. Additional goals are the examination of whether the types of disease evolution and the terminal phases differ between the treatment groups, and the prospective recognition of prognostic criteria for the duration of the chronic phase of CML. By December 31, 1987, 326 CML-patients had been randomized, 150 for busulfan, 150 for hydroxyurea and 26 for interferon-alpha. The average age is 50 years. 59 patients reached the end of the chronic phase, 55 died. The mean observation time of all patients is 1.34 years. At present no significant difference in survival is recognizable between the busulfan and hydroxyurea groups. Fewer adverse effects have been observed in the hydroxyurea group. Philadelphia chromosome negative patients show a higher average age and tend to have lower white blood cell and platelet counts. The number of patients having received interferon-alpha is still too small to allow evaluation. This report intends to document organization and progress of this study which to our knowledge is, at present, the largest ongoing prospective multicenter study on the therapy of CML.
    Materialart: Digitale Medien
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