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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Primary cultures of fetal rat septal neurons were used to identify a membrane-associated cholinergic neurotrophic activity. Under serum-free culture conditions, ∼98% of the septal cells are neurons, and ∼6% of the neurons are cholinergic as determined immunocytochemically. Crude membranes prepared from rat hippocampal homogenates stimulate choline acetyltransferase (ChAT) activity in treated septal neurons. The membrane-associated trophic activity is apparent at lower protein concentrations than activity present in the soluble fraction and is unevenly distributed in various brain regions; it is highest in hippocampus and striatum and negligible in cerebellum. Membrane trophic activity is developmentally regulated, is heat and trypsin sensitive, and increases the rate of expression of ChAT in septal neurons. Upon gel nitration chromatography of a high-salt membrane extract, trophic activity elutes as a broad peak in the 500 kilodalton (kD) molecular mass range. Stimulation of septal neuronal ChAT activity by either crude membranes or partially purified preparations is not inhibited by antibodies against nerve growth factor (NGF), and its maximal activity is additive to maximally active doses of NGF. The results indicate that hippocampal membranes contain cholinergic neurotrophic activity which may be important for the development of septal cholinergic neurons.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    International journal of dermatology 32 (1993), S. 0 
    ISSN: 1365-4632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 277 (1976), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 690 (1993), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0851
    Keywords: Key words: Melanoma – Vaccine – Hapten – TIL – T cell activation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Treatment of metastatic melanoma patients with an autologous vaccine modified by the hapten, dinitrophenyl (DNP), produces a striking immunological effect: the induction of clinically evident inflammatory responses in metastatic tumors. Histological examination shows these tumors to be infiltrated with T lymphocytes. We studied the expression of activation markers on those cells and compared them with matched peripheral blood lymphocytes (PBL) and with lymphocytes extracted from metastases before treatment with DNP-conjugated vaccine. The median fraction of cells that were T cells in post-vaccine tumors was 41%, as compared with 9% in pre-treatment tumors, and those T cells were predominantly CD8+ (mean CD8/CD4 ratio = 5.0). A high proportion of both pre- and post-treatment infiltrating T cells expressed HLA-DR (mean ± SE = 48% ± 4%), CD69 (56% ± 7%), and ganglioside GD3 (68% ± 5%). This distinguished them from matched PBL in which expression of those markers was significantly lower (HLA-DR = 10% ± 2%; CD69 = 2% ± 0.4%; GD3 = 49% ± 4%). These changes were not accompanied by increased cell-surface expression of interleukin-2 (IL-2) receptors, either CD25 or p75, which were expressed by 1% – 2% and 12% of tumor-infiltrating lymphocytes (TIL), respectively. The pattern of activation marker expression that we identified appears to be characteristic of tissue T cells with the memory phenotype. The low expression of IL-2 receptors could indicate functional impairment of TIL in situ, perhaps because of inhibitory molecules produced by melanoma cells.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0851
    Keywords: Melanoma ; Vaccine ; Hapten ; TIL ; T cell activation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Treatment of metastatic melanoma patients with an autologous vaccine modified by the hapten, dinitrophenyl (DNP), produces a striking immunological effect: the induction of clinically evident inflammatory responses in metastatic tumors. Histological examination shows these tumors to be infiltrated with T lymphocytes. We studied the expression of activation markers on those cells and compared them with matched peripheral blood lymphocytes (PBL) and with lymphocytes extracted from metastases before treatment with DNP-conjugated vaccine. The median fraction of cells that were T cells in post-vaccine tumors was 41%, as compared with 9% in pre-treatment tumors, and those T cells were predominantly CD8+ (mean CD8/CD4 ratio=5.0). A high proportion of both pre- and posttreatment infiltrating T cells expressed HLA-DR (mean±SE=48%±4%), CD69 (56%±7%), and ganglioside GD3 (68%±5%). This distinguished them from matched PBL in which expression of those markers was significantly lower (HLA-DR=10%±2%; CD69=2%±0.4%; GD3=49%±4%). These changes were not accompanied by increased cell-surface expression of interleukin-2 (IL-2) receptors, either CD25 or p75, which were expressed by 1%–2% and 12% of tumor-infiltrating lymphocytes (TIL), respectively. The pattern of activation marker expression that we identified appears to be characteristic of tissue T cells with the memory phenotype. The low expression of IL-2 receptors could indicate functional impairment of TIL in situ, perhaps because of inhibitory molecules produced by melanoma cells.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0851
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Fourteen patients with surgically incurable malignant melanoma treated with dimethyl triazeno imidazole carboxamide (DTIC) (2 mg/kg/day i.v. × 10) and 18 patients treated with the combination of 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) (150 mg/m2 i.v.) plus vincristine (2 mg/m2 i.v.) on day 1 only, were tested for lymphocyte reactivity against melanoma cells before and after treatment. Neither chemotherapeutic regimen regularly affected lymphocyte reactivity, either in the presence of fetal calf serum or in the presence of the patients' autologous serum when tested 1 month after treatment. Three patients receiving repeated DTIC therapy and six patients receiving repeated BCNU plus vincristine therapy exhibited little variation in lymphocyte reactivity throughout the course of treatment.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Cancer immunology immunotherapy 41 (1995), S. 151-156 
    ISSN: 1432-0851
    Keywords: Cytokine mRNA ; DNP-vaccine ; Metastatic melanoma ; IFNγ ; IL-4 ; IL-10 ; TNFα
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have reported that patients with metastatic melanoma treated with an autologous, dinitrophenol-modified vaccine develop inflammatory responses at tumor sites. Histologically, these inflamed lesions are characterized by T cell infiltration, which is sometimes associated with tumor cell destruction. We tested biopsy specimens of eight subcutaneous metastases that had developed inflammation following vaccine treatment for expression of mRNA for interferon γ(IFNγ), interleukin-4 (IL-4), tumor necrosis factor α (TNFα), and IL-10. Post-vaccine, inflamed biopsies contained mRNA for IFNγ (5/8), IL-4 (4/8) or both (3/8), and for TNFα (4/7). In contrast, IFNγ mRNA was detected in only 1/17 and TNFα mRNA in 2/16 control specimens (pre-treatment lymph node metastases or non-inflamed subcutaneous metastases). mRNA for IL-10, a cytokine with anti-inflammatory properties, was detected in 24/25 melanoma metastases and was independent of lymphoid content; in situ the reverse transcriptase/polymerase chain reaction confirmed that melanoma cells were the major source. These findings may provide a new parameter by which to measure the effects of cancer immunotherapy.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Cancer immunology immunotherapy 41 (1995), S. 151-156 
    ISSN: 1432-0851
    Keywords: Key words Cytokine mRNA ; DNP-vaccine ; Metastatic melanoma ; IFNγ ; IL-4 ; IL-10 ; TNFα
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We have reported that patients with metastatic melanoma treated with an autologous, dinitrophenol-modified vaccine develop inflammatory responses at tumor sites. Histologically, these inflamed lesions are characterized by T cell infiltration, which is sometimes associated with tumor cell destruction. We tested biopsy specimens of eight subcutaneous metastases that had developed inflammation following vaccine treatment for expression of mRNA for interferon γ (IFNγ), interleukin-4 (IL-4), tumor necrosis factor α (TNFα), and IL-10. Post-vaccine, inflamed biopsies contained mRNA for IFNγ (5/8), IL-4 (4/8) or both (3/8), and for TNFα (4/7). In contrast, IFNγ mRNA was detected in only 1/17 and TNFα mRNA in 2/16 control specimens (pre-treatment lymph node metastases or non-inflamed subcutaneous metastases). mRNA for IL-10, a cytokine with anti-inflammatory properties, was detected in 24/25 melanoma metastases and was independent of lymphoid content; in situ the reverse transcriptase/polymerase chain reaction confirmed that melanoma cells were the major source. These findings may provide a new parameter by which to measure the effects of cancer immunotherapy.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Cancer immunology immunotherapy 47 (1998), S. 1-12 
    ISSN: 1432-0851
    Keywords: Key words Cyclophosphamide ; Active specific immunotherapy ; Vaccine ; Theraccine ; Melanoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This paper reviews the use of low-dose cyclophosphamide (CY) with active specific immunotherapy in patients with advanced melanoma and other metastatic cancers, and outlines the basic scientific research that supports this use. In various animal models, CY augments delayed-type hypersensitivity responses, increases antibody production, abrogates tolerance, and potentiates antitumor immunity. The mechanism of CY immunopotentiation involves inhibition of a suppressor function, as indicated by extensive work in the MOPC-315 plasmacytoma murine model. Human studies of the immunopotentiating effect of CY have yielded both positive and negative results. Toxicity associated with low-dose CY has been mild in these studies. Results of efficacy have been variable for reasons such as small sample sizes, short follow-up periods, and the weaker immunogenicity of human tumor-associated antigens. Although beneficial clinical outcomes have been observed in historically controlled trials, there are few randomized, controlled trials that evaluate outcome in relation to CY immunopotentiation of active specific immunotherapy. Additional randomized, controlled trials should be done to examine the clinical efficacy of CY immunopotentiation of therapeutic cancer vaccines.
    Type of Medium: Electronic Resource
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