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  • 1
    Electronic Resource
    Electronic Resource
    H2-M polymorphism in mice susceptible to collagen-induced arthritis involves the peptide binding groove (1996)
    Springer
    Immunogenetics 44 (1996), S. 19-26 
    Details
    ISSN: 1432-1211
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The ability to develop type II collagen (CII)-induced arthritis (CIA) in mice is associated with the major histocompatibility I-A gene and with as yet poorly defined regulatory molecules of the major histocompatibility complex (MHC) class II antigen processing and presentation pathway. H2-M molecules are thought to be involved in the loading of antigenic peptides into the MHC class II binding cleft. We sequenced H2-Ma, H2-Mb1, and H2-Mb2 genes from CIA-susceptible and -resistant mouse strains and identified four different Ma and Mb2 alleles and three different Mb1 alleles defined by polymorphic residues within the predicted peptide binding groove. Most CIA-resistant mouse strains share common Ma, Mb1, and Mb2 alleles. In contrast, H2-M alleles designated Ma-III, Ma-IV, Mb1-III, and Mb2-IV could be exclusively identified in the CIA-susceptible H2 r and H2 q haplotypes, suggesting that allelic H2-M molecules may modulate the composition of different CII peptides loaded onto MHC class II molecules, presumably presenting “arthritogenic” epitopes to T lymphocytes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002510050085
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  • 2
    Electronic Resource
    Electronic Resource
    Early Postoperative Transcranial Sonography (TCS), CT, and MRI after Resection of High Grade Glioma: Evaluation of Residual Tumour and its Influence on Prognosis (2000)
    Springer
    Acta neurochirurgica 142 (2000), S. 1089-1097 
    Details
    ISSN: 0942-0940
    Keywords: Keywords: Brain neoplasms; magnetic resonance imaging; tomography, X-ray computed; ultrasonics.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary ¶ Purpose. In this prospective study the results of multimodal postoperative neuro-imaging were related to the survival of patients with high grade gliomas.  Methods. All 73 patients included underwent microsurgical tumour resection and had postoperative CT and transcranial sonography (TCS) examinations. In addition, 35 of the 73 patients received an early postoperative MRI. Patients were followed up for at least one year.  Findings. At the end of the 7 year study period 56 patients had died. The median survival time was 371 days. Survival rate was significantly higher in patients with anaplastic astrocytomas and inpatients displaying complete tumour resection on MRI (log-rank-test, p〈0.05) or a small postoperative residual tumour bulk on TCS (log-rank-test, p〈0.05). Cox proportional hazards model identified histological tumour grade, postoperative Karnofsky index, complete resection based on MRI and small postoperative residual tumour mass on TCS as independent predictors of survival.  Interpretation. This study demonstrates that early postoperative neuro-imaging has prognostic implications for the survival of patients with high grade gliomas. According to our results postoperative imaging with MRI and TCS is a valuable prognostic with regard to patient survival and should therefore be implemented in postoperative follow-up. It also helps to evaluate the efficacy of adjuvant therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s007010070035
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  • 3
    Electronic Resource
    Electronic Resource
    Recognition of Human Renal Cell Carcinoma and Melanoma by HLA-A2-Restricted Cytotoxic T Lymphocytes is Mediated by Shared Peptide Epitopes and Up-Regulated by Interferon-γ (1996)
    Oxford, U.K. and Cambridge, USA : Blackwell Science Ltd
    Scandinavian journal of immunology 44 (1996), S. 0 
    Details
    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
    URL: http://dx.doi.org/10.1046/j.1365-3083.1996.d01-304.x
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  • 4
    Electronic Resource
    Electronic Resource
    Segregation of Effector Mechanisms in a Tumour-Specific CD8+ T-Cell Clone Correlates with CD30 Expression (2001)
    Oxford, UK : Blackwell Science Ltd
    Scandinavian journal of immunology 54 (2001), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In this study we have analyzed CD30-antigen expression in three melanoma-directed cytotoxic T lymphocyte (CTL) clones with a T helper 0 (Th0)-like cytokine secretion profile (i.e. interleukin (IL)-4, IL-5, and interferon (IFN)-γ). We show that all CTL clones expressed high levels of CD30 upon contact with the autologous tumour cells. One CTL clone, termed A2 with a monoclonal feature was selected for further analyses and found its CD30 expression dependent on the presence of IL-4. Functionally, a CD30-expressing A2 CTL was capable of producing higher amounts of IFN-γ (up to 1.5-fold) and IL-4 (up to two-fold) than its CD30− counterpart. Furthermore, CD30-positive A2 CTL displayed an at least three-fold greater proliferative response to the tumour cell stimulation, contrasting with CD30− CTL. However, the antitumour cytotoxic activity of A2 CTL was not modulated by the CD30 expression. These results suggest that CD30 antigen can be inducible on a subset of tumour-directed CD8+ CTL, and that this subset of cells may have profound effector functions, such as cytokine secretion, proliferation, and cytotoxicity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-3083.2001.00971.x
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  • 5
    Electronic Resource
    Electronic Resource
    Interleukin-7 (IL-7) in Colorectal Cancer: IL-7 is Produced by Tissues from Colorectal Cancer and Promotes Preferential Expansion of Tumour Infiltrating Lymphocytes (1997)
    Oxford, U.K. and Cambridge, USA : Blackwell Science Ltd
    Scandinavian journal of immunology 45 (1997), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Despite increasing survival rates for patients with colorectal cancer, additional treatment options are required, including active or passive immunotherapy for patients with metastatic disease. Freshly harvested colorectal cancer specimens and in vitro cultured colorectal cancer cell lines were examined for IL–7 protein secretion in order to examine the potential role of this cytokine in the interaction between tumour cells and the host immune system. Freshly harvested colorectal cancer specimens (21/21), or normal adjacent mucosa (3/3), as well as long-term established colorectal cancer cell lines (3/4) exhibited IL-7 mRNA expression as detected by RT-PCR and confirmed by Southern Blot analysis. Freshly harvested colorectal cancer tissue (16/18), or long-term established colorectal cancer cell lines (2/4) secreted in vitro IL-7 as detected by ELISA. In contrast, breast, pancreatic, or lung cancer cell lines, as well as several haematopoietic cancer cells lines, tested negative for IL-7 mRNA and protein. The authors tested different cytokines (IL-1β, IL-2, IL-7, or a combination of IL-1β/IL-7) in vitro for the ability to expand tumour - infiltrating T lymphocytes (TIL) from individual patients (n=9) with colorectal cancer. TIL populations were tested at day 14 after in vitro propagation for phenotypic analysis by FACS and for reactivity directed against NK and LAK sensitive target cells and autologous cancer cells as measured by cytotoxicity and cytokine release. TIL obtained from colorectal cancer lesions can be efficiently expanded in the presence of IL-7, some (3/9) of which appear to exhibit autologous tumour recognition as measured by cytolytic effector functions and by detection of IFNγ and TNFα release. Detection of IL-7 mRNA expression in colorectal cancer, in normal mucosa adjacent to tumour, as well as the ability of colorectal cancer tissue to secrete IL-7, raises new questions about the biology of the host / tumour interactions in colorectal cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-3083.1997.d01-384.x
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  • 6
    Electronic Resource
    Electronic Resource
    Gene polymorphism at position –308 of the tumor necrosis factor α promotor is not associated with disease progression in multiple sclerosis patients (1999)
    Springer
    Journal of neurology 246 (1999), S. 949-954 
    Details
    ISSN: 1432-1459
    Keywords: Key words Multiple sclerosis ; Tumor-necrosis factor ; Genetic polymorphism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Tumor necrosis factor-α (TNFα) is a pluripotent proinflammatory cytokine and is thought to play an important role in the inflammatory process of multiple sclerosis (MS). A G→A transition in the TNFα promotor at position –308 (TNF2 allele) has been shown to be associated with increased TNFα production. This study was designed to detect wether the TNF2 allele is associated with disease progression in MS. We examined the TNFα–308 polymorphism with an allelic discrimination PCR to detect the G→A transition in the genomic DNA of 283 MS patients from Germany and in 72 patients with amyotrophic lateral sclerosis (ALS) and 66 with stroke from the same genetic background who served as controls. Disease severity was defined by the progression index (PI) and by progression to the important clinical landmarks of Extended Disability Status Score (EDSS) 3.5 and 6. In addition, we evaluated the TNFα mRNA expression in whole blood with quantitative PCR. No differences were found between the presence of the TNF2 allele in MS, ALS, or stroke patients. Among the MS patients the TNF2 allele was not associated with a certain disease course. No association was found between the accumulation of neurological deficits and progression to clinical landmarks. Although MS patients with the TNF2 allele tended to progress more rapidly from EDSS 3.5 to EDSS 6 this difference was nonsignificant (P = 0.2). Nevertheless, we observed significantly higher TNFα mRNA expression in blood cells of stable patients carrying the TNF2-allele in comparison to the group with the wild type (P = 0.024). To examine the effect of genetic background we examined the DNA of 60 MS patients and 20 healthy controls in a Cypriot population of Greek origin. There was a significantly lower frequency of the TNF2 allele in the Cyprus population than in Germans (P = 0.01). No significant differences were found between the frequencies of the TNF2 allele in Cypriot MS patients and controls. Although the TNF2 allele is associated with higher TNFα mRNA baseline levels, our data indicate that this allele appears not to contribute to MS susceptibility or severity. In addition our data demonstrate that the TNFα–308 polymorphism is segregated differentially in two European populations of different genetic origin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004150050489
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  • 7
    Electronic Resource
    Electronic Resource
    Autoreactivity to mouse C1q in a murine model of SLE (1995)
    Springer
    Rheumatology international 15 (1995), S. 117-120 
    Details
    ISSN: 1437-160X
    Keywords: SLE ; C1q ; Autoimmunity ; Rheumatoid arthritis ; Autoantibodies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A large proportion of systemic lupus erythematosus (SLE) patients develop glomerulonephritis, coincident with the appearance of autoantibodies to C1q, the Fcrecognizing collagen-like subcomponent of the first component of complement, C1. The MRL/lpr/lpr mouse is an established model for SLE, developing both antinuclear and anti-type II collagen autoantibodies, and rheumatoid factors(s), exhibiting reduced complement levels and later on developing glomerulonephritis and often arthritis. We report here an age-dependent decrease in serum C1q levels coincident with the development of IgG2b autoantibodies reactive with mouse C1q in MRL/lpr/lpr mice. Unlike IgG2b, although high levels of IgM, IgG1 and IgG2a are present in these mice, few, if any, antibodies of these sub-classes reactive with mouse C1q were observed in this study. This is the first report of autoantibodies against autologous C1q in an animal model, and the results should facilitate in clarification of the roles of C1q and autoantibodies reactive with C1q in SLE, as well as their potential connection with glomerulonephritis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00302128
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