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  • 1
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Science, Ltd
    European journal of neuroscience 10 (1998), S. 0 
    ISSN: 1460-9568
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: We have established a novel injury model in the central nervous system by a stereotaxic injection of ethanol into rat striatum to induce necrosis. With this model, we clarify a function of inducible nitric oxide synthase (iNOS) in a healing mechanism around a necrotic lesion. A semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) revealed that the iNOS mRNA arose at 6 h, peaked at 24 h, and declined to a lower level 48 h after an intrastriatal 5-μL ethanol injection. From in situ hybridization, this iNOS mRNA was expressed in the area surrounding the injury. By immunohistochemistry, mononuclear cells at this boundary area of necrosis were stained with anti-iNOS antibody on the first day after the injury. These cells turned out to be reactive microglia from the positive staining of GSA-I-B4, ED-1 and OX-42. Haematoxylin-eosin (HE) staining showed that neurons in this boundary area gradually disappear up to 5 days after the injury with an increment of microglial cells, and this area became cavernous. Nuclei of neurons in this area were stained positive by the terminal deoxynucleotidyl-transferase-mediated dUTP-biotin nick end-labelling (TUNEL) assay on the first day after the injury. These TUNEL-positive neurons gradually disappeared toward the third day, while microglial cells increased. L-Ng-nitro-arginine methylester (L-NAME), a competitive NOS inhibitor, administration diminished the elimination of neurons by microglia in this boundary area surrounding necrosis. Microglial NO may act as a neurotoxic agent to eliminate damaged neurons near the necrosis in the form of delayed neuronal death, and may reintegrate the neuronal circuits with functionally intact neurons.
    Materialart: Digitale Medien
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  • 2
    ISSN: 1398-9995
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: In this study, we examined the symptom scores and tumor necrosis factor-alpha (TNF-α), p55 soluble tumor necrosis factor receptor (sTNFR1), and p75 soluble tumor necrosis factor receptor (sTNFR2) levels in the sera and nasal epithelial lining fluids (ELF) of 20 patients with Japanese cedar pollinosis from the pre- to the postseason period, and compared the results with those of 10 nonallergic control subjects. The symptom scores of the allergic subjects were significantly (P〈0.01) higher than those of the nonallergic subjects during the early stage and mid-stage of the season. There were no statistical differences between the allergic and nonallergic subjects in the TNF-α levels in sera and ELF from the pre- to the post-season. In the allergic subjects, however, the levels of sTNFR1 and sTNFR2 in ELF were significantly elevated during the early stage (P〈0.05) and mid-stage (P〈0.01) of the season, whereas those in sera did not change from the pre- to the post-season period. The levels of TNF-α in ELF were more than 10 times higher than those in sera, whereas the levels of sTNFR1 and sTNFR2 in ELF were less than half of those in sera in the allergic and nonallergic subjects. These results suggest that sTNFR1 and sTNFR2 may play a role in the pathogenesis of nasal allergic reaction.
    Materialart: Digitale Medien
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  • 3
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Periodontology 2000 5 (1992), S. 0 
    ISSN: 1600-0757
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Although melanoma is a common human disease, there were few animal models in which melanoma developed at high incidence. To date, the Xiphophorus fish has been used as a model system to study melanoma formation. Studies on this fish showed the presence of a dominant oncogene, Tu, which encodes a transmembrane, tyrosine kinase of epidermal growth factor receptor type (Wittbrodt et al., Nature, 341:415–421, 1989). Recently, we succeeded in establishing novel transgenic mouse lines in which melanosis and melanocytic tumors developed stepwise by introducing another transmembrane tyrosine kinase oncogene, ret (Iwamoto et al., EMBO J., 10:3167–3175, 1991). In our transgenic mice, high levels of expression of the ret transgene induced proliferation and neoplastic transformation of melanin-producing cells. In addition, crossbreeding experiments between transgenic mice and Wv mice showed that the ret oncogene can also induce melanogenesis and melanocyte development in Wv/Wv mice.
    Materialart: Digitale Medien
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  • 4
    ISSN: 1432-0843
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Glutathione-S-transferase (GST) in one of several factors that are proposed to affect tumor sensitivity to anticancer drugs, including cisplatin (CDDP). Attempts are made herein to evaluate the significance of the enzymes in resistance to CDDP in clinical samples of gastric cancer. A total of 22 gastric cancer specimens, 16 of which were obtained with matching normal mucosae, underwent immunoblotting with polyclonal antibodies against GST-α and GST-π. At the same time, the chemosensitivity of 15 gastric cancer specimens to CDDP was evaluated by the succinic dehydrogenase inhibition (SDI) test. The expression of GST-π was detected in all the specimens, and its content in the neoplasms exhibited a significant positive correlation with that in the matched normal mucosae. The expression of GST-α was detected in 18 of 22 cancer specimens (82%), but its content in the neoplasms did not correlate with that in the matched mucosae. A comparison of the drug-sensitivity findings with the results of immunoblotting revealed a weak but interesting correlation between the protein levels of GST-α and CDDP resistance. The cellular content of GST-α correlated weakly with CDDP resistance in gastric cancer, and its quantification could contribute to prediction of the clinical effects of CDDP in patients with gastric cancer.
    Materialart: Digitale Medien
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  • 5
    ISSN: 1432-0843
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract. Glutathione-S-transferase (GST) in one of several factors that are proposed to affect tumor sensitivity to anticancer drugs, including cisplatin (CDDP). Attempts are made herein to evaluate the significance of the enzymes in resistance to CDDP in clinical samples of gastric cancer. A total of 22 gastric cancer specimens, 16 of which were obtained with matching normal mucosae, underwent immunoblotting with polyclonal antibodies against GST-α and GST-π. At the same time, the chemosensitivity of 15 gastric cancer specimens to CDDP was evaluated by the succinic dehydrogenase inhibition (SDI) test. The expression of GST-π was detected in all the specimens, and its content in the neoplasms exhibited a significant positive correlation with that in the matched normal mucosae. The expression of GST-α was detected in 18 of 22 cancer specimens (82%), but its content in the neoplasms did not correlate with that in the matched mucosae. A comparison of the drug-sensitivity findings with the results of immunoblotting revealed a weak but interesting correlation between the protein levels of GST-α and CDDP resistance. The cellular content of GST-α correlated weakly with CDDP resistance in gastric cancer, and its quantification could contribute to prediction of the clinical effects of CDDP in patients with gastric cancer.
    Materialart: Digitale Medien
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  • 6
    ISSN: 1432-0851
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The recombinant H-2Kb-erbB gene, encoding for a part of the H-2 class I antigen and the kinase domain of the V-erbB peptide, was successfully introduced into murine mastocytoma P815 variant P1.HTR cells, which resulted in low but significant cell-surface expression of the hybrid gene product. When the chimeric gene transfectant was inoculated into the CDF1 mice, it soon grew but regressed thereafter. The tumorigenicity of this transfectant was lower than the H-2Kb gene transfectant that expressed the H-2Kb antigen at a comparable level. These CDF1 mice that had received the chimeric gene transfectant obtained a high-grade anti-tumor immunity against the challenge of a high dose of parental tumor. Corresponding to these observations, anti-tumor cytotoxic T lymphocytes, which lyse parental P1.HTR cells but not syngeneic L1210 or NS-1 tumor cells, were developed in the peritoneal cavity of mice that had been inoculated with the transfectant and parental tumor. Definite antibody activity binding to parental P1.HTR tumor cells was also demonstrated in the sera of these mice, precipitating 40-kDa, 74-kDa and 98-kDa molecules from the surface of the radiolabeled P1-HTR tumor cells. The results suggested that the chimeric H-2-erbB gene transfectant efficiently triggers both cellular and humoral anti-tumor immune responses.
    Materialart: Digitale Medien
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  • 7
    ISSN: 1436-2813
    Schlagwort(e): xenograft ; complement inhibitor ; transgenic
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract To solve the chronic donor organ shortage, the pig is considered to be a possible donor candidate for human transplantation. However, hyperacute rejection occurs due to the activation of the complement cascade. Therefore, the introduction of human complement inhibitors into animal cells has been proposed as a means to prevent such exologous complement activation. To investigate the extent to which complement inhibitors are resistant to human sera in discordant animals, we established transgenic mice lines which expressed either human decay-accelerating factor (DAF) and/or homologous restriction factor 20 (HRF20) using microinjection methods. Human sera were injected into (a) 10 control mice, (b) 10 DAF-transgenic mice, (c) 10 HRF20-transgenic mice, and (d) 10 DAF and HRF20-transgenic mice. The results showed that all the mice in groups a, b, and c died immediately after injection. Three of the mice in group d died, while seven survived but showed hyperpnea and low activity. The pathological findings of groups a, b, and c included severe coagulation; however, the survivors of group d showed less severe symptoms. The above findings thus suggest that both DAF and HRF20 tend to prevent complement activation to some extent; however, its effectiveness is not considered to be sufficient for clinical use in transplantation.
    Materialart: Digitale Medien
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  • 8
    ISSN: 1573-0832
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract A close correlation was observed between body weight and length of the survival time of mice inoculated intravenously (i.v.) with Cryptococcus neoformans (p〈0.001). An endotoxic substance of C. neoformans (Cr-ET) increased the susceptibility of mice to i.v. infection of C. neoformans only when more than 50 μg of Cr-ET was injected i.v. 24 hours before infection. Intraperitoneal (i.p.) administration of dimethyl sulfoxide which is found to enhance bacterial infection did not enhance death rate of mice infected i.p. with C. neoformans.
    Materialart: Digitale Medien
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  • 9
    ISSN: 1432-1211
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract Early and late primary IgM antibody responses of mice to Thy-1.1 antigens showed different antigenic and cellular requirements. We studied genetic controls of the early primary responses, which could be induced by subcellular thymocyte antigens independently of host T-cell activity. All Thy-1.2 mouse strains of Igh a(BALB/c and BC8), Igh-V aCb(BAB14), Igh d(AKR/Cum), Igh j(CBA/J, C3H/HeN, C3H.SW, and C3H.JK), and Igh n(NZB) definitely responded early to Thy-1.1 antigens from AKR/J (Igh d), A.Thy-1.1 (Igh e), or B10.Thy-1.1 (Igh b) mice or SD rats, whereas all strains of Igh b(C57BL/6, C57BL/10, B10.D2, B10.BR, B10.A, CB20 and CWB), Igh c(DBA/2), Igh e(A/J), and Igh o(C.AL20) responded poorly to the same antigens. This contrasts with the observation that both strains of Igh j(C3H/HeN) and Igh b(B10.BR) responded well at later times. As was the case for late responses, the matching of H-2 between donor and recipient resulted in early responses of exceptional quality in high-responder strains. It was concluded that under the influence of H-2, whose incompatibility between donor and recipient partially interferes with responses, early but not late primary Thy-1.1-specific antibody responses are selectively controlled by Igh-V or closely linked Ir gene(s) as a new V Hmarker.
    Materialart: Digitale Medien
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  • 10
    Digitale Medien
    Digitale Medien
    Springer
    Immunogenetics 30 (1989), S. 70-75 
    ISSN: 1432-1211
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract Immunogenicity of allogeneic immunoglobulins in mice were studied, measuring the allotype-specific antibody activity by agglutination of allogeneic antibody-coated red blood cells. It was found that the serum from C.B-20 mice (Igh b , BALB/c-congenic) was uniquely immunogenic in BALB/c mice for allotype antibody response. Whereas the C57BL/6 (Igh b ) serum was immunogenic only when heat aggregated and/or combined with adjuvant, the ultracentrifugation-deaggregated C.B-20 serum was definitely immunogenic when administered in a moderate dose (100 μl/mouse). Even more surprising was the fast that very low doses (0.01–0.1 μl) of soluble C.B-20 serum, but not C57BL/6 serum, down regulated the allotype-specific response effectively. Genetic analysis on congenic mice suggested that the immunogenicity is controlled by donorIgh orIgh-V(Id-C.B) inasmuch as the serum from BALB/c-congenic C.B-20 (Igh-V b C b ), but not BALB/c-congenic BAB/14 (Igh-V a C b ), mice was active in BALB/c mice in soluble form. Further studies showed that the Id-C.B was dominantly expressed on the immunoglobulins of (BALB/c×C.B-20)F1 and (C56BL/6×C.B-20)F1 strains, and was originally derived from the C57BL/Ka strain. The major determinant for the antibody production was encoded inIgh-C, but not inIgh-V. It is suggested thatId-C.B controls the allotype-specific antibody response in an unusual manner, possibly acting as a unique determinant activating helper T cells.
    Materialart: Digitale Medien
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