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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The N141I missense mutation in presenilin (PS) 2 is tightly linked with a form of autosomal dominant familial Alzheimer's disease (AD) in the Volga German families. We have generated transgenic mouse lines overexpressing human wild-type or mutant PS2 under transcriptional control of the chicken β-actin promoter. In the brains of transgenic mice, the levels of human PS2 mRNA were found to be five- to 15-fold higher than that of endogenous mouse PS2 mRNA. The amyloid β-protein (Aβ) 42 levels in the brains of mutant PS2 transgenic mice were higher than those in wild-type PS2 transgenic mice at the age of 2, 5, or 8 months. In addition, the Aβ42 levels appeared to increase steadily in the mutant PS2 transgenic mouse brains from 2 to 8 months of age, whereas there was only a small increase in wild-type transgenic mice between the ages of 5 and 8 months. There was no definite difference in the levels of N-terminal and C-terminal fragments between wild-type and mutant PS2 transgenic mice at the age of 2, 5, or 8 months. These data show a definite effect of the PS2 mutation on an age-dependent increase of Aβ42 content in the brain.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2307
    Keywords: Key words Thrombospondin-1 ; p53 ; Colon cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  If activation of the p53 gene is involved in the progression or metastasis of colon cancer, it may affect the angiogenic phenotype in vivo. To verify this hypothesis, we studied the correlation between p53 accumulation and expression of thrombospondin-1 (TSP1) in colon cancer specimens. Levels of TSP1 gene expression were estimated by Northern blotting in 65 colon cancers. Accumulation of p53 and the distribution of TSP1 protein were evaluated immunohistochemically. Various levels of TSP1 gene expression were seen in colon cancers, while p53 accumulation was confirmed in 42 of the 65 colon cancers. The level of TSP1 gene expression demonstrated a significant inverse correlation with p53 accumulation in colon cancer. Colon cancer cells expressed TSP1 protein and p53 accumulation reciprocally in the same nests. These results suggest that alterations in the tumour suppressor gene p53 may inhibit TSP1 expression in colon cancer.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The responses of 14 lines of human lung cancer xenografts in BALB/c-nu/nu mice to eight known antitumor agents were investigated. These xenografts consisted of four small-cell carcinomas (SCLC) and ten non-small-cell carcinomas (four large cell, three squamous cell, and three adenocarcinomas; NSCLC). The doses used in the experiments were the maximum tolerated dose (MTD) in nude mice and the “rational dose” (RD), the latter considered to be pharmacokinetically equivalent to the clinical dose. When given at MTDs, all drugs except 5-fluorouracil (5-FU) and methotrexate (MTX) were extremely effective against NSCLC as well as SCLC. The response rates of drug-sensitive SCLC to mitomycin C (MMC), ACNU, and vinblastine (VLB) were 100%, and those to Adriamycin (ADR) and vincristine (VCR) were 75%. In addition, the response rates of even drug-resistant NSCLC to MMC and VLB were 70% and 90%, respectively. In contrast, the response rates of NSCLC to RDs of the drugs were reduced to 〈40% and corresponded well to the respective clinical rates. In SCLC, a good correlation of experimental and clinical response rates was observed with four drugs [cyclophosphamide (CPM), ACNU, VLB, and 5-FU]. As a result, we emphasize that a more reasonable prediction of the clinical effectiveness of antitumor agents can be made by a protocol using clinically equivalent doses.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-069X
    Keywords: Epidermal malignancies ; Immunohistochemistry ; Human skin (experimental model) ; Neoplastic cells ; SCID mouse ; Xenografts
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Using a full-thickness skin grafting technique, lesional skin from various human neoplastic and preneoplastic skin diseases was transplanted onto SCID (severe combined immunodeficiency) mice. Of 27 grafted lesions, 21 were successfully accepted by the mice and maintained in good condition. All these accepted grafts were finally excised 10–101 days after transplantation for histological examination. In most grafts, the characteristic histological configurations of each disease were well preserved. Immunohistochemical study using monoclonal antibodies to human blood group antigens ABH revealed that some elements of the grafts such as sweat glands were clearly positive, confirming that the tissue was from human skin. Neoplastic (atypical) cells were detected in 9 of 17 accepted grafts containing neoplastic cells from the beginning. The detection rates for neoplastic cells were very high (90%) in grafts from precursor lesions of squamous cell carcinomas such as Bowen's disease (5/5 specimens) and thermal keratosis (2/3). In contrast, no definite neoplastic cells were found in two grafts from extramammary Paget's disease and five grafts from the radial growth component of malignant melanoma. In most of the grafts from latter two diseases, characteristic histological configurations such as elongation of the rete ridges were maintained, suggesting that the neoplastic cells were selectively eliminated from the grafts. Split-thickness grafts of normal human skin were accepted and remained in a good condition for as long as 6 months. Engraftment of human lesional and non-lesional skin onto SCID mice therefore may well provide a useful in vivo experimental model of human skin diseases.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0878
    Keywords: Key words: Epithelial-mesenchymal interaction ; Human epidermal keratinocytes ; Human fibroblasts ; Xenotransplantation ; Mouse (BALB/c nu/scid)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. We examined effects of fibroblasts of different origin on long-term maintenance of xenotransplanted human epidermal keratinocytes. A suspension of cultured epidermal cells, originating from adult human trunk skin, was injected into double mutant immunodeficient (BALB/c nu/scid) mice subcutaneously, with or without cultured fibroblastic cells of different origin. At one week after transplantation, the epidermal cells generated epidermoid cysts consisting of human epidermis-like tissue. When the epidermal cells were injected alone or together with fibroblastic cells derived from human bone marrow, muscle fascia, or murine dermis, organized epidermoid cysts regressed within 6 weeks. In contrast, when the epidermal cells were injected together with human dermal fibroblasts, generated epidermoid cysts were maintained in vivo for more than 24 weeks. Histological examination showed that the reorganized epidermis, after injection of both epidermal keratinocytes and dermal fibroblasts, retained normal structures of the original epidermis during 6 to 24 weeks after transplantation. The results indicate that human dermal fibroblasts facilitate the long-term maintenance of the reorganized epidermis after xenotransplantation of cultured human epidermal keratinocytes by supporting self renewal of the human epidermal tissue in vivo.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0878
    Keywords: Epithelial-mesenchymal interaction ; Human epidermal keratinocytes ; Human fibroblasts ; Xenotransplantation ; Mouse (BALB/c nu/scid)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We examined effects of fibroblasts of different origin on long-term maintenance of xenotransplanted human epidermal keratinocytes. A suspension of cultured epidermal cells, originating from adult human trunk skin, was injected into double mutant immunodeficient (BALB/c nu/scid) mice subcutaneously, with or without cultured fibroblastic cells of different origin. At one week after transplantation, the epidermal cells generated epidermoid cysts consisting of human epidermis-like tissue. When the epidermal cells were injected alone or together with fibroblastic cells derived from human bone marrow, muscle fascia, or murine dermis, organized epidermoid cysts regressed within 6 weeks. In contrast, when the epidermal cells were injected together with human dermal fibroblasts, generated epidermoid cysts were maintained in vivo for more than 24 weeks. Histological examination showed that the reorganized epidermis, after injection of both epidermal keratinocytes and dermal fibroblasts, retained normal structures of the original epidermis during 6 to 24 weeks after transplantation. The results indicate that human dermal fibroblasts facilitate the long-term maintenance of the reorganized epidermis after xenotransplantation of cultured human epidermal keratinocytes by supporting self renewal of the human epidermal tissue in vivo.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 124 (1985), S. 255-260 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: A factor, termed neutrophil alkaline phosphatase-inducing factor (NAP-IF), that has the capacity to increase the NAP activity of granulocytes was characterized by using two samples: cystic fluid (CF) and conditioned medium of a tumor cell line (T3M5). The molecular weight of NAP-IF was shown to be between 13,000 and 45,000, and its isoelectric point was between 5.5 and 6.2. It was sensitive to heat and proteolytic enzymes, but was resistant to DNase and RNase, suggesting that NAP-IF is an acidic protein or glycoprotein. These characteristics of NAP-IF seem to be similar to those of granulocyte-macrophage colony-stimulating factor (GM-CSF) that is also present in the CF. NAP-IF rich fractions obtained by isoelectric focusing from CF were also found to be rich in a subclass of GM-CSF: granulocyte-CSF (G-CSF). Furthermore, a high correlation was noted between the activities of G-CSF and NAP-IF (γ = 0.798, P 〈 0.005). These results suggest that the two activities, i.e., G-CSF and NAP-IF, may be attributable to an identical macromolecule.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
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