Showing papers by "Hilary Koprowski published in 1985"

Multiple sclerosis and human T-cell lymphotropic retroviruses.

Abstract: A combination of different types of data suggests that some multiple sclerosis patients respond immunologically to, and have cerebrospinal T cells containing, a retrovirus that is related to, but distinct from, the three types of human T-cell lymphotropic viruses. The role of this virus in multiple sclerosis is uncertain.

Expression of the receptor for epidermal growth factor correlates with increased dosage of chromosome 7 in malignant melanoma.

Abstract: Epidermal growth factor (EGF) receptor is expressed selectively by human melanoma cells which show the presence of an extra copy of chromosome 7. None of the cells of benign pigmented lesions (nevi) or radial growth phase (nonmetastatic) primary melanoma expressed EGF receptor and none of these cells showed an extra copy of chromosome 7. The results indicate that a single extra dose of a gene (for EGF receptor) may provide a selective advantage to cells in the late stages of tumorigenesis.

Rabies in the Tropics

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Normal salivary mucin contains the gastrointestinal cancer-associated antigen detected by monoclonal antibody 19-9 in the serum mucin of patients.

Abstract: Monoclonal antibody 19-9 produced by a hybridoma prepared from spleen cells of a mouse immunized with a human colon carcinoma cell line, detects an antigen in sera from many patients with gastrointestinal and pancreatic cancer. This antibody is directed against a carbohydrate with the sugar sequence (Formula: see text) In many gastrointestinal and pancreatic cancers this sequence occurs in a monosialoganglioside containing a sialylated Lea-active pentasaccharide (sialylated lacto-N-fucopentaose II, IV3-alpha-NeuNAc-III4-alpha-Fuc-LcOse4). In the sera of cancer patients the antigen occurs as a mucin. The antigen is also found in salivary mucin from many normal individuals belonging to the Le(a+b-) or Le(a-b+) blood group but not in salivary mucin from normal individuals belonging to the Le(a-b-) blood group. There is more antigen in mucin from individuals belonging to the Le(a+b-) blood group than in mucin from individuals belonging to the Le(a-b+) blood group.

Monoclonal antibody-dependent murine macrophage-mediated cytotoxicity against human tumors is stimulated by lentinan

Abstract: The beta (1----3) glucan lentinan was tested for its capacity to increase the cytotoxic effect of murine peritoneal macrophages for human tumor cells in the presence of monoclonal antibodies (MAbs). Activity was maximum in macrophages obtained on day 5 following intraperitoneal injection of CBA mice with 2.5 mg of lentinan per kg body weight. Macrophages stimulated by lentinan were cytotoxic in conjunction with IgG1, IgG2a and IgG3 MAbs, but not with IgG2b, IgM, or IgA MAbs. The demonstration of a similar enhancing effect by lentinan on human macrophages might have implications for potentiating the tumoricidal effect of these macrophages in the presence of tumor antigen-specific MAbs.

Monoclonal antibody-dependent murine macrophage-mediated cytotoxicity against human tumors is stimulated by lentinan

Abstract: The beta (1----3) glucan lentinan was tested for its capacity to increase the cytotoxic effect of murine peritoneal macrophages for human tumor cells in the presence of monoclonal antibodies (MAbs) Activity was maximum in macrophages obtained on day 5 following intraperitoneal injection of CBA mice with 25 mg of lentinan per kg body weight Macrophages stimulated by lentinan were cytotoxic in conjunction with IgG1, IgG2a and IgG3 MAbs, but not with IgG2b, IgM, or IgA MAbs The demonstration of a similar enhancing effect by lentinan on human macrophages might have implications for potentiating the tumoricidal effect of these macrophages in the presence of tumor antigen-specific MAbs

Gastrointestinal carcinoma-associated antigen detected by a monoclonal antibody in dysplasia and adenocarcinoma associated with chronic ulcerative colitis.

Abstract: Colorectal tissue specimens from 13 patients with chronic ulcerative colitis, of whom all had epithelial dysplasia and 2 had adenocarcinoma, were tested for the presence of gastrointestinal carcinoma-associated antigen (GICA), using an immunoperoxidase technique with a monoclonal antibody (MAb) against this antigen. GICA was present in the formaldehyde-fixed and paraffin-embedded sections of dysplastic and cancer tissue but absent from normal or hyperplastic epithelium. However, the pattern and extent of staining with the antibody did not correlate with the degree of dysplasia, i.e., "mild" dysplasia was often positive, and "severe" dysplasia was sometimes negative. Changes classified as "indefinite for dysplasia but probably negative" were variable in their expression of GICA. The adenocarcinomas were selectively labelled within cell clusters. In contrast, ulcerative colitis (UC) patients with severe inflammatory changes but with no detectable dysplasia were negative for GICA. GICA could be eluted from paraffin blocks of dysplastic tissue and biochemically characterized as a glycolipid. The detection of this antigen might be a useful complement to morphological examination in discriminating between precancerous and benign epithelial lesions of the colon.

Pharmacokinetic study of radiolabeled anti-colorectal carcinoma monoclonal antibodies in tumor-bearing nude mice.

Abstract: Monoclonal antibodies (MoAbs) 17-1A and 19-9, which specifically bind human colorectal carcinoma (CRC) cells, were tested for their usefulness in localizing colorectal tumors in nude mice. One of the 131I-labeled MoAbs and an irrelevant 125I-labeled immunoglobulin of the same isotype were injected into nude mice simultaneously bearing a human CRC and a human melanoma. The percentage of the injected dose of antibody per gram of tissue, the CRC/tissue ratios of antibody distribution, and the localization indices were calculated at various time intervals (2 h to 9 days). For both MoAbs, labeling to a specific activity of 10 μCi/μg by the iodogen method gave optimum immunoreactivity. The accumulation of MoAb 17-1A in CRC reached its maximum at 5 days and remained at this level for up to 9 days postinjection. For MoAb 19-9, which detects a circulating antigen shed by the tumor into the serum, the accumulation in the CRC was maximum at 24 h, and decreased thereafter. The CRC/organ ratios and localization indices for both MoAbs increased with time in the CRC tissue, but remained low and unchanged in the melanoma and normal tissues. Using F(ab′)2 antibody fragments, faster kinetics with earlier maximum accumulation, higher tumor/organ ratios, and better localization indices were achieved than with intact MoAbs. The data obtained was useful in defining parameters which must be considered before radiolabeled MoAbs are used in cancer patients for diagnostic purposes.

Rabies Virus Pathogenicity

Abstract: Cell-mediated immunity plays a major role in pathogenicity of rabies virus infection, and is probably also involved in the mechanism of post-exposure rabies prophylaxis. Live-attenuated rabies virus vaccines (ERA, HEP, Kelev) induce a strong cytotoxic T lymphocyte (CTL)-mediated response following i.c. inoculation. This reaction is a result of virus replication, since it is not dose-dependent. Similar levels of CTL response are generated by a wide range of virus dilutions. Conversely, infection with pathogenic rabies viruses does not result in generation of CTL and induces a total suppression of this T cell subpopulation. Other immune reactions and induction of interferon production are the same in animals infected with pathogenic and non-pathogenic viruses.