Abstract: Pharmaceutical compositions comprising known verotoxins, particularly, verotoxin 1, have been found to be useful in the treatment of mammalian neoplasia, particularly, ovarian cancer and skin cancer. Surprisingly, although verotoxin 1 has previously been shown to have anti-neoplastic activity in vitro, non-lethal doses of verotoxin 1 have been shown to be therapeutically anti-neoplastic in vivo.

Abstract: Pharmaceutical compositions comprising known verotoxins, particularly, verotoxin 1, have been found to be useful in the treatment of mammalian neoplasia, particularly, ovarian cancer and skin cancer. Surprisingly, although verotoxin 1 has previously been shown to have anti-neoplastic activity in vitro, non-lethal doses of verotoxin 1 have been shown to be therapeutically anti-neoplastic in vivo.

Abstract: Pharmaceutical compositions comprising known verotoxins, particularly, verotoxin 1, have been found to be useful in the treatment of mammalian neoplasia, particularly, ovarian cancer and skin cancer. Surprisingly, although verotoxin 1 has previously been shown to have anti-neoplastic activity in vitro, non-lethal doses of verotoxin 1 have been shown to be therapeutically anti-neoplastic in vivo.

Abstract: A mammal lacking expression of particular CD45 isoform in certain cells of the immune system is provided. The mammal may optionally contain a transgene encoding the CD45RO isoform. Also provided are methods of using these mammals.

Abstract: The present invention provides N-terminal truncated transmembrane sensor histidine kinases that retain their ability to be autophosphorylated and/or their related histidine kinase activity. The N-terminal truncated transmembrane sensor histidine kinases are useful for obtaining detailed three-dimensional structural data of the catalytic portion of the protein. The three-dimensional structural data is included as part of the invention. In addition, the present invention provides methodology for related structure based rational drug design using the three-dimensional data. Nucleotide and amino acid sequences of the N-terminal truncated transmembrane sensor histidine kinases are also provided.

Abstract: The present invention provides N-terminal truncated transmembrane sensor histidine kinases that retain their ability to be autophophorylated and/or their related histidine kinase activity. The N-terminal truncated transmembrane sensor histidine kinases are useful for obtaining detailed three-dimensional structural data of the catalytic portion of the protein. The three-dimensional structural data is included as part of the invention. In addition, the present invention provides methodology for related structure based rational drug design using the three-dimensional data. Nucleotide and amino acid sequences of the N-terminal truncated transmembrane sensor histidine kinases are also provided.

Abstract: A method for the selective purging ex vivo of CD77 positive cells from bone marrow prior to autologous transplantation is described. The method involves treating the bone marrow with shiga toxin or shiga-like toxin-1 to kill CD77.sup.+ cells or to remove them by affinity chromatography. The toxin selectively binds to CD77.sup.+ cells and not to other bone marrow cells. The method offers a means for curing non-Hodgkin's lymphomas.

Abstract: Interferon regulatory factor-1 (IRF-1) is implicated in the regulation of type I interferons (IFN) and cell growth. The invention is a mutant mouse lacking expression of the IRF-1 gene. Mice lacking IRF-1 did not differ from normal mice in size, behaviour, or reproductive ability. With fibroblasts derived from these mutant mice, it was shown that type I IFN induction is dramatically reduced when cells are induced by poly(I):poly(C). In contrast, no differences were found when cells are induced by New Castle Disease Virus (NDV), or induced by poly(I):poly(C) with prior treatment of IFN-.beta.. On the other hand, the induction levels of IFN-inducible genes such as MHC class I and 2'-5' oligoadenylate synthetase (2'5'OAS) were not affected. Collectively, these results illustrate an IRF-1 independent mechanism of gene induction for type I IFN and these IFN-inducible genes. The critical role of IRF-1 in the immune system has been documented for the first time by the observation that the number of TcR.alpha..beta..

Abstract: A mutant mouse strain without CD4 expression has been generated by disrupting the CD4 gene using embryonic stem cell technology. In these mice CD4.sup.+ T lymphocytes are not present in peripheral lymphoid organs, but the development of CD8.sup.+ T cells and myeloid components is unaltered, indicating that expression of CD4.sup.+ on progenitor cells and CD4.sup.+ CD8.sup.+ (double positive) thymocytes is not obligatory. These mice have markedly decreased helper cell activity for antibody responses, whereas cytotoxic T cell activity against viruses was within normal range of that generated by CD4.sup.+ mice. This differential requirement for CD4.sup.+ helper T cells has important implications for the understanding of the immune function in a variety of immune disorders, including AIDS, in which the CD4.sup.+ cells are reduced or absent.

Abstract: The multiple biological activities of tumor necrosis factor (TNF) are mediated by two distinct cell surface receptors of 55 and 75 kDa. Mutant mice of the invention lacking tumor necrosis factor receptor (TNFR) p55 still express functional TNFRp75 molecules at the cell surface. Normal weight and size of the mutant mice are not altered. Thymocyte development and lymphocyte populations are normal, and clonal deletion of potentially self-reactive T cells is not impaired. Activation of the nuclear transcription factor .kappa.B (NF-.kappa.B), however, is completely abrogated after stimulation with TNF. Moreover, TNFRp55 mutant mice are protected from septic shock induced by bacterial endotoxin or superantigen, but Listeria clearance is severely impaired and mutant mice easily succumb to Listeria infection. Thus, the two TNF receptors are not redundant, are independently controlled, and play different roles in normal and pathological physiology.

Abstract: The invention is a branched synthetic peptide conjugate which can be designed to bind to a target cell surface receptor, to penetrate into target cells, and to deliver a diagnostic probe or cytotoxic functionality to a desired site of action. The invention provides a relatively small molecule of flexible design having a branched structure for systematically incorporating a desired number of cytotoxic functions, peptide-based localization signals or diagnostic probes. The invention addresses problems associated with protein-based therapeutic or diagnostic agents.

Abstract: The transcription factors, IRF-1 and IRF-2 are induced by interferons (IFNs) and a variety of other cytokines. IRF-1 functions as an activator whereas IRF-2 represses IRF-1 action by competing for binding to the same cis-elements. Recently, it has been shown that balanced expression between these two factors is critical for maintaining normal restraints on cell growth. Mutant mice deficient for IRF-2 were prepared by homologous recombination. In mutant cells, infection by Newcastle disease virus (NDV) resulted in the induction of type I IFN (IFN-.alpha. and IFN-.beta.) mRNAs, the levels of which were significantly higher than in wild type cells; whereas, such a difference was not found upon induction by poly(I):poly(C). Unlike the IRF-1 deficient mutant mice, the IRF-2 deficient mice of the invention exhibit multiple phenotypes of physical vulnerability, including lethality to lymphocytic choriomeningitis virus (LCMV).

Abstract: A mutant non-human mammal lacking expression of the lymphocyte-specific tyrosine kinase p56.sup.lck. Lck deficient mice possess few peripheral T lymphocytes and a pronounced thymic atrophy. The remaining thymus contains immature thymocytes surrounded by a perturbed thymic microenvironment. p56.sup.lck appears to play a crucial role in early thymocyte differentiation.

Abstract: Mice lacking expression of CD28 or particular CD45 isoforms in certain cells of the immune system are provided. Also provided are methods of using these mice.

Abstract: Mice lacking expression of CD28 or particular CD45 isoforms in certain cells of the immune system are provided. Also provided are methods of using these mice.

Abstract: A mouse lacking expression of a subunit of the IL-2 receptor in certain cells of the immune system is provided. Also provided are methods of using such mice.

Abstract: A mutant mouse strain without CD8 (Lyt-2 and Lyt-3) expression on the cell surface has been generated by disrupting the Lyt-2 gene using embryonic stem cell technology. In these mammals, for example, mice, CD8.sup.+ T lymphocytes are not present in peripherial lymphoid organs, but the CD4.sup.+ T lymphocyte population seems to be unaltered. Cytotoxic response of T lymphocytes from these mice against alloantigens and viral antigens is dramatically decreased. Proliferative response against alloantigens and in vivo help to B lymphocytes, however, are not effected. These mice should be useful for drug development and for studies of diseases of the immune system such as, autoimmunity, immunodeficiency, transplant rejection and tumor rejection.

Abstract: An immunoassay method for determining the specificity of binding of a monoclonal antibody to an antigen is afforded by comparing the binding of antibody and antigen both with and without the addition of excess epitope specific peptide.

Abstract: The preparation and use of polynucleotides and polypeptides corresponding to a novel gene expressed in fetal intestinal endoderm cells and the corresponding gene product, respectively, are disclosed. Expression of the gene, designated the intestinal oncofetal gene, is associated with neoplastic transformation in non-fetal intestinal cells other than adult crypt cells.Clone OCI-5 was deposited at the American Type Culture Collection, 12301 Parklawn Drive, Rocksville, Maryland 20852, U.S.A., on Aug. 18, 1988, and granted accession No. 40481.

Abstract: The invention provides a nucleic acid having a sequence which encodes a polypeptide that is at least part of a T cell antigen receptor. This encoded sequence is about 936 nucleotides in length and preferably is a human T cell antigen receptor. The nucleic acid sequence of one embodiment of the invention is shown in FIG. 3.The nucleic acid sequence may be used as a probe to determine whether an unknown cell, e.g., a tumor cell, is a T cell.Polypeptides encoded by the nucleic acid sequence include about 312 amino acids and are at least part of a T cell antigen receptor. They include at least one sequence which over 21 contiguous amino acids has greater than about 35% homology with mouse and human immunoglobin .lambda. light chains.Antibody to the polypeptide may be prepared and used to identify T cell antigen receptor and to determine whether an unknown cell, e.g., a tumor cell, is a T cell.