Abstract: A method of introducing at least one human cytochrome P450 into a non-human animal c ell in which corresponding endogenous P450 enzyme activities have been disabled, thus the method provides a way of using a non-human animal cell to make predictions regarding P450-mediated metabolism in a human. The present invention also provides transgenic non-human animals produced by the method of the invention and uses therefor, especially in assessing xenobiotic/drug metabolism and toxicity.

Abstract: The present invention concerns the discovery that proteins encoded by a family of vertebrate genes, termed here hedgehog-related genes, comprise morphogenic signals produced by embryonic patterning centers, and are involved in the formation of ordered spatial arrangements of differentiated tissues in vertebrates. The present invention makes available compositions and methods that can be utilized, for example to generate and/or maintain an array of different vertebrate tissue both in vitro and in vivo.

Abstract: The present invention concerns the discovery that proteins encoded by a family of vertebrate genes, termed here hedgehog-related genes, comprise morphogenic signals produced by embryonic patterning centers, and are involved in the formation of ordered spatial arrangements of differentiated tissues in vertebrates. The present invention makes available compositions and methods that can be utilized, for example to generate and/or maintain an array of different vertebrate tissue both in vitro and in vivo.

Abstract: The present invention concerns the discovery that proteins encoded by a family of vertebrate genes, termed here hedgehog-related genes, comprise morphogenic signals produced by embryonic patterning centers, and are involved in the formation of ordered spatial arrangements of differentiated tissues in vertebrates. The present invention makes available compositions and methods that can be utilized, for example to generate and/or maintain an array of different vertebrate tissue both in vitro and in vivo.

Abstract: A gene encoding a polypeptide, related in sequence to retinoblastoma binding proteins 1 and 2, which is expressed in breast cancer, therapeutic and diagnostic methods relating to this gene and polypeptide.

Abstract: A conjugate compound comprises a cell-specific portion, such as an antibody specific to tumour cell antigens, and an enzymatically active portion which will cleave a cyanogenic compound to release cyanide. Enzymes such as &bgr;-glucosidases are suitable. The cyanogenic compound, e.g. amygdalin or some other plant-derived saccharide, is administered after the conjugate. Intravesical (intra-bladder) administration is preferred (for bladder cancers) and forms a further aspect of the invention, whether the compound is cyanide-liberating (as above) or suitable for therapy or imaging in any other way.

Abstract: A method for determining the susceptibility of a patient to cancer comprising the steps (i) obtaining a sample containing nucleic acid derived from the patient; and (ii) contacting the said nucleic acid with a nucleic acid capable of selectively hybridising to the region of human chromosome 10 which region is bounded by DNA defined by the markers D10S541 and D10S215. A nucleic acid capable of selectively hybridising to the region of human chromosome 10 which region is bounded by DNA defined by the markers D10S541 and D10S215 provided that the nucleic acid is not any one of certain YACs, BACs, PACs or ESTs defined herein. Preferably the said nucleic acid is a prostate tumour suppressor gene.

Abstract: A method of analysing a nucleic acid by mass spectrometry comprising the steps of: (1) preparing a nucleic acid molecule comprising a negatively charged non-phosphate sugar-sugar linkage; (2) eliminating the charge from all, or up to all but ten, of the sugar-sugar linkages of the said nucleic acid molecule; (3) introducing the said nucleic acid molecule in which the charge has been wholly or partly eliminated as said into a mass spectrometer; and (4) determining the mass of the said nucleic acid molecule. Preferably, the nucleic acid has no or one charge. A method of preparing a nucleic acid molecule containing no or up to ten negative charges and no or up to ten positive charges comprising the steps of (1) synthesizing a nucleic acid with a phosphorothioate linkage or a phosphoroselenoate linkage between sugar residues, and (2) reacting the said nucleic acid with an alkylating agent so as to eliminate the charge on the said phosphorothioate linkage or said phosphoroselenoate linkage.

Abstract: Antigens are derived from the tandem repeat sequence of the core protein of a human polymorphic epithelial mucin. These antigens include a core protein epitope which is recognized by certain antibodies which also bind certain carcinoma antigens, but not fully processed HPEM glycoprotein as produced by the normal lactating human mammary gland.

Abstract: A nucleic acid construct comprising a promoter capable of directing expression in the suprabasal cells of the epidermis and means to cause expression of an integrin subunit in the suprabasal cells. Preferably the means to cause expression of an integrin subunit is an integrin subunit coding sequence. A transgenic animal which expresses an &agr; subunit and a &bgr; subunit of integrin in the suprabasal cells of the epidermis and methods for making the transgenic animals. At least some of the transgenic animals are useful models of human disease, especially psoriasis. A method of treating psoriasis comprising administering to the patient a compound which modulates integrin function.

Abstract: Nucleic acid fragments are described which can be used as probes for detecting one of the strands of the DNA tandem repeat sequence in the gene encoding the core protein of human polymorphic epithelial mucin, or incorporated into an expression vector to encode a portion of the mucin core protein to be used for immunization purposes.

Abstract: Polymorphisms at positions 100, 271, 281, 294, 408, 506 or 1432 of the cytochrome P450 enzyme bufuralol-1'-hydroxylase are indicative of the extensive metaboliser/poor metaboliser phenotypes and can be detected using known methods such as amplification of the DNA with the polymerase chain reaction, followed by digestion with a suitable restriction enzyme and analysis by gel electrophoresis. The EM/PM phenotype is relevant to calculating safe or effective drug doses for individuals.

Abstract: Fusion compounds comprising a target cell-specific portion fused to an oligomeric rival nuclease are disclosed. The inventive compounds are useful as anti-cancer agents. Methods of preparation and use of the inventive compounds are disclosed.

Abstract: A molecule which (i) binds human membrane-bound carcinoembryonic antigen, (ii) binds a hybrid polypeptide consisting of residues 1 to 314 of human biliary glycoprotein joined (N-C) to residues 490 to C-terminus of human carcino embryonic antigen, but (iii) does not bind to human biliary glycoprotein excluding an intact mouse monoclonal antibody comprising an IgG group IIA heavy chain and a kappa group V light chain wherein the sequence of the V.sub.H chain is QVKLQQSGPELKKPGETVKISCKASGYTFTVFGMNWVKQAPGKGLKWMGWIN-TKTGEATYVEEFKGRFAFSLE TSATTAYLQINNLKNEDTAKYFCARWDFYDYVEAMDYWGQGTTVTVSS, or wherein the sequence of the V.sub.H chain is as given immediately above but the first amino acid residue of the V.sub.H CDR1 is glutamine and in either case the sequence of the V.sub.L chain is GDIVMTQSQRFMSTSVGDRVSVTCKASQNVGTNVAWYQQKPGQSPKALIYSASYRYSGVPDRFTGSG-SGTDFT LTISNVQSEDLAEYFCHQYYTYPLFTFGSGTKLEMKR. Preferably the molecule is a monoclonal antibody.

Abstract: An adenovirus or adenovirus-like particle which has a modified binding specificity conferred by a binding moiety. The binding moiety is heterologous to the adenovirus and is incorporated as a fusion protein with the fiber protein. This allows the adenovirus or adenovirus-like particle to bind to a target cell which is not the natural host cell of the virus. The penton fiber is modified by the insertion or, deletion, or substitution of amino acid residues, that disrupt the host-cell binding function so that the adenovirus or adenovirous like particle does not bind the natural host cell.