Abstract: A method is provided for repopulating degenerated of immunetolerant mice which lack mature B and T lymphocytes with xenogenic mammalian hepatocytes, particularly primate hepatocytes to generate chimeric mice. In addition, a method of generating a human hepatitis virus-infected chimeric mouse is provided. A preferred xenogenic primate hepatocyte is derived from human, chimpanzee or baboon. These chimeric mice are useful in the investigation of host and viral mechanisms determining hepadnaviral persistence and hepatocarcinogenesis. Methods for monitoring the development of hepatitis and hepatocellular carcinoma as well as methods for testing and screening anti-viral and anti-cancer compounds with this model system are also provided.

Abstract: This invention provides for murine telomerase reverse transcriptase (mTERT) enzyme proteins and nucleic acids, including methods for isolating and expressing these nucleic acids and proteins, which have application to the control of cell proliferation and aging, including the control of age-related diseases, such as cancer.

Abstract: A composition which comprises an animal cell population which contains immature animal cells. The immature animal cells are characterized by expression of alpha-fetoprotein or lack of essential expression of alpha-fetoprotein and albumin, and at least a portion of said immature animal cells or at least a portion of the progeny of said immature animal cells is capable of differentiating into cells which express albumin. The cell population is cultured under conditions which result in expansion of the cells. Expansion of the cells may be achieved by culturing the cells in the presence of an extracellular matrix and liver stromal cells; and preferably in the presence of growth factors. Such cells may be used for liver transplantation, artificial livers, and for toxicology and pharmacology studies. Such cells may also be genetically engineered to express proteins or polypepetides of interest.

Abstract: Methods and compositions for transforming cells, resulting in efficient and stable site-specific integration of transgenes, are disclosed. Transformation is achieved by introducing into a cell an acceptor vector, preferably a retroviral vector, which integrates into the genome of the cell. The acceptor vector comprises two incompatible lox sequences, L1 and L2. A donor vector is then introduced into the cell comprising a transgene flanked by the same L1 and L2 sequences. Stable gene transfer is initiated by contacting the lox L1 and L2 sequences with Cre recombinase.

Abstract: Recombinant mycobacterial vaccine vehicles capable of expressing DNA of interest which encodes at least one protein antigen for at least one pathogen against which an immune response is desired and which can be incorporated into the mycobacteria or stably integrated into the mycobacterial genome. The vaccine vehicles are useful for administration to mammalian hosts for purposes of immunization. A recombinant vector which replicates in E. coli but not in mycobacteria is also disclosed. The recombinant vector includes 1) a mycobacterial gene or portions thereof, necessary for recombination with homologous sequences in the genome of mycobacteria transformed with the recombinant plasmid; 2) all or a portion of a gene which encodes a polypeptide or protein whose expression is desired in mycobacteria transformed with the recombinant plasmid; 3) DNA sequences necessary for replication and selection in E. coli; and 4) DNA sequences necessary for selection in mycobacteria (e.g., drug resistance).

Abstract: The present invention provides a purified and isolated nucleic acid encoding Rhodococcus L-phenylalanine dehydrogenase. The present invention also provides a vector comprising nucleic acid encoding Rhodoccus L-phenylalanine dehydrogenase, a host cell transformed with the vector, and a method for producing recombinant L-phenylalanine dehydrogenase.

Abstract: This invention relates to InhA enzyme crystals and to methods of growing said crystals. This invention is further directed to the utilization of said crystals to determine the three dimensional structure of InhA enzyme utilizing heavy atom derivatives of said crystals, and to the identification and development of compounds which inhibit the biochemical activity of InhA enzyme in bacteria and plants.

Abstract: The present invention provides a rep-max fusion gene which encodes a Rep-max protein capable of suppressing the oncogenic activity of a Myc family oncoprotein. The present invention further provides a vector containing nucleic acid encoding a Rep-max protein, a vector capable of expressing Rep-max protein and a recombinant viral vector capable of introducing nucleic acid encoding Rep-max protein into a target cell. Finally, the present invention provides a method for suppressing the oncogenic activity of Myc family oncoproteins in a tumor cell and for inhibiting the growth of a tumor in a subject.

Abstract: This invention is directed to a chimeric mouse capable of mounting murine cellular and humoral immune response, said chimeric mouse being tolerant of human tissue implanted therein. The chimeric mouse of this invention is capable of developing murine T cells and producing murine IgG antibodies, which T cells and antibodies are tolerant of the human tissue implanted in said mouse, thereby allowing for the challenge of said vaccinated mouse with human-specific pathogens and determining the capacity of the vaccine to protect the cells in said implanted tissue from infection. This invention is also directed to a method for the development of said chimeric mouse, as well as to the use of said chimeric mouse for the screening of vaccines for human-specific pathogens.

Abstract: The present invention provides a conditional shuttle phasmid constructed by inserting a cosmid into a non-essential region of the D29 mycobacteriophage which is capable of introducing DNA of interest into the chromosome of mycobacteria, especially M. tuberculosis complex organisms and other slow growing mycobacteria. The present invention provides a recombinant mycobacterium which expresses a DNA of interest incorporated into its chromosome by a conditional shuttle plasmid containing the DNA of interest. The present invention further provides a mycobacterial auxotrophic mutant and method of generating auxotrophic mutants. Finally, the present invention provides a method of inactivating a mycobacterial virulence gene.

Abstract: This invention relates to a method for selectively enhancing the analgesic potency of a bimodally-acting opioid agonist such as morphine and simultaneously attenuating anti-analgesia, hyperalgesia, hyperexcitability, physical dependence and/or tolerance effects associated with the administration of the bimodally-acting opioid agonist. The method of the present invention comprises administering to a subject an analgesic or sub-analgesic amount of a bimodally-acting opioid agonist such as morphine and an amount of an excitatory opioid receptor antagonist such as naltrexone or nalmefene effective to enhance the analgesic potency of the bimodally-acting opioid agonist and attenuate the anti-analgesia, hyperalgesia, hyperexcitability, physical dependence and/or tolerance effects of the bimodally-acting opioid agonist.

Abstract: This invention is directed to L5 shuttle phasmids capable of delivering foreign DNA into mycobacteria and to methods of producing L5 shuttle phasmids. In addition, this invention is directed to a method of generating mycobacterial mutations and to a method of producing mycobacterial vaccines.

Abstract: Inha enzyme crystals and methods of growing said crystals are presented. Three crystal forms of the Inha enzyme with discrete unit cell parameters were obtained. The crystals of the Inha enzyme are of sufficient size and quality for x-ray crystallographic determination of the three dimensional structure of the Inha enzyme in concert with heavy atom derivatives of said crystals. With the three dimensional structure of the Inha enzyme, compounds which inhibit the biochemical activity of the Inha enzyme may be developed.

Abstract: The present invention provides a compound having the structure: ##STR1## wherein R is a branched or unbranched C1-C30 alkyl or alkenyl; or a branched or unbranched C1-C30 alkyl or alkenyl substituted with S, O, N, P, SO.sub.2, F, C1, Br, or I, wherein S, O, N, P, or SO.sub.2 replaces at least one --CH.sub.2 --, and F, Cl, Br, or I replaces at least one H. The present invention also provides a pharmaceutical composition comprising the compound above, as well as a method for treating a mycobacterial disease or infection in a subject in need of such treatment by administering to the subject an effective amount of the compound above.

Abstract: This invention relates to the use of neuronotrophic factors, such as nerve growth factor (NGF), ciliary derived neuronotrophic factor (CNTF), brain derived neuronotrophic factor (BDNF), neuronotrophin-3 (NT-3), fibroblast growth factor (FGF), epidermal growth factor (EGF), transforming growth factor .varies. (TFG-.varies.), transforming growth factor .beta. (TGF-.beta.) and others to prevent drug-induced neuropathy.

Abstract: Based on the discovery that the human bilirubin/phenol UDP-glucuronosyltransferase ugt1 gene complex contains an electrophile responsive element and the knowledge that the rat NADP(H):quinone reductase gene contains an electrophile responsive element, agents which at a concentration of less than 50 .mu.M double the quinone reductase specific activity of Hepa 1clc7 cells, e.g., BHT and sulforaphane, are used for the prophylaxis or treatment of newborn jaundice.

Abstract: This invention relates to a method of preventing hyperalgesia and other undesirable side-effects associated with the administration of growth factor, including nerve growth factor, utilizing an antagonist capable of inactivating excitatory opioid receptor-mediated functions on neurons in the nociceptive pathway. In addition, this invention relates to a composition comprising a growth factor and an antagonist capable of inactivating excitatory opioid receptor-mediated functions on neurons in the nociceptive pathway.

Abstract: The present invention provides a class of compounds having the formula:Y--R--CH.sub.2 --CH.sub.2 --[O--CH.sub.2 --CH.sub.2 ].sub.n --R'--y'wherein n is an integer from about 5 to about 200; R is carbamate, urea, or amide; R' is carbamate, urea, amide, or oxygen; Y is 4-phenylmalemimido or 3-phenylmaleimido; and Y' is 4-phenylmalemimido, 3-phenylmaleimido, methyl or hydrogen. The present invention also provides various hemoglobin compositions modified with the class of compounds of the present invention, processes for preparing these compositions, as well as pharmaceutical compositions comprising these compositions.

Abstract: This invention relates to a method for selectively enhancing the analgesic potency of a bimodally-acting opioid agonist such as morphine and simultaneously attenuating anti-analgesia, hyperalgesia, hyperexcitability, physical dependence and/or tolerance effects associated with the administration of the bimodally-acting opioid agonist. The method of the present invention comprises administering to a subject an analgesic or sub-analgesic amount of a bimodally-acting opioid agonist such as morphine and an amount of an excitatory opioid receptor antagonist such as naltrexone or nalmefene effective to enhance the analgesic potency of the bimodally-acting opioid agonist and attenuate the anti-analgesia, hyperalgesia, hyperexcitability, physical dependence and/or tolerance effects of the bimodally-acting opioid agonist.

Abstract: A composition which comprises an animal cell population, and which contains immature animal cells. The immature animal cells are characterized by expression of alpha-fetoprotein or lack of essential expression of alpha-fetoprotein and albumin, and at least a portion of said immature animal cells or at least a portion of the progeny of said immature cells is capable of differentiating into cells which express albumin. The cell population is cultured under conditions which result in expansion of the cells. Expansion of the cells may be achieved by culturing the cells in the presence of an extracellular matrix and liver stromal cells; and preferably in the presence of growth factors. Such cells may be used for liver transplantation, artificial livers, and for toxicology and pharmacology studies. Such cells may also be genetically engineered to express proteins or polypeptides of interest.