Abstract: This invention provides a novel murine cultured cell line which is derived from primary mouse embryo fibroblasts and which exhibits inducer-regulated growth kinetics. The cell line has the potential to grow either linearly or exponentially depending on exposure to an appropriate inducing agent. A corresponding cell line that does not respond to the inducing agent is also provided. The paired cell line system provides a valuable research tool for the development of therapeutic agents that target cells exhibiting deregulated growth kinetics, and also enables the identification of potential carcinogenic agents that alter stem cell renewal kinetics.

Abstract: Novel cell lines and methods are provided for inducibly expressing the Hepatitis B virus (HBV) genome within cultured cells. Cells are stably transformed with an HBV genome under control of an operator/promoter target sequence which can activate expression of the HBV genome when bound by a cognate transactivator protein. The cell lines are also stably transformed with a gene that encodes and expresses a suitable transactivator protein. Cells may be maintained under non-inducing conditions whereby the transactivator protein is unable to interact with the operator/promoter target sequence, so the HBV genome is not expressed. Under appropriate inducing conditions, the transactivator protein is enabled to interact with the operator/promoter target sequence, thereby activating expression of the HBV genome. The inducible system provides an effective and rapid cell-based assay to screen compounds for anti-hepadnaviral activity.

Abstract: An isolated nucleic acid molecule is provided which encodes a mammalian signal mediator protein involved in regulation of cellular morphological alterations. The encoded protein comprises an amino-terminal SH3 domain, an internal domain containing several SH2 binding motifs, and a carboxy-terminal effector domain that can induce pseudohyphal budding in yeast. The invention also provides the novel signal mediator protein, and antibodies thereto. These biological molecules are useful as research tools and as diagnostic and therapeutic agents for the identification, detection and regulation of complex signaling events leading to morphological, potentially neoplastic, cellular changes.

Abstract: A transcription control element is provided for controlling gene expression in myogenic cells. The transcription control element comprises an isolated DNA segment having an enhancer activity in cultured cells and in non-cultured myogenic cells. The transcription control element is isolated from upstream regions of genes encoding bHLH myogenic regulatory proteins. Specifically, an enhancer element from the upstream region of human myoD and an enhancer element from the upstream region of a quail qmf1 are provided. These myoblast-specific transcription control elements are capable of significantly increasing the levels of gene expression in myogenic cells and are intended to be applied in gene therapy, using myoblast transfer and microinjection techniques, wherein myoblast-specific gene expression is desired or required.

Abstract: An isolated nucleic acid is provided which encodes a transiently-expressed kinetochore protein, CENP-F. Also provided are the purified polypeptide encoded by the nucleic acid sequence, and antibodies immunologically specific for the polypeptide. These biological molecules are useful as markers of cellular proliferation, particularly for the identification of cells in the G2 and M phases of the cell cycle. Methods are provided for using the nucleic acid, protein and antibodies for assessing cellular proliferation in biological fluids and tissue samples, and for detecting the presence of autoantibodies to the protein.

Abstract: The present invention relates to transgenic animal model systems for human cutaneous melanoma. It is based, at least in part, on the discovery that, in susceptible transgenic mice, accelerated formation of melanoma tumors occurred near the wound borders of skin grafts carrying the Tyr-SV40E transgene, indicating that factors present during wound healing facilitate the formation of cutaneous melanoma in susceptible tissue.

Abstract: Diagnostic blood lead assays using porphobilinogen synthase protein function as an indicator of physiological response to lead exposure and as an indicator of the time period of lead exposure are disclosed.

Abstract: Phorbine derivatives having high potency and light absorptivity in the 650 to 780 nanometer range are useful in cancer diagnosis and therapy, especially photodynamic therapy.

Abstract: A method is provided for specifically altering the nucleotide sequence of an RNA molecule. As performed in vitro the method comprises: (1) selecting a target sequence in an RNA molecule; (3) hybridizing the target sequence with a complementary nucleic acid, either DNA or RNA, thereby forming a double-stranded structure; (4) incubating the hybrid molecule with a cellular extract which contains components capable of specifically converting U to C in an RNA molecule, when the U is disposed within a double-stranded structure. Incubation of the hybrid molecule with cellular extracts comprising the RNA editing component results in a specific alteration of the nucleotide sequence of the RNA at the target sequence. The method of the invention may also be applied in vivo. Complementary nucleic acids are introduced into cells and hybridized to the target sequence to form a double-stranded structure.

Abstract: An enzymatically active composition of matter, comprising an extracellular combination of a substantially virus-free hepadnavirus polymerase gene product and an RNA template for hepadnavirus minus strand DNA synthesis, is provided. The composition possesses a DNA priming activity and a reverse transcriptase activity. The hepadnavirus polymerase gene product is produced by in vitro expression of a hepadnavirus pol gene.The enzymatically active composition of matter is used in rapid in vitro assays to screen potential anti-hepadnaviral agents. Assays for various functions of the hepadnavirus DNA polymerase are provided, including: (1) binding of the polymerase gene product to hepadnavirus pre-genomic RNA; (2) DNA priming activity of the polymerase gene product; and (3) reverse transcriptase activity of the polymerase gene product.

Abstract: An enzymatically active, substantially virus-free hepadnavirus polymerase gene product is provided, which possesses a DNA priming function and reverse transcriptase activity, both of which are dependent on the presence of an RNA template and magnesium ions. The hepadnavirus polymerase gene product is produced by in vitro transcription and translation of a hepadnavirus pol gene.The enzymatically active hepadnavirus polymerase gene product is used in rapid in vitro assays to screen potential anti-hepadnaviral agents. An assay for the DNA priming activity of the gene product is provided, wherein covalent attachment of labelled dGTP to the gene product is quantitatively measured. An assay for the reverse transcriptase activity of the gene product is provided, wherein incorporation of nucleotide triphosphates into the nascent DNA minus strand is measured, taking advantage of the covalent attachment of said nascent strand to the polymerase gene product.

Abstract: Concentrations of one or more carbohydrates phosphorylated at a secondary hydroxyl, including fructose-3-phosphate and sorbitol-3-phosphate, in biological tissue or cells of diabetic patients are determined by .sup.31 P NMR Spectroscopy, High Performance Liquid Chromatography (HPLC) or other appropriate analytical techniques. Elevated levels of such phosphorylated carbohydrates, relative to a prescribed standard or threshold level, are associated with an increased risk for developing the degenerative complications of diabetes. A method is provided for determining the relative concentrations of such phosphorylated carbohydrates, whereby the relative risk of a patient for the development of diabetic complications and the efficacy of therapeutic intervention in prevention of such complications may be assessed.

Abstract: An RF resonator mounted on a dielectric support is operated in quadrature at a selected NMR frequency. The resonator consists of four axially distributed high frequency ring current paths on the support and at least four high frequency current paths interconnect each pair of adjacent ring paths. In the preferred embodiment at least sixteen equally spaced parallel segments connect each ring pair and are aligned with one another. The ring segments between the parallel segments together with the parallel segments form loops. At least one discrete capacitor is placed in each outer current loop thereby interrupting the loop. However, this is done so that no inner loop is interrupted by a capacitor. By using quadrature input/output coupling, either inductive or capacitive, a co-rotating mode is excited in the two outer loops through the inner loops providing a highly uniform field across the resonator.

Abstract: A radio frequency volume resonator mounted on a generally cylindrical dielectric support can be operated in quadrature at one or more NMR frequencies. The resonator consists of four axially distributed high frequency ring current paths and a dielectric support, at least four high frequency current paths interconnect each pair of adjacent ring paths, at least one discrete capacitor is placed in each current loop but arranged so that none of the ring current paths is interrupted by a capacitor.

Abstract: A radio frequency volume resonator mounted on a dielectric support can be operated in quadrature at one or more NMR frequencies. The resonator consists of four axially distributed high frequency ring current paths on the dielectric support. At least four high frequency current paths interconnect each pair of adjacent ring paths. The ring segments with interconnecting segments form loops. At least one discrete capacitor is placed in each loop.

Abstract: Method of treating retrovirus infection by administering extract of Phyllanthus niruri.

Abstract: A pharmaceutical preparation comprising the methanol extractable components of Phyllanthus niruri L. is administered to patients suffering from hepatitis B virus infection in an amount effective for inhibiting the growth of said virus.