Abstract: The present invention comprises compositions and preparations for the promotion of wound healing in an animal. Methods for preparing the compositions as well as methods for using the compositions to achieve the promotion of wound healing, are also provided. The composition may comprise a dietary regimen or a therapeutic agent. These compositions include a wound healing promoting concentration of nucleotides. By way of example, such nucleotides may comprise RNA, adenine, uracil or a mixture thereof. The compositions can be prepared as suitable for oral, parenteral, intravenous or topical administration. Methods for using the preparation as a treatment to enhance the healing of an already existing wound or for use as a pretreatment regimen for animals in anticipation of surgery, are also disclosed.

Abstract: A variety of genetic constructs are disclosed that will find both in vitro and in vivo use in the area of tumor biology and cancer therapy. In particular, expression constructs are provided that contain a p16 encoding region and other regulatory elements necessary for the expression of a p16 transcript. One version of the expression construct is a replication-deficient adenoviral vector. Also provided are methods for the transformation of cell lines and the inhibition of cancer cell proliferation.

Abstract: The present invention provides animals and methods for the evaluation of vaccines. In particular, the present invention provides humanized animal models for the evaluation of vaccines designed to confer immunity against human pathogens, including vaccines directed against the human immunodeficiency virus. The present invention further relates to HIV vaccines. In particular, the present invention provides attenuated replication-competent HIV vaccines and replication-defective HIV vaccines. In addition, the invention provides modified Leishmania cells expressing HIV proteins.

Abstract: The present invention describes the identification, isolation, cloning, and sequencing of the Alzheimer Related Membrane Protein (ARMP) gene for both normal and mutant forms. An analogous mouse gene, mARMP gene, has also been isolated, cloned, and sequenced. The gene transcript and gene products are used in developing DNA diagnosis for and detection of carriers of the gene, Alzheimer's Disease diagnosis, gene therapy, protein therapy, immunotherapy, as well as the isolation and manufacture of the protein and the development of transgenic animals carrying mutations in the ARMP gene.

Abstract: Methods of killing neoplastic cells are provided. The invention relates to the use of NADPH-cytochrome P450 reductase (RED) gene transfer in combination with cytochrome P450 gene transfer to enhance the sensitivity of tumor cells to anti-cancer drugs that are activated by P450 enzymes. The use of bioreductive drugs that are activated by RED and/or cytochrome P450, in this paradigm, is also provided.

Abstract: An isolated nucleic acid molecule that hybridizes under stringent conditions, or shares at least 80% sequence identity, with a defined genomic region upstream of the coding region of a FSH&bgr; gene, and a DNA construct containing that nucleic acid molecule as a targeting sequence for homologous recombination.

Abstract: By transducing cells with an HIV-1-MN molecular clone deleted in the major packaging sequence, a stable HIV-1 packaging cell line, &psgr;422 was produced. &psgr;422 cells form syncytia with CD4 positive cells, correctly express HIV-1 structural proteins, and produce large amount of mature particles with normal RT activity. These particles are not infectious. When stably transfected with an HIV-based retroviral vector, the &psgr;422 cell line produces hybrid virions capable of transducing CD4 positive cells with high efficiency (e.g., 105 cells/ml). The availability of this stable, noninfectious HIV-1 packaging cell line capable of generating high titer HIV vectors enables the use of HIV-1 based nucleic acids delivery systems, for example, in gene therapy. An HIV-2 based vector is packaged by the packaging cell lines, demonstrating that HIV-2 cell transformation vectors are packaged by the packaging cell line.

Abstract: A method for activating a mammalian immune system entails a series of IL-2 administrations that are effected intermittently over an extended period. Each administration of IL-2 is sufficient to allow spontaneous DNA synthesis in peripheral blood or lymph node cells of the patient to increase and peak, and each subsequent administration follows the preceding administration in the series by a period of time that is sufficient to allow IL-2 receptor expression in peripheral or lymph node blood of the patient to increase, peak and then decrease to 50% of peak value. This intermittent IL-2 therapy can be combined with another therapy which targets a specific disease state, such as an anti-retroviral therapy comprising, for example, the administration of AZT, ddI or interferon alpha. In addition, IL-2 administration can be employed to facilitate in situ transduction of T cells in the context of gene therapy.

Abstract: Several genes encoding subunits of the neuronal nicotinic acetylcholine receptors have been cloned and regulatory elements involved in the transcription of the &agr;:2 and &agr;:7-subunit genes have been described. Yet, the detailed mechanisms governing the neuron-specific transcription and the spatio-temporal expression pattern of these genes remain largely uninvestigated. The &bgr;2-subunit is the most widely expressed neuronal nicotinic receptors subunit in the nervous system. We have studied the structural and regulatory properties of the 5′ sequence of this gene. A fragment of 1163 bp of upstream sequence is sufficient to drive the cell-specific transcription of a reporter gene in both transient transfection assays and in transgenic mice. Deletion analysis and site-directed mutagenesis of this promoter reveal two negative and one positive element. The positively acting sequence includes one functional E-box.

Abstract: MY1 polypeptides and polynucleotides and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing MY1 polypeptides and polynucleotides in the design of protocols for the treatment of infections such as bacterial, fungal, protozoan and viral infections, particularly infections caused by HIV-1 or HIV-2; pain; cancers; anorexia nervosa; bulimia; cachexia; obesity; diabetes; asthma; Parkinson's disease; acute heart failure; hypotension; hypertension; urinary retention; osteoporosis; angina pectoris; myocardial infarction; ulcers; asthma; allergies; benign prostatic hypertrophy; and psychotic and neurological disorders, including anxiety, schizophrenia, manic depression, delirium, dementia, severe mental retardation and dyskinesias, such as Huntington's disease or Gilles dela Tourett's syndrome, among others, and diagnostic assays for such conditions.

Abstract: Three novel alleles of the serotonin transporter gene are disclosed and shown to be effective markers for screening and diagnosis of migraine and psychiatric disorders. The sequences of the alleles are given. Methods for in vitro screening of individuals using DNA taken from blood samples are taught.

Abstract: Disclosed herein is the treatment of vision loss in a mammal by transplanting an effective amount of hNT-Neuron cells. The treatment can be accomplished by injecting the cells into the retinal area of the eye. Additionally, the cells can be injected into the visual cortex of the brain. Conditions to be treated are vision loss due to optic nerve damage, including glaucoma, optic nerve sheath meningioma and glioma, Graves' ophthalmopathy, benign or malignant orbital tumors, metastatic lesions, tumors arising from the adjacent paranasal sinuses or middle cranial fossa, giant pituitary adenomas, brain tumors or abscesses, cerebral trauma or hemorrhage, meningitis, arachnoidal adhesions, pseudotumor cerebri, cavernous sinus thrombosis, dural sinus thrombosis, encephalitis, space-occupying brain lesions, severe hypertensive disease or pulmonary emphysema.

Abstract: The present invention provides a method of human gene therapy using AAV vectors with essentially wildtype phenotype. Genes of 900 bases or less can be inserted into wildtype AAV and still allow the resulting vector to have a largely wildtype phenotype. For example, several antisense genes could be inserted and still allow packaging. Such wildtype vectors have several advantages. First, high titers of such vectors is easy to accomplish. Second, the vectors, since they include the Rep78 gene, integrate specifically into human chromosome 19. Third, such vectors, being wildtype, spread after their initial introduction. Another method for use of large wildtype AAV genomes is as complementors for fully defective AAV vectors. Such complementors can be delivered by virus infection and, be introduced easily into 100% of the cells used to produce virus. Viral infection is superior to synthetic techniques for introducing DNA into tissue culture producer cells.

Abstract: Methods of treatment or prevention of hyperproliferative diseases or pre-cancerous conditions affecting epithelial cells, such as psoriasis, vitiligo, atopic dermatitis, or hyperproliferative or UV-responsive dermatoses, hyperproliferative or allergically mediated diseases of other epithelia and methods for reducing photoaging or for prophylaxis against or reduction in the likelihood of the development of skin cancer, are disclosed.

Abstract: A transcribed non-naturally occuring RNA molecule comprising a desired RNA molecule, wherein the 3' region of the RNA is able to base-pair with at least 8 bases at the 5' terminus of the same RNA molecule.

Abstract: Retroviral vectors are disclosed which include an insertion site for genes of interest and are capable of expressing high levels of the protein derived from the genes of interest in a wide variety of transfected cell types. Also disclosed are retroviral vectors lacking a selectable marker, thus rendering them suitable for human gene therapy in the treatment of a variety of disease states without the co-expression of a marker product, such as an antibiotic. These retroviral vectors are especially suited for use in certain packaging cell lines.

Abstract: Nucleotide vector composition containing such vector and vaccine for immunization against hepatitis. Nucleotide vector comprising at least one gene or one complementary DNA coding for at least a portion of a virus, and a promoter providing for the expression of such gene in muscle cells. The gene may be the S gene of the hepatitis B virus. A nucleotide vector composition when administered to even chronic HBV carriers is capable of breaking T cell tolerance to the surface antigens of hepatitis B virus. A vaccine preparation containing said bare DNA is injected into the host previously treated with a substance capable of inducing a coagulating necrosis of the muscle fibers.

Abstract: This invention provides a method of regenerating a functional liver by transplantation of pancreas cells. Also provided are pancreas cell capable of regenerating functional liver tissue.

Abstract: The invention provides transgenic nonhuman mammals producing phosphorylated lysosomal proteins in their milk, and methods of generating the same. Phosphorylation occurs at the 6' position of a mannose side chain residue. Also provided are methods of purifying lysosomal proteins from milk, and incorporating the proteins into pharmaceutical compositions for use in enzyme replacement therapy.

Abstract: Disclosed herein are methods and compositions for identifying morphogen analogs. Preferred methods rest on the use of test cells comprising DNA defining a morphogen-responsive transcription activating element operatively associated with a reporter gene. In certain embodiments, the methods involve an osteogenic protein 1 (OP-1) responsive transcription activating element. Substances that activate the OP-1 responsive transcription activating element are considered herein likely to be useful for reproducing in vivo effects of morphogens such as OP-1.