A. we propose to develop a methodology by which the genes coding for disease-specific antigens can be rapidly cloned using recombinant dna techniques. the system lends itself to high level expression of these antigens as hybrid proteins, which facilitates production of antibodies to the antigens.… More

Testing its immunotherapeutic potential the long-term objective of this project is to develop processes for the production of b-cell growth factor (bcgf) and to test the potential applications of bcgf for the treatment of human immunopathological conditions. bcgf may be useful as an… More

The objective of this research plan is to isolate a cdna sequence encoding tumor necrosis factor (tnf) and, by manipulation of that sequence, to produce and secrete the mature tnf protein from the yeast saccharomyces cerevisiae. previous work on tnf has shown it to have cytostatic or cytolytic… More

Lymphotoxin is a lymphokine which has potent antitumor activity. it is a glycoprotein with a molecular weight of 25,000 daltons. due to the minute amount produced by lymphocytes, evaluation of its pharmaceutical potential requires that it be cloned and expressed in a suitable host. in order to… More

We promise to develop methods for the large-scale production of human colony stimulating factors (csf) from normal human peripheral blood lymphocytes. the fermentation methods employed will be similar to those used for the production of natural interleukin-2. we are producing human il-2 for clinical… More

We propose to develop a methodology by which the genes coding for autoimmune disease-specific protein antigens can be rapidly cloned using recombinant dna techniques. the system which we are using lends itself to high-level expression of these antigens as hybrid proteins in e. coli. this facilitates… More

We propose to identify the genes for autoimmune disease-specific protein antigens by the use of recombinant dna techniques. the system that we are using lends itself to high-level expression of these antigens as hybrid proteins in e. coli. this approach facilitates production of these antigens for… More

Experience with the cloning and expression of cloned genes in saccharomyces cerevisiae suggests that the recovered yield of correctly folded protein product is greatly improved by the use of a yeast-secretion process. this is especially true for proteins that are normally secreted fromtheir natural… More

We propose to use the gene for alpha-1-anti-trypsin (1-at), a moderately glycosylated human serum protein, as a specific model to test the feasibility of using bakers' yeast (s. cerevisiae) as a host microorganism for production of human glycoproteins with pharmaceutical applications. specifically,… More

This project addresses the need for efficient methods to rapidly determine the dna sequence of yeast artificial chromosome (yac) or cosmid clones without subcloning small fragments. the method combines multiplex dna sequencing with ligase-mediated polymerase chain reaction (pcr) amplification of… More

Urokinase-type plasminogen activator (upa) is a thrombolyticprotease that has been implicated in certain nonthrombolyticphysiological processes, most notably the invasive growth or migration of metastatic cells and of macrophages. the role of upa in cell migration appears to involve binding of this… More

Genetic engineering techniques will be used to enable yeast cells to produce functional monoclonal antibody fragments. the long-term applications are: (1) reliable production of kilogram quantities of monoclonal antibodies (needed in cancer therapy and diagnostic imaging) from yeast fermentations… More

Highly polymorphic alu loci will be used as genetic markers to refine the human genetic linkage map. a refined genetic map is important for mapping inherited disease genes, for studying loss of heterozygosity, and for constructing a physical map of the human genome. regions flanking alu elements… More

A method of dna typing using the polymerase chain reaction (pcr) will be developed, as well as a collection of pcr primers that will amplify specific vntr regions of human dna. conditions will be optimized to enable visualization of the resulting dna fragments on a polyacrylamide gel. by using… More

The long-term objective is to develop a reliable dna probe test for the prediction of the debrisoquine metabolism phenotype. the specific aims are to: (1) develop methods for probing the cyp2d6 locus encoding debrisoquine hydroxylase independently of the highly homologous but unexpressed cyp2d7 and… More

Human rflp probes which have been genetically mapped will be converted into pcr-based markers. mapped rflp probes are an important tool for research in many areas. a subset of about 150 rflp probes has been selected and is currently being used for mapping genetic disease genes and studying loss of… More

The aim of this project is to demonstrate a new multiplex dna diagnostic test which can simultaneously detect nucleotide differences between several different alleles at several different genetic loci in a single test sample of human dna. the test portion of the protocol relies on allele-specific… More

The objective of this proposal is to develop and distribute a set of mapping panels for all human autosomes and the X chromosome. These mapping panels, consisting of 300-400 highly polymorphic loci spaced at 10-15 centiMorgan (cM) intervals, will provide the necessary tools for an efficient, and… More

We will develop a general purpose sequence assembly algorithm and corresponding software to be used by large scale sequencing projects. We will incorporate many features of existing assembly programs into our software. Some of these features include sensitive overlap detection, robust detection of… More

Assays based on dna hybridization are very commonly used in molecular biology, clinical diagnostics, and the human genome project. however, efficiency and sensitivity of hybridizatins are often limited by non-specific binding of probe molecules or detection system components to the target dna or… More

Our goal is to identify genes that play a critical role in the development of prostate cancer. Thespecific aim of Phase I is to use differential display (Liang and Pardee, 1992) to identify differentiallyexpressed genes in normal prostate and tumorigenic prostate cell lines. Differentially amplified… More

We will develop a rapid, cost-effective screening method for detecting all mutations in the p53gene. The goal of Phase I is to optimize conditions for direct genomic sequencing of PCR products fromhuman tumor cell lines. Both malignant mesotheliomas and sarcomas have been shown to be inducedby… More

DESCRIPTION (provided by applicant): In 1990, there were over 1.69 million noninstitutionalized walker users in the United States (85% over the age of 65 years). A walker is used to provide support, reduce weight bearing on the lower limbs, and therefore to minimize the likelihood of falls. There… More

DESCRIPTION (provided by applicant): A major challenge facing the rehabilitation field is to understand the relationship(s) between physical impairments, functional limitations and disabilities. Functional movement analysis is a key to unlocking these secrets. C-Motion's Visual3D clinical movement… More

DESCRIPTION (provided by applicant): The goal of this project is to develop an open source, commercially supported software package to assist the neuroscience research community in performing analyses of neurophysiological and psychophysical data, which makes these analyses available for clinical… More

DESCRIPTION (provided by applicant): A major challenge facing the rehabilitation field is measuring and predicting improvements of people with physical impairments, functional limitations and disabilities. Functional movement analysis is a key to unlocking these secrets. C-Motion's Visual3D… More

DESCRIPTION (provided by applicant): In recent years, the field of neurological rehabilitation has been reinvigorated with the finding that the central nervous system retains plasticity even into adulthood. Interventions utilizing massed practice neurorehabilitation provide a setting in which an… More