NIH Invention Disclosures, Feb. 14, 1997
Text of invention disclosures forwarded by NIH on Feb. 14, 1997 for publication in the Federal Register
Methods and Compositions for Monitoring DNA Binding Molecules in Living Cells
Description of Invention:
This technology is directed to methods of detecting the binding of fluorescently labeled compounds to DNA by a direct, real time, visual detection and to the characterization/screening of ligands to ligand-dependent DNA-binding proteins. Using cell lines harboring multiple copies of a defined transcriptional regulatory unit, visualization system and assay have been developed to determine the effect of ligand in promoting binding of ligand-dependent DNA binding proteins to nuclear targets, including to a define transcriptional regulatory DNA sequence. Quantitative and qualitative analyses show that when this technology is applied to study the effect of ligand, such as antagonist RU486 and agonist dexamethasone, on the glucocorticoid receptor, agonist ligand induces a nuclear accumulation of the receptor in a dose-dependent manner that is strickingly different from an antagonist ligand. Furthermore, by taking advantage of a unique cell line designated 3134, which contains 200 copies of a promoter region each containing 4 copies of a specific DNA-binding sequence for the receptor in a tandem array thereby producing 1600 copies of the DNA binding region, the agonist-induced binding of the receptor to this array can be observed in living cells. This cell line and the related methods may prove to be an important aid in monitoring steroid administration to patients through the direct measurement of steroid activity from a blood sample. This method is also applicable for high throughput visual (quantitative and qualitative) screening of ligands to orphan receptors either agonist or antagonist, determining the effective dosage levels of agonist/antagonists on a real time basis, and to identify modifying chemical or biological agents that alter DNA-binding specificity in living cells.
Inventors:
H Htun and G Hager (NCI)
Patent Status:
OTT Reference No. E-021-96/0 filed 08 Dec 95 and
OTT Reference No. E-021-96/1 (CIP)
Foreign rights are available
Portfolios:
Internal Medicine - Diagnostics, anti-inflammatory
Internal Medicine - Diagnostics, imaging agents
Internal Medicine - Therapeutics
For additional information, please contact:
Stephen Finley, Ph.D.
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7735 ext. 215
Fax: 301/402-0220
The Use of Functional N-Methyl-D-Aspartate Antagonists to Ameliorate or Prevent Aminoglycoside-induced Ototoxicity
Description of Invention:
Aminoglycoside (AGS) antibiotics are extremely effective at treating bacterial infections such as sepsis, endocarditis, and tuberculosis, but are currently used in only 3% of all clinical admissions in the United States because of their tendency to induce ototoxicity. Approximately 30-40% of all patients who receive an AGS antibiotic will develop measurable and usually permanent hearing loss. A guinea pig model was used to test whether N-Methyl-D-Aspartate (NMDA) antagonists could prevent or reduce the severity of the hearing loss when AGS antibiotics were administered. For example, the NMDA antagonists, dizocilpine and ifenprodil, were tested with the AGS antibiotics, neomycin and kanamycin, and were found to prevent or lessen the hearing loss in over 98% of the animals tested. Over 75% of the tested animals maintained normal hearing levels. It is believed that the use of this method will allow physicians to readily administer aminoglycoside antibiotics without the fear of causing permanent hearing loss in the patient.
Inventors:
A Basile and P Skolnick (NIDDK)
Patent Status:
Serial No. 08/712,477 filed 11 Sep 96
Portfolio:
Internal Medicine - Therapeutics, other
For additional information, please contact:
Stephen Finley, Ph.D.
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7735 ext. 215
Fax: 301/402-0220
A Basal Cell Carcinoma Tumor Suppressor Gene
Description of Invention:
Novel human nucleic acid sequences and polypeptides derived from the tumor suppressor, PTC or patched gene which have been mapped to human chromosome 9q22.3-q31, have been discovered for use in cancer diagnosis and therapy. Mutations of this gene are associated with Nevoid Basal Cell Carcinoma Syndrome (NBCCS) a disease associated with skin cancer and human developmental defects such as Gorlin Syndrome comprising skeletal defects, craniofacial and brain abnormalities. Methods of detection of PTC in a tissue sample have been found as well as recombinant cells, antibodies, and pharmacological compositions useful in treatment of the disease. Methods of diagnosis of and therapy for NBCCS have also been found.
The PTC gene is thought to encode a protein which selectively switches off growth factor production in certain cells by interaction with members of the family of proteins encoded by the "hedgehog" gene, which instructs cells during development and growth. NBCCS is the result of abnormal PTC gene products that encode non-functional or functionally reduced NBCCS polypeptides. This lack of function may be caused by insertions, deletions, point mutations, splicing errors, premature termination codons, missing initiators, etc. The tumors caused by NBCCS are slow growing tumors that rarely metastasize, but which can cause significant morbidity and occasional mortality from local invasion.
Inventors:
M Dean et al. (NCI)
Patent Status:
Serial No. 60/017,906 filed 17 May 96
Portfolios:
Cancer - Diagnostics
Cancer - Therapeutics
Cancer - Research Materials
For additional information, please contact:
Ken Hemby
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7735, ext. 265
Fax: 301/402-0220
E-mail: jh259b@nih.gov
Process for Detecting Alzheimer's Disease Using Cultured Cells
Description of Invention:
A novel process has been developed for distinguishing between clinically normal individuals and those who have Alzheimer's disease (AD), a form of senile dementia that affects millions of Americans. This invention should aid considerably in the diagnosis of sporadic AD before signs and symptoms become fully apparent and will make it possible in familial AD to determine the presence or absence of AD gene(s) years before the patient becomes symptomatic. Previous studies of AD revealed that cells cultured from patients with familial or sporadic AD were hypersensitive to the lethal effects of ionizing radiation; however, none of these assays provided large enough differences between normal and AD cells to be useful in reliably distinguishing an AD patient from normal. The present invention provides an improved assay that demonstrates very large differences between AD cells and normal cells because it is based on the cytogenic response of an individual's cultured cells to fluorescent light in the presence and absence of a DNA repair inhibitor during the post-exposure period. This greater difference makes it possible to distinguish a single AD cell line (i.e., a cell line from one AD patient) from lines from most, if not all, normal people. The test is conducted on either skin fibroblasts or peripheral blood lymphocytes.
Inventors:
KK Sanford-Miffin, R Parshad, JH Robbins (NCI)
Patent Status:
Serial No. 08/611,330 filed 08 Mar 96 (CIP of 08/225,825, CIP of 07/957,315)
Portfolio:
Central Nervous System - Diagnostics, in vitro, other
For additional information, please contact:
Leopold J. Luberecki, Jr., J.D.
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7735 ext. 223
Fax: 301/402-0220