Abstract: Novel O.sup.6 -substituted guanine compounds and pharmaceutical compositions thereof are useful for effectively reducing O.sup.6 -alkylguanine-DNA alkyltransferase (AGT). The novel compounds are useful for treating tumors and when used with anti-neoplastic alkylating agents enhance the chemotherapeutic treatment of tumor cells in a host.
Type:
Grant
Filed:
June 7, 1994
Date of Patent:
November 25, 1997
Assignees:
The United States of America as represented by the Department of Health and Human Services, The Penn State Research Foundation, Arch Development Corporation
Inventors:
Robert C. Moschel, M. Eileen Dolan, Anthony E. Pegg, Mark G. McDougall, Mi-Young Chae
Abstract: Thermodynamically-unstable complexing agents which are diphosphonic acids and diphosphonic acid derivatives (or sulphur containing analogs), like carboxyhydroxymethanediphosphonic acid and vinylidene-1,1-diphosphonic acid, are capable of complexing with metal ions, and especially metal ions in the II, III, IV, V and VI oxidation states, to form stable, water-soluble metal ion complexes in moderately alkaline to highly-acidic media. However, the complexing agents can be decomposed, under mild conditions, into non-organic compounds which, for many purposes are environmentally-nondamaging compounds thereby degrading the complex and releasing the metal ion for disposal or recovery. Uses for such complexing agents as well as methods for their manufacture are also described.
Type:
Grant
Filed:
July 7, 1994
Date of Patent:
October 14, 1997
Assignee:
Arch Development Corporation
Inventors:
Earl Philip Horwitz, Ralph Carl Gatrone, Kenneth LaVerne Nash
Abstract: A method for automated detection of abnormal anatomic regions, wherein a mammogram is digitized to produce a digital image and the digital image is processed using local edge gradient analysis and linear pattern analysis in addition to feature extraction routines to identify abnormal anatomic regions. Noise reduction filtering and pit-filling/spike-removal filtering techniques are also provided. Multiple difference imaging techniques are also used in which difference images employing different filter characteristics are obtained and processing results logically OR'ed to identify abnormal anatomic regions. In another embodiment the processing results with and without noise reduction filtering are logically AND'ed to improve detection sensitivity. Also, in another embodiment the wavelet transform is utilized in the identification and detection of abnormal regions.
Type:
Grant
Filed:
August 8, 1996
Date of Patent:
September 30, 1997
Assignee:
Arch Development Corporation
Inventors:
Robert M. Nishikawa, Takehiro Ema, Hiroyuki Yoshida, Kunio Doi
Abstract: A method and system for the detection of anatomical features in a digital chest radiograph, and in particular rib edges and pneumothorax, wherein vertical profiles are defined in regions of the lungs in the radiograph, and a model function is fitted to the profiles to obtain initial estimates of the locations of rib edges. Gradient-histogram analysis is performed by determining edge gradient and their corresponding orientations in regions of interest (ROIs) defined in the radiograph in the vicinity of the initially estimated rib edges, determining the maximum edge gradient in each of the ROIs, and forming histograms which define accurate detections of rib edges. The edges are fitted with an elliptical function and a representation of the entire rib cage structure is obtained. The method and system are also applied to the detection of pneumothorax where ROIs are defined in the apical lung region and edge gradients and their orientations are detected in the ROIs.
Abstract: A method for automated detection of abnormal anatomic regions, wherein a mammogram is digitized to produce a digital image and the digital image is processed using local edge gradient analysis and linear pattern analysis in addition to feature extraction routines to identify abnormal anatomic regions. Noise reduction filtering and pit-filling/spike-removal filtering techniques are also provided. Multiple difference imaging techniques are also used in which difference images employing different filter characteristics are obtained and processing results logically OR'ed to identify abnormal anatomic regions. In another embodiment the processing results with and without noise reduction filtering are logically AND'ed to improve detection sensitivity. Also, in another embodiment the wavelet transform is utilized in the identification and detection of abnormal regions.
Type:
Grant
Filed:
September 29, 1995
Date of Patent:
September 9, 1997
Assignee:
Arch Development Corporation
Inventors:
Robert M. Nishikawa, Takehiro Ema, Hiroyuki Yoshida, Kunio Doi
Abstract: A semiconstrained prosthetic knee for surgical replacement of a dysfunctional knee includes a tibial platform, a movable bearing element, and a femoral component. The femoral component includes a polycentric convex bearing which slidably engages a movable bearing. The superior surface of the bearing element is designed to congruently slidably engage the inferior surface of the bearing portion of the femoral component throughout the flexion/extension range of the knee. The superior surface of the tibial platform is generally flat and includes at least one protrusion for controlling the movement of the bearing element. A stabilized prosthetic knee also includes a posterior stabilization member and may further include an anterior stabilization member upon the bearing element. The femoral component and the bearing element articulate in at least two radii of curvature and are also provided with an additional articulation surface and a complementary bearing surface.
Type:
Grant
Filed:
February 6, 1995
Date of Patent:
August 19, 1997
Assignee:
Arch Development
Inventors:
Louis F. Draganich, Lawrence A. Pottenger
Abstract: A method and system for the automated detection of lesions such as masses and/or tissue (parenchymal) distortions in medical images such as mammograms. Dense regions and subcutaneous fat regions within a mammogram are segmented. A background correction may be performed within the dense regions. Hough spectrum within ROIs placed in the breast region of a mammogram are calculated and thresholded using the intensity value .eta. in order to increase sensitivity and reduce the number of false-positive detections. Lesions are detected based on the thresholded Hough spectra. The thresholded Hough spectra are also used to differentiate between benign and malignant masses.
Type:
Grant
Filed:
February 24, 1995
Date of Patent:
August 12, 1997
Assignee:
Arch Development Corporation
Inventors:
Maryellen L. Giger, Ming Zhang, Ping Lu
Abstract: The present invention relates to synthetic herpes simplex virus (HSV) promoters which are constructed by operatively linking the 5' nontranscribed domain of an HSV .alpha. gene to a fragment containing the transcription initiation site and the 5' transcribed noncoding region from an HSV .gamma. gene. Synthetic promoters of the invention that are operatively linked to heterologous genes, inserted into HSV genomes and used to generate live virus are useful for expressing polypeptides encoded by the heterologous genes in appropriate host cells. The synthetic promoters direct transcription of the heterologous genes constitutively throughout the reproductive cycle of the virus at a high cumulative level. The recombinant viruses of the invention can also be used as vaccines to present polypeptides against which a host will mount an immune response.
Abstract: Treatment of cells with ionizing radiation is associated with the production of arachidonic acid. Inhibition of phospholipase A2 abolishes radiation-mediated arachidonate production, protein kinase C induction and tumor necrosis factor gene expression. The addition of inhibitors of lipoxygenase, such as ketoconazole, prior to irradiation reduces the expression of of tumor necrosis factor while maintaining the expression of other radiation inducible genes, such as Egr-1 and c-jun. In contrast, indomethacin, an inhibitor of cyclooxygenase, enhanced the expression of tumor necrosis factor as well as other radiation inducible genes. The results show that lipoxygenase inhibitors are useful in the treatment of radiation-induced mucositis, dermatitis, pneumonitis, proctitis, and esophagitis. which may be due to the production of cytokines such as TNF.
Type:
Grant
Filed:
July 20, 1994
Date of Patent:
June 24, 1997
Assignees:
Arch Development Corp., Dana-Farber Cancer Institute
Inventors:
Ralph R. Weichselbaum, Dennis E. Hallahan, Donald W. Kufe
Abstract: The invention relates generally to compositions of and methods for obtaining ubiquitous, nuclear receptor (UR) polypeptides. The invention also relates to polynucleotides encoding UR polypeptides, recombinant host cells and vectors containing UR-encoding polynucleotide sequences, and recombinant UR polypeptides. By way of example, the invention discloses the cloning and functional expression of at least two different UR polypeptides. The invention also includes methods for using the isolated, recombinant receptor polypeptides in assays designed to select substances which interact with UR polypeptides for use in diagnostic, drug design and therapeutic applications.
Abstract: A method for the automated detection of gross abnormalities and asymmetries in chest images, including generating image data from radiographic images of the thorax. The image data are then analyzed in order to produce the boundaries of the aerated lung regions in the thorax. This analysis comprises location of the mediastinum and lung apices, iterative global thresholding with centroid testing of contours, local thresholding on regions along initial contours of the aerated lung, correction for regions near the costo- and cardiophrenic angles in the chest, analysis of the areas and density distribution within the aerated lung regions in the chest and determination of the likelihood of the presence of a gross abnormality or asymmetry. Final output could be the computer determined contours of the lungs or the likelihood for abnormality.
Type:
Grant
Filed:
November 30, 1993
Date of Patent:
June 10, 1997
Assignee:
Arch Development Corporation
Inventors:
Maryellen L. Giger, Samuel Armato, Heber MacMahon
Abstract: A method and system for monitoring an industrial process and a sensor. The method and system include generating a first and second signal characteristic of an industrial process variable. One of the signals can be an artificial signal generated by an auto regressive moving average technique. After obtaining two signals associated with one physical variable, a difference function is obtained by determining the arithmetic difference between the two pairs of signals over time. A frequency domain transformation is made of the difference function to obtain Fourier modes describing a composite function. A residual function is obtained by subtracting the composite function from the difference function and the residual function (free of nonwhite noise) is analyzed by a statistical probability ratio test.
Type:
Grant
Filed:
April 8, 1996
Date of Patent:
May 13, 1997
Assignee:
ARCH Development Corporation
Inventors:
Kenneth C. Gross, Kristin K. Hoyer, Keith E. Humenik
Abstract: A method for simultaneously partitioning a metal oxide and silica from a material containing silica and the metal oxide, using a biphasic aqueous medium having immiscible salt and polymer phases.
Abstract: A method and system for computer-aided differential diagnosis of diseases, and in particular, computer-aided differential diagnosis using neural networks. A first embodiment of the neural network distinguishes between a plurality of interstitial lung diseases on the basis of inputted clinical parameters and radiographic information. A second embodiment distinguishes between malignant and benign mammographic cases based upon similar inputted clinical and radiographic information. The neural networks were first trained using a hypothetical data base made up of hypothetical cases for each of the interstitial lung diseases and for malignant and benign cases. The performance of the neural network was evaluated using receiver operating characteristics (ROC) analysis. The decision performance of the neural network was compared to experienced radiologists and achieved a high performance comparable to that of the experienced radiologists.
Abstract: An autocrine crystal adhesion inhibitor called CAI is an anionic, sialic acid-containing glycoprotein secreted by kidney epithelial cells that blocks adhesion of calcium oxalate monohydrate (COM) crystals to the cell surfaces. Persons may be classified according to risk of developing kidney stones, by measuring the amount of CAI in a biological sample. Treatment efficacy is also monitored by this method. CAI is administered in vivo to prevent nephrolithiasis. A rapid, simple assay to detect agents that inhibit adhesion of COM crystals to the surface of kidney epithelial cells is characterized.
Abstract: An ion exchange resin is disclosed that is comprised of an insoluble copolymer onto which are grafted pendent groups that provide 1.0 to about 10 mmol/g dry weight phosphorous. The pendent groups have the formula ##STR1## wherein R is hydrogen, a cation or mixtures thereof; andR.sup.1 is hydrogen or an C.sub.1 -C.sub.2 alkyl group. The resin also contains zero to about 5 mmol/g dry weight of pendent aromatic sulfonate groups. Processes for making and using an ion exchange resin are also disclosed.
Type:
Grant
Filed:
February 6, 1995
Date of Patent:
April 8, 1997
Assignees:
Arch Development Corp., The University of Tennessee Research Corp.
Inventors:
Andrzej W. Trochimcznk, Ralph C. Gatrone, Spiro Alexandratos, E. Philip Horwitz
Abstract: Disclosed are DNA sequences encoding DNA binding polypeptides including androgen receptor (AR) and TR2 polypeptides. Illustratively, human and rat AR-cDNA have 79 kD and 98 kD polypeptide expression products which are immunoprecipitable by human auto-immune anti-androgen receptor antibodies and are capable of binding androgens specifically and with high affinity. Also disclosed are antibodies and immunological methods and materials for detection of androgen receptor and TR2 polypeptides and hybridization methods and materials for detection of AR-and TR2-related nucleic acids.
Abstract: p-Sulfoxy cinnamic acid isolated from methanolic extracts of the eelgrass Zostera marina having significant antifouling aquatic properties. p-Sulfoxy cinnamic acid was synthesized in the laboratory from p-coumaric acid, and antifouling activity was identical to the natural compound in laboratory bioassays. In addition, sulfate esters of other phenolic acids showed similar antifouling activity, suggesting that the sulfate ester was responsible for the antifouling effect.
Type:
Grant
Filed:
December 8, 1994
Date of Patent:
March 4, 1997
Assignees:
ARCH Development Corporation, The Regents of the University of California
Inventors:
Richard C. Zimmerman, Randall S. Alberte, James S. Todd, Phillip Crews
Abstract: Novel methods for the treatment of tissue damage resulting from cell membrane permeabilization due to electrical injury are disclosed. Such methods include treatment with a surface active copolymer which is herein shown to promote membrane repair. The administration of Poloxamer 188 is shown to reduce tissue inflammation and damage following electrical injury in vivo. Also disclosed are methods for the treatment of cell and tissue damage after electrical injury using a surface active copolymer in combination with a high energy phosphate compound capable of recharging cellular energy stores and potentiating cell repair and survival. Compositions comprising surface active copolymers for intravenous, intramuscular, and topical use are also disclosed, along with novel compositions comprising a combination of a surface active copolymer and a high energy phosphate compound.
Abstract: Disclosed are a novel class of antiandrogenic compounds including saturated and unsaturated fatty acids, catechin gallates, their derivatives, and synthetic analogs, their method of synthesis, and their use in treating disorders associated with androgenic activities. Also disclosed is the use of known compounds not previously known for their antiandrogenic activity in treating disorders related to androgenic activities and cancers.