Abstract: A method of diagnosing a patient is carried out by delivering an aerosolized dose of a radioactive formulation to a patient and making a ventilation image of radioactive material deposited in the lung. This image is compared with a separately generated image (perfusion image) taken after injecting radiolabled particles into the pulmonary arterial circulation. A diagnosis of a pulmonary embolism can be made when areas of the lung which are shown in the ventilation image are not shown within the perfusion image, indicating that air flow to that area exists, whereas a blood flow to that area has been blocked. Devices, packaging and methodology for creating aerosols are provided which allow for efficient and repeatable delivery of radioaerosols to the lungs of a patient. Devices may be plug-in units or hand-held, self-contained units which are automatically actuated at the same release point in a patient's inspiratory flow cycle.

Abstract: DNA constructs are provided of epitope-tagged proteins or protein fragments which are conveniently purified with immunoaffinity chromatography such as epitope-tagged prion proteins (PrP). Transgenic animals expressing an epitope-tagged protein are provided, including transgenic animals expressing epitope-tagged PrP. Methods for distinguishing between the conformational shapes of a protein and a convenient method for isolating a tagged protein by immunoaffinity chromatographic methods are provided.

Abstract: Endothelial cells derived from subcutaneous adipose tissue are genetically modified to express the endothelial cell-specific angiogenic factor VEGF. The modified cells are sodded onto a vascular prosthesis for transplantation into an autologous or allogeneic recipient. The method accelerates endothelialization on the luminal surface of the vessel, and promotes collateral circulation in distal ischemic organs.

Abstract: Calcium phosphate cements are provided. The subject cements comprise amorphous calcium phosphate, at least one additional calcium source, usually an additional calcium phosphate, and a liquid component, such as a physiologically acceptable lubricant. Upon combination of the cement components, a flowable composition capable of setting in vivo into a solid calcium phosphate mineral product, such as hydroxyapatite, is produced. The subject cement compositions find use in a variety of applications, including the treatment of injured or compromised hard tissue.

Abstract: Sulfated disaccharides characterized by the ability to inhibit the binding of selectin to its physiologically-relevant ligand are disclosed. Included are efficient and inexpensive methods for producing the sulfated disaccharides, and methods for their therapeutic use and in in vivo and in vitro assays.

Abstract: Novel fluorescent dyes are provided, characterized by having a fluorophore joined to a cationic chain. The dyes are found to provide for high enhancement upon binding to nucleic acid and have strong binding affinities to the nucleic acid, as compared to the fluorophore without the polycationic chain. The dyes find use in detection of dsDNA in gel electrophoresis and solution at substantially higher sensitivities using substantially less dye.

Abstract: Flow cytometric methodology is provided for simultaneous determination of (1) ABO and Rh(D) typing of human red cells, (2) natural isoantibodies in plasma, and (3) screening for alloantibodies in plasma. The method includes (a) the use of a unique combination of fluorescent labelled antibodies to A, B and Rh(D) antigens to carry out (1); (b) different sized beads coated with blood group substances A & B to carry out (2); and (c) the differential fluorescent labelling of screening reagent red blood cells for flow cytometric analyses to carry out (3). The routine ABO and Rh(D) typing and antibody screening of human blood for both isoantibodies and alloantibodies can be determined in three individual reactions compared to 7 to 10 tests currently performed in blood banks.

Abstract: The gene responsible for the autosomal recessive mouse obesity mutation tub was identified by positional cloning. The homologous human gene is also provided. The genes are used to produce tubby protein; in screening for compositions that modulate the expression or function of the tubby protein; and in studying associated physiological pathways. The DNA is further used as a diagnostic for genetic predisposition to obesity, retinal degeneration or cochlear degeneration. The mutation responsible for the tub phenotype is a G to T transversion that abolishes a donor splice site in the 3' coding region and results in a larger transcript containing the unspliced intron. A second, prematurely truncated transcript arises from the introduction of a premature polyadenylation site in the unspliced intron.

Abstract: Neointimal cells are shown to express high levels of an anti-apoptotic gene, bcl-x, while the medial cells of the vessel itself express only low levels. The difference in gene expression exploited to provide for selective deletion of the neointimal cells. Apoptosis is induced by administering anti-sense bcl-x oligonucleotides to the affected vessel. Apoptosis is desirable as a treatment because it does not induce inflammation, further tissue injury or reactive hyperplasia. A significant reduction in lesion size is seen after treatment.

Abstract: Erectile dysfunction, particularly impotence, priapism and Peyronie's disease is treated by the transurethral administration of a therapeutically effective agent. The agents are administered to the urethra by means of a penile insert (1) having a rapidly releasing coating (4) containing the agent on its exterior surface or by means of an inserter (27) carrying an agent containing dose of agent (31) which can be displaced into the urethra.

Abstract: A bicycle frame which includes a shock absorber assembly which is coaxial and integral with the top tube of the frame. The entire shock absorber assembly is positioned within the top tube and thus completely forward of the seat tube and rearward of the head tube. The frame typically comprises two rear wheel support tubes each of which is integral with a rear wheel dropout at their lower end and each of which is detachably connected to one of two compression struts at its upper end. Each of the compression struts is separately, detachably and pivotally connected to the shock absorber assembly. The rear wheel dropout holds the axle of a rear wheel. The frame is configured such that when the rear wheel moves upward as in traversing a bump on the road the rear wheel dropout undergoes an arcuate motion which is translated to a linear motion of a piston in the shock absorber assembly via the rear wheel support tube and compression struts.

Abstract: A method for diagnosing vasculogenic erectile dysfunction, including vasculogenic impotence and Peyronie's syndrome, is provided. The method involves transurethral administration of a vasodilating agent to induce an erection, followed by hemodynamic evaluation using duplex ultrasonography, NMR, angiography, or the like. Kits for conducting the diagnostic method are provided as well, as are methods of treatment based on the diagnostic conclusion.

Abstract: The present invention provides a composition comprising a BPI Protein and an anionic compound which composition exhibits (1) no bactericidal activity and (2) endotoxin neutralizing activity. Also, this invention provides methods for using BPI Proteins.

Abstract: A device and method for the detection of small particles in a fluid. The device is a collapsible sample container having a opening which is covered, at least in part, by a porous membrane having a plurality (e.g., 100) of pores therein having a pore diameter equal to or smaller than the diameter of the particles to be detected (e.g., 01. to 100 microns). A means for collapsing the container to extrude the liquid sample through the membrane pores is provided along with a means for detecting pressure during the extrusion. The size and number of particles in the liquid is calculated by relating the extrusion pressure required to a pre-calibrated standard. When a constant pressure is applied the rate at which fluid is extruded decreases as the pores of the membrane become clogged with particles.

Abstract: The gene responsible for the autosomal recessive mouse obesity mutation tub was identified by positional cloning. The homologous human gene is also provided. The genes are used to produce tubby protein; in screening for compositions that modulate the expression or function of the tubby protein; and in studying associated physiological pathways. The DNA is further used as a diagnostic for genetic predisposition to obesity, retinal degeneration or cochlear degeneration. The mutation responsible for the tub phenotype is a G to T transversion that abolishes a donor splice site in the 3' coding region and results in a larger transcript containing the unspliced intron. A second, prematurely truncated transcript arises from the introduction of a premature polyadenylation site in the unspliced intron.

Abstract: A method of suppressing ventricular muscle cell hypertrophy induced by an .alpha..sub.1 -adrenergic agonist or endothelin, by providing an effective amount of a retinoic acid compound. Also provided are methods for identifying compounds which suppress ventricular muscle cell hypertrophy, compounds which inhibit the retinoic acid suppression of ventricular muscle cell hypertrophy, and therapeutic methods.

Abstract: Heteromultimeric fluorophores are provided for binding to DNA, which allow for the detection of DNA in electrical separations and preparation of probes having high-fluorescent efficiencies and large Stokes shifts. In addition, by appropriate choice of fluorescent molecules, one can use a single narrow wavelength band excitation light source, while obtaining fluorescent emissions having sufficient separation to be readily discriminated.

Abstract: The invention includes an artificial PrP gene, a transgenic animal containing a PrP gene of another animal or the artificial PrP gene, a hybrid non-human mammal with an ablated endogenous prion gene and exogenous prion gene and assay methodology which uses the animals to detect pathogenic prions in a sample or diagnose a cause of death. The artificial gene includes a sequence such that when it is inserted into the genome of a host animal (such as a mouse), the animal is rendered susceptible to infection with prions which normally would infect only a genetically diverse test animal (such as human, cow or sheep). The artificial PrP gene may be comprised of a completely artificial polynucleotide sequence. Alternatively, the artificial gene may be comprised of the codon sequence of a host animal with one or more codon substitutions being made wherein the substitutions are preferably corresponding PrP gene codons from a genetically diverse test animal.

Abstract: Novel fluorescent labeling techniques and fluorescent labels are provided, employing high affinity non-covalently binding and intercalating fluorescent dyes and dsDNA. The dyes find application to provide highly sensitive labeling of nucleic acids in electrophoretic gels and as pre-prepared labels for binding to a wide variety of specific binding pair members. The DNA-dye fluorescer complex can be used for labels in diagnostic assays, detection of specific nucleic acid sequences, and the like.

Abstract: Novel compounds useful as inhibitors of estrone sulfatase are provided. The compounds have the structural formula (I) ##STR1## wherein X and Y, or Y and Z, form an oxathiazine dioxide ring or a dihydro-oxathiazine dioxide ring, and the other various substituents are as defined herein. Pharmaceutical compositions and methods for using the compounds of formula (I) to treat estrogen-dependent disorders are provided as well.