Abstract: The need for the delivery of insulin by injection can be reduced or eliminated by a method whereby an aerosolized insulin formulation is delivered to a patient's lungs and the rate at which the insulin is absorbed into the blood is increased by the use of an inhale-exhale breathing maneuver. Particles of insulin delivered to the surface of lung tissue will be absorbed into the circulatory system. The rate of absorption is enhanced by instructing the patient to inhale maximally and thereafter exhale maximally. The insulin is delivered to the patient from a hand-held, self-contained device which automatically releases an aerosolized burst of formulation. The device includes a sensor which is preferably electronic which measures inspiratory flow and volume which measurement can be used to control the point of drug release. The sensor can also assist the patient in the inhale-exhale maneuver.

Abstract: A portable air temperature controlling device useful for warming air surrounding an aerosolized drug formulation is described. Warming the air of an aerosol makes it possible to reduce the size of aerosol particles produced by an aerosol generation device. Additionally, warming the air forces the size of the aerosol particles to be in the range required for systemic drug delivery independent of ambient conditions. Smaller particles can be more precisely targeted to different areas of the respiratory tract.

Abstract: A method for inspecting small holes in a material is disclosed. The method comprises directing a light source through the holes in the material, and then focusing the light passing through the material onto a CCD detector. The focusing techniques allow for a reduction in the size of the image which must be inspected, thereby increasing sample throughput, while still allowing for detailed inspection of the hole number and quality. Methods of producing an aerosolization container and device comprising membranes which pass such an inspection are also provided.

Abstract: The present invention provides assays for identifying the levels of both protease sensitive and protease resistant conformers of PrPSc in a sample. In a preferred embodiment, the assay comprises determining levels of total PrPSc in a sample, subjecting the PrPSc fraction to treatment with a protease that selectively hydrolyzes the protease sensitive PrPSc (sPrPSc) conformers, and quantifying the levels of sPrPSc in the sample. The ability to detect sPrPSc allows early detection of prions, since the PrPSc in easily accessible biological samples such as blood is predominantly sPrPSc. The ratio of sPrPSc to rPrPSc also allows the identification of a particular prion strain in an infected sample.

Abstract: Assay methodology of the invention allows for: (1) determining if a sample contains a conformation of a protein which is associated with disease and the concentration and amount of such if present; (2) determining the amount of protease resistant disease related protein in a sample and by subtracting that amount from the total amount of disease related protein present determining the amount of protease sensitive disease protein in the sample; and (3) determining the strain and incubation time of a disease related protein by (i) relating the relative amounts of protease resistant and protease sensitive protein to known strains to thereby determine the strain; and (ii) plotting the concentration of protease sensitive protein on a graph of incubation time versus concentration of protease sensitive protein for known strains to predict the incubation time of an unknown strain of pathogenic protein in a sample.

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: The present invention provides assays to identify compounds that affect microglial cell activation, and specifically assays to identify compounds that affect secretion of cytokines from these microglial cells by modulating PGE2-mediated activity. The assays of the invention include assays for testing microglial cell activation by contacting microglia with compounds that modulate &bgr;-amyloid PGE2-mediated activation, which can be identified by cellular activity such as secretion of cytokines, e.g., TNF-&agr; and IL-1&agr;. The effect of the candidate compound can be determined by comparing the effect with a control culture which is not contacted with the compound, or by comparing the effect with a standardized profile.

Abstract: The invention is directed to production of particles for introduction into food using a stable microjet and a monodisperse aerosol formed when the microjet dissociates. A variety of devices and methods are disclosed which allow for the formation of a stream of a first fluid (e.g. a liquid) characterized by forming a stable capillary microjet over a portion of the stream wherein the microjet portion of the stream is formed by a second fluid (e.g. a gas).

Abstract: The present invention provides cell-free &ggr;-secretase activity. The method of the invention utilizes a membrane source of APP/&ggr;-secretase mixture in the assay to determine factors that may enhance or decrease enzymatic activity affecting &bgr;-amyloid peptide production. The cell membranes used in the assay may be from cells expressing an endogenous APP or, preferably, cells expressing a recombinant APP. The APP may be full-length or a fragment capable of being proteolytically cleaved by &ggr;-secretase. In addition, the APP expressed in the cells may have one or more mutation, such as a point mutation, small deletion, etc.

Abstract: A controlled release formulation of lipoic acid is disclosed. The lipoic acid is combined with excipient materials in such a way that those materials provide for gradual release of the lipoic acid in a manner which makes it possible to substantially increase the period of time over which therapeutic levels of lipoic acid are maintained relative to a quick release formulation. These features make it possible to use lipoic acid to reduce serum glucose levels and maintain those levels over time thereby obtaining a range of desired therapeutic results.

Abstract: Antibodies are disclosed which specifically bind to native PrPSc in situ. Preferred antibodies bind only to the native PrPSc of a particular species e.g., human, cow, sheep, pig, etc. Particularly preferred antibodies bind specifically to a particular isoform of human PrPSc. Preferred antibodies of the invention are (1) produced by phage display methodology, (2) bind specifically to native PrPSc, (3) neutralizes the infectivity of prions, (4) bind to PrPSc in situ and (5) bind 50% or more of PrPSc in a liquid flowable sample. Antibodies of the invention can be bound to a substrate and used to assay a sample (which has any PrPc denatured via proteinase K) for the presence of PrPSc of a specific species which PrPSc is associated with disease. Antibodies which specifically bind to human PrPSc can be labeled and injected carrying out an in vivo diagnostic test to determine if the human is infected with prions associated with disease.

Abstract: A human monoclonal antibody useful for the treatment of various diseases caused by human connective tissue growth factor (CTGF) and preventing the onset of the above diseases; medicinal uses thereof; and various monoclonal antibodies having various characteristics against various mammalian CTGFs useful for detecting and assaying CTGFs present in body fluids of mammals suffering from various diseases.

Abstract: Electroporation is performed in a controlled manner in either individual or multiple biological cells or biological tissue by monitoring the electrical impedance, defined herein as the ratio of current to voltage in the electroporation cell. The impedance detects the onset of electroporation in the biological cell(s), and this information is used to control the intensity and duration of the voltage to assure that electroporation has occurred without destroying the cell(s). This is applicable to electroporation in general. In addition, a particular method and apparatus are disclosed in which electroporation and/or mass transfer across a cell membrane are accomplished by securing a cell across an opening in a barrier between two chambers such that the cell closes the opening. The barrier is either electrically insulating, impermeable to the solute, or both, depending on whether pore formation, diffusive transport of the solute across the membrane, or both are sought.

Abstract: The present invention provides aeration methods using spherical gas bubbles having a size on the order of 0.1 to 100 microns in size. A device of the invention for producing a monodispersion of bubbles includes a source of a stream of gas which is forced through a liquid held under pressure in a pressure chamber with an exit opening therein. The stream of gas surrounded by the liquid in the pressure chamber flows out of an exit orifice of the chamber into a liquid thereby creating a monodispersion of bubbles with substantially uniform diameter. The bubbles are small in size and produced with a relatively small amount of energy relative to comparable systems. Applications of the aeration technology range from oxygenating sewage with monodispersions of bubbles to oxygenation of water for fish maintenance.

Abstract: The invention is directed to a stable capillary microjet and a monodisperse aerosol formed when the microjet dissociates. A variety of devices and methods are disclosed which allow for the formation of a stream of a first fluid (e.g. a liquid) characterized by forming a stable capillary microjet over a portion of the stream wherein the microjet portion of the stream is formed by a second fluid (e.g. a gas). The second fluid is preferably in a different state from the first fluid—liquid-gas or gas-liquid combinations. However, the first and second fluids may be two different fluids in miscible in each other.

Abstract: A nozzle comprised of a thin, flexible membrane material having a plurality of pores is disclosed. In one embodiment, the pores have an unflexed exit aperture diameter in the range of about 0.5 to about 2 microns (preferably about 1 micron) and are positioned substantially uniformly in the material, preferably about 50 microns apart. The nozzle preferably has a conical or trumpet-shaped cross-section. In another aspect of the invention, the exit aperture of the nozzle is surrounded by an elevated area protruding above the substantially planar exit side of the membrane in order to prevent intrusion of liquid back into the nozzle. The nozzle can be used to form an aerosol containing a pharmaceutical composition from the exit side of the nozzle upon forcible application of the composition to the entrance side of the nozzle. This aerosol can be used to administer the pharmaceutical composition, for example, to the eye or to a selected portion of the respiratory tract.

Abstract: The present invention provides antibodies that specifically bind with a high degree of binding affinity to a native ungulate PrPC and/or a denatured ungulate PrPSc, but not to a native ungulate PrPSc. Preferred antibodies find native bovine PrPC and treated PrPSc but not native bovine PrPSc and can be used in an assay to determine if a sample is infected with infectious prions, i.e. PrPSc.

Abstract: A method of sterilizing objects as well as the sterilized objects obtained from the method are disclosed. The method involves contacting an object such as a medical device to be reused with polycationic dendrimer under conditions which result in rendering a conformationally altered protein (e.g. a prion) non-infectious. A disinfecting agent or surgical scrub composition which comprises the dendrimers is also disclosed as are gelatin capsules treated with polycationic dendrimers.

Abstract: An electrical current is created across an electrically conductive medium comprising a cell which may be part of a tissue of a living organism. A first electrical parameter which may be current, voltage, or electrical impedance is measured. A second electrical parameter which may be current, voltage or a combination of both is then adjusted and/or analyzed. Adjustments are carried out to facilitate analysis and/or obtain a desired degree of electroporation. Analysis is carried out to determine characteristics of the cell membrane and/or tissue.

Abstract: Spherical particles having a size on the order of 0.1 to 100 microns in size are created by systems and devices of several types. The device includes a source of a stream of gas which is forced through a liquid held under pressure in a pressure chamber with an exit opening therein. The stream of gas surrounded by the liquid in the pressure chamber flows out of an exit orifice of the chamber into a liquid thereby creating a monodispersion of bubbles with substantially uniform diameter. The bubbles are small in size and produced with a relatively small amount of energy relative to comparable systems. Small particles of liquid may also be produced. Applications of the technology range from oxygenating sewage with monodispersions of bubbles to inhalation therapy with monodisperse aerosol dispersions of pharmaceutically active drugs.