Abstract: Dosages of inhaled insulin are controlled within a narrow range by controlling the total volume of air inhaled by a patient. By repeatedly delivering aerosolized insulin with the same total inhaled volume of air, the amount of insulin delivered to the patient each time is consistent. A device for delivering insulin by inhalation is disclosed which device comprises a means for measuring inhaled volume and for halting inhalation at a pre-determined point. The device also comprises an adjustable means for applying various amounts of force to a container of formulation to expel different amounts of drug from the container based on the force applied.

Abstract: Devices, packaging and methodology for efficiently and repeatably creating aerosolized bursts of a formulation of respiratory drug are disclosed. Devices are hand-held, self-contained units which are automatically actuated at the same release point in a patient's inspiratory flow cycle. The release point is automatically determined either mechanically or, more preferably calculated by a microprocessor which receives data from a sensor making it possible to determine inspiratory flow rate and inspiratory volume. The device is loaded with a cassette comprised of an outer housing which holds a package of individual collapsible containers of formulation which comprises a respiratory drug useful in topically treating lung tissue. Actuation of the device forces respiratory drug through a porous membrane of the container which membrane has pores having a diameter in the range of about 0.25 to 6.0 microns. The porous membrane is positioned in alignment with a surface of a channel through which a patient inhales air.

Abstract: Devices, packaging and methodology for efficiently and repeatably creating aerosolized bursts of an insulin containing formulation are disclosed. Devices are hand-held, self-contained units which are automatically actuated at the same release point in a patient's inspiratory flow cycle. The release point is automatically determined either mechanically or, more preferably calculated by a microprocessor which receives data from a sensor making it possible to determine inspiratory flow rate and inspiratory volume. The device is loaded with a cassette comprised of an outer housing which holds a package of individual disposable collapsible containers of an insulin containing formulation for systemic delivery. Actuation of the device forces insulin formulation through a porous membrane of the container which membrane has pores having a diameter in the range of about 0.25 to 3.0 microns, preferably 0.25 to 1.5 microns.

Abstract: An aerosol formulation of an aerosol propellant and a base form of a narcotic drug selected from the group consisting of fentanyl, sufentanil and remfentanyl is provided. Such a formulation allows for the drug to be dissolved within the propellant and used within a device which does not require the use of a lubricant. Formulations are also disclosed which include lubricants, wherein the lubricant and propellant are both either polar or both non-polar. Thus, the lubricant component does not act as a solvent or cosolvent, but rather acts as a lubricant for the valve used for dispersing the formulation to a patient. Typical non-polar propellants include chlorofluorocarbons, which are typically used in connection with non-polar lubricants such as saturated vegetable oils, e.g. fractionated coconut oils. Typical polar propellants include hydrofluoroalkanes, which are typically used in connection with polar lubricants such as polyethylene glycols.

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 protein gene and exogenous prion protein gene, assay methodology which uses the animals to detect pathogenic prions in a sample or diagnose a cause of death and standardized prion preparation used in the assay. The genome of a host animal (such as a mouse), is manipulated so that 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). Pathogenic prions in a sample can be detected by injecting the sample to be tested into a mammal of the invention which has been genetically manipulated so as to be susceptible to infection from prions in the sample.

Abstract: Methodology and devices for delivering aerosolized formulation to target areas of a patient's respiratory tract are disclosed. The device is a hand-held, self-contained unit which is readily portable and capable of measuring a variety of parameters including the patient's total respiratory tract capacity, inspiratory flow rate and inspiratory volume. The device is loaded with a container which includes a drug formulation in a liquid form which container includes an opening which is covered, at least in part, by a porous membrane. The pore sizes are designed so as to provide aerosolized particle sizes which are tailored in size for delivery to the specific target area of the respiratory tract. The device can allow the patient to inhale a predetermined volume of unaerosolized air followed by a predetermined volume of aerosol after which flow can be shut off completely or followed by additional aerosol free air.

Abstract: A chamber suitable for placing a subject under a pressure greater than atmospheric pressure with means for perfusing, cooling and respiring the subject. The chamber can be used in conjuction with low temperature surgical procedures.

Abstract: An assay method is disclosed which makes it possible to determine the presence of a diseased related conformation of a protein (e.g., PrP.sup.Sc) in a sample. A sample is divided into two portions and the first portion is cross-linked to a first solid support and then contacted with a labelled antibody which binds to a non-disease form of the protein with a higher degree of affinity (e.g, 4 to 30 fold higher) than to the disease form of the protein. The second portion is treated in a manner which causes any disease form of the protein to change conformation to a form with a higher binding affinity for the labelled antibody. The treated second portion is then bound to a second solid support and contacted with labelled antibody. The level of labelled antibody binding to a protein in the first and second portions is determined and the amounts measured in each are compared.

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 monomeric insulin and/or an inhale-exhale breathing maneuver. Particles of insulin and in particular monomeric insulin delivered to the surface of lung tissue will be absorbed into the circulatory system. The rate of absorption is enhanced by the monomeric form of insulin and by instructing the patient to inhale maximally and thereafter exhale maximally. This maneuver causes a spike in the rate at which insulin enters the circulatory system thereby increasing the rate at which glucose is removed from the circulatory system. The insulin or insulin analog may be a dry powder but is preferably in a liquid formulation delivered to the patient from a hand-held, self-contained device which automatically releases an aerosolized burst of formulation.

Abstract: A method for reconstructing corroded pipes is disclosed in which a long, new pipe can be inserted smoothly and without excessive force, into an older pipe. The method involves the insertion of a new pipe into an old pipe using a dolly to transfer the reaction force. The tail end of the new pipe is attached to the dolly, and the front end of the new pipe is sealed off. A plug is inserted into the dolly from the tail end of the new pipe, which is filled with pressurized water. The dolly is then moved in the direction of the old pipe to insert the new pipe into the old pipe.

Abstract: Dosages of inhaled insulin are controlled within a narrow range by controlling the total volume of air inhaled by a patient. By repeatedly delivering aerosolized insulin with the same total inhaled volume of air, the amount of insulin delivered to the patient each time is consistent. A device for delivering insulin by inhalation is disclosed which device comprises a means for measuring inhaled volume and for halting inhalation at a pre-determined point. The device also comprises an adjustable means for applying various amounts of force to a container of formulation to expel different amounts of drug from the container based on the force applied.

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 monomeric insulin and/or an inhale-exhale breathing maneuver. Particles of insulin and in particular monomeric insulin delivered to the surface of lung tissue will be absorbed into the circulatory system. The rate of absorption is enhanced by the monomeric form of insulin and by instructing the patient to inhale maximally and thereafter exhale maximally. This maneuver causes a spike in the rate at which insulin enters the circulatory system thereby increasing the rate at which glucose is removed from the circulatory system. The insulin or insulin analog may be a dry powder but is preferably in a liquid formulation delivered to the patient from a hand-held, self-contained device which automatically releases an aerosolized burst of formulation.

Abstract: Isolated human herpesvirus type 8 nucleic acid sequences expressed in latently infected human cells including primary Kaposi's sarcoma cells, primary pulmonary tumor cells, and a body cavity based lymphoma cell line are disclosed. Methods of detecting HHV-8 infection and methods of inhibiting expression of the nucleic acid sequences in vivo are also disclosed.

Abstract: A newly discovered family of AIDS-associated viruses, designated ARV, is described. The viruses were isolated from AIDS patients from San Francisco and (a) are type D retroviruses; (b) have Mg.sup.++ --dependent reverse transcriptase activity; (c) induce human multinucleated cells without immortalizing the cells; (d) are replicable in HUT-78 human T cells; and (e) induce viral protein(s) in HUT-78 that binds to Ig from AIDS patients. The infected HUT-78 cells and immunogenic polypeptides derived from the viruses are useful for diagnosing AIDS.

Abstract: Devices for the generation of inhalable aerosols by extrusion through a porous membrane by a motor-driven cam assembly are disclosed. The device holds a drug formulation container in a drug release position. The package is comprised of a collapsible wall with an opening and a cover for the opening that includes a porous membrane having a plurality of pores therein with a diameter in the range of 0.5 to 6.0 microns. An electric motor in the device is powered by a battery to rotate a cam assembly having three cams. The first cam forces a clamping member (configured to correspond to the outer periphery of the container) against the periphery of the collapsible wall of the container, sealing the jointure of the collapsible wall to the cover of the container along the entire periphery, except for a small unsealed portion thereof. The second cam crushes the collapsible wall, forcing the contents of the container through the unsealed portion of the jointure.

Abstract: Stem cells transduced with HOXB4 exhibit enhanced in vitro and in vivo ability for self-regeneration and generate higher-numbers of tranplantable pluripotent hematopoietic stem cells relative to control and nonmanipulated cells.

Abstract: Apparatus and methods for delivering an amount of aerosolized medicine for inspiration by a patient in response to the occurrence of appropriate delivery point or points in the patient's detected breath flow. The aerosol medication may be administered as one or more pulses having a pulse width, shape, and frequency that will maximize the respirable fraction of the aerosolized compound being administered. The delivery point or points may be predetermined or determined from a prior inspiratory flow for depositing the selected medication at one or more desired locations in the patient's airway. Determined delivery points are recursively lowered for each inspiratory flow that does not satisfy one of the predetermined and previously lowered threshold.

Abstract: An enveloped vector particle contains gag and pol proteins from a retrovirus, a nucleic acid sequence and an envelope that includes VSV G envelope glycoprotein. The vector particle can be used to introduce nucleic acids into cells.

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: Recombinant methods and materials useful in producing lactoperoxidases are disclosed. An illustrative form of lactoperoxidase is the bovine protein shown in FIG. 1. FIG. 1 also shows the DNA sequence natively encoding the bovine lactoperoxidase, including contiguous regions of the gene. Such DNAs are useful in a variety of applications including antisense technology, formation of triple helices, and performance of diagnostic assays.