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: 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: 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: 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: A portable, battery powered, hand-held system for releasing a controlled dose of aerosol medication for inhalation by a patient including a durable body and a medication cassette inserted in the durable body. The cassette includes a housing for containing a canister of medication, bears an identification code, and permits the canister to be manually depressed to release a dose, e.g., a metered dose, when out of the durable body. The durable body includes an actuator mechanism for engaging an inserted cassette and its canister, and an actuator release mechanism for controlling the actuator mechanism to depress the canister for a selected period of time to release the desired dose of medication and then the release the canister. The actuator mechanism, includes a compression spring for depressing the canister and a torsion spring for reloading the compression spring. The torsion spring is reloaded by rotating the cassette from an open position for delivering aerosol to a closed position.

Abstract: Prion protein (PrP) peptides having at least one .alpha.-helical domain and forming a random coil conformation in aqueous solutions bind cellular PrP (PrP.sup.C) to form a complex having characteristics of the scrapie isoform (PrP.sup.Sc). Methods for screening compounds able to inhibit or decrease the binding of PrP peptides to PrP.sup.C are disclosed, as well as methods for assaying PrP.sup.Sc.

Abstract: A new protein is described, prostaglandin F.sub.2.alpha. receptor regulatory protein (FPRP), which is able to inhibit the binding of prostaglandin F.sub.2.alpha. (PGF.sub.2.alpha.) to its receptor (FP). Included are pharmaceutical compositions of FPRP and FPRP variants for treatment of PGF.sub.2.alpha. -mediated disorders, and assays for detecting FP in a biological sample.

Abstract: Several natural polypeptides (basophil granule proteins, "BGP") derived from the cytoplasmic granules of human basophils, and modified forms thereof, are described. These polypeptides, the DNA which encodes them and antibodies which recognize them, are useful as diagnostics for, and treatments for, pathologies involving inflammatory and IgE-mediated responses, parasitic and helminthic infections, hypersensitivity reactions and certain types of leukocytic leukemias.

Abstract: An artificial plasma-like substance having at least one water soluble polysaccharide oncotic agent selected from the group consisting of high molecular weight hydroxyethyl starch, low molecular weight hydroxyethyl starch, dextran 40 and dextran 70, and albumin which is buffered by lactate and has a pre-administration pH of between 5 and 6.5 is disclosed. Also disclosed is an artificial plasma-like solution having at least two water soluble polysaccharide oncotic agents one of which is eliminated from the circulation slowly and the other of which is eliminated from the circulation quickly. Supplimentation of the plasma-like solution with certain ions is described. A system for administration of the plasma-like solution to a subject wherein the system comprises a first and second solution each having particular buffers is described. The plasma-like solution including cryoprotective adducts is also disclosed.

Abstract: A method for releasing a controlled amount of aerosol medication is disclosed. The method of the invention is preferably used in connection with a portable, battery-powered, hand-held system for releasing a controlled dose of aerosol medication for inhalation by a patient. The inhalation breath flow of the user of the apparatus is monitored and the inhalation flow rate is measured, and inhalation volume is determined as a function of the measured flow rate. The measured flow rate is compared to predetermined minimum and maximum flow rate thresholds, and the determined flow volume is compared to predetermined minimum and maximum flow volume thresholds. When both the measured flow rate and the measured flow volume are between their respective the minimum and maximum thresholds, a signal is provided to release a controlled amount of aerosol.

Abstract: The invention features methods for measuring the total amounts of G protein-bound GDP and GTP in mammalian cells and tissue. The method of the invention is advantageous over conventional methods in that the cells need not be exposed to phosphate-free growth conditions, which can adversely affect the accuracy of the GTP determination. Moreover, the method does not require exposure of the cells to radiolabelled phosphate in the growth medium. Standardized amounts of G protein-bound GDP and GTP are determined relative to non-nuclear cellular protein content or cellular DNA content, allowing comparison of results across different cell types. The method is particularly applicable to the detection of Ras protein bound GTP and GDP.

Abstract: A chemical signal-impermeable mask is positioned in the electrolyte flow such that the mask is between a source of chemical signal and a working electrode which senses the chemical signal transported from the source (e.g., by diffusion). The configuration of the mask is such that the mask prevents substantially all chemical signal transport from the chemical signal source having a radial vector component relative to a plane of the mask and the catalytic face of the working electrode, thus allowing primarily only chemical signal transport that is substantially perpendicular to the place of the mask and the catalytic surface of the working electrode. By reducing or eliminating chemical signal radial transport toward the working electrode, the mask thus significantly reduces or eliminates edge effects. By substantially reducing edge effects created by radial transport of chemical signal, it is possible to obtain a more accurate measurement of the amount (e.g.