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: The invention features a purified hyaluronidase BH55 polypeptide isolated from a mammalian species, preferably bovine or human. The invention also features DNA encoding BH55, vectors and transformed host cells containing DNA encoding BH55, the methods of making BH55 hyaluronidase polypeptides, and the antibodies that specifically bind BH55.

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 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. 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 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: 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.

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: 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 to obtain selected individual peptides or families thereof which have a target property and optionally to determine the amino acid sequence of a selected peptide or peptides to permit synthesis in practical quantities is disclosed. In general outline, the method of the invention comprises synthesizing a mixture of randomly or deliberately generated peptides using standard synthesis techniques, but adjusting the individual concentrations of the components of a mixture of sequentially added amino acids according to the coupling constants for each amino acid/amino acid coupling. The subgroup of peptides having the target property can then be selected, and either each peptide isolated and sequenced, or analysis performed on the mixture to permit its composition to be reproduced. Also included in the invention is an efficient method to determine the relevant coupling constants.

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: Liquid, flowable formulations including aqueous formulations of a pharmaceutically active drug are packaged in individual dosage unit containers which containers are interconnected to form a cellular array designed to be integrated into a dispensing device capable of individually opening dosage unit containers and aerosolizing the contents through a nozzle for delivery to a patient. The cellular array is comprised of a plurality of containers with each container having an opening(s) thereon from which a drug-containing formulation may be aerosolized. The dispensing device is a hand-held, self-contained, portable device comprised of a means for removing covers from the containers and automatically dispensing the formulation from individual containers, preferably in response to a signal obtained as a result of measuring the inspiratory flow of a patient.

Abstract: A transgenic, non-human animal model is disclosed which lacks receptors which mediate some of the central nervous system (CNS) actions of serotonin. The animal is preferably from a genus selected from the group consisting of Mus (e.g., mice), Rattus (e.g., rats), Oryctologus (e.g., rabbits) and Mesocricetus (e.g., hamsters). More preferably the animal is a mouse which lacks 5HT.sub.2c receptors. Animals lacking such receptors are overweight due to abnormal control of feeding behavior and are prone to spontaneous death from seizures. Thus, such animals provide an animal model for the testing of drugs which are potentially useful in the treatment of eating disorders and diseases such as epilepsy which result in seizures.

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: Compositions are administered to a patient (preferably by injection and locally) to treat a variety of conditions including inflammation associated with trauma and with certain aspects of diseases such as rheumatoid arthritis, psoriasis, insulin-dependent diabetes, cutaneous lymphomas, duodenal ulcer, chronic proctitis, lymphocytic thyroidiris, hemorphagic shock, reperfusion injury during transplantation and multiple sclerosis. The compositions are pharmaceutically acceptable injectable formulations which include an active component in a pharmaceutically acceptable carrier. The active component is a chlorate or selenate which inhibits the natural biochemical sulfation process and/or a sulfatase enzyme which removes a sulfate from a specific position of a saccharide molecule which makes up a part of a natural ligand for L-selectin. Removal of the sulfate from the ligand hinders the ability of the ligand to bind to its natural receptor (i.e.

Abstract: A method of controlling access to a drug in an aerosol drug delivery device by an electronic lock and key means is disclosed. Access is limited to the intended user by providing the intended user with a uniquely coded, machine readable key means that matches the unique code of the lock means. Contacting matching lock and key means signals a controlling means to allow use of the device. Specifically, the method is applied to a method of pain control provided by the intrapulmonary delivery of a pharmaceutically active pain relief formulation. The formulation is automatically released from a hand-held, self-contained, portable device comprised of a means for automatically releasing a measured amount of drug into the inspiratory flow path of a patient in response to information obtained from a means for measuring and separately determining inspiratory flow rate and inspiratory volume of a patient.

Abstract: A microcannula suitable for cannulation of very small blood vessels in a small animal, neonate or adult having a sharp pointed trochar tightly but removable placed in the lumen of the microcannula. The trochar is held in place by contact friction from an area of reduced inside diameter distal to the tip end, formed by welding the end distal of the microcannula to a tube having a slightly larger diameter. A process for making a microcannula.