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: Switch regions derived from an immunoglobulin (Ig) gene are used to direct recombination between a targeting construct containing a promoter, a switch region (S.sub.1), and 2) a target locus minimally containing a promoter, a switch region (S.sub.2), and a target sequence.

Abstract: Aqueous solutions comprising a polysaccharide oncotic agent, a physiologically compatible buffer, a simple hexose sugar, dissolved chloride salts of calcium, sodium and magnesium, and a dissolved organic salt of sodium are disclosed. The solutions are effective substitutes for blood and may be used to preserve the biological integrity of the organs of a mammalian donor organism as shown by superior anatomical integrity of cryopreserved organs and tissues of subjects perfused with the solution. The solutions may be used for maintaining a partially or substantially completely exsanguinated subject at normal temperatures and at temperatures substantially below those normally maintained by a mammal and may be used in conjunction with hypobaric environments to maintain such partially or completed exsanguinated subjects alive without infusing blood back into the subject.

Abstract: A method for treating a patient suffering from diabetes mellitus by delivering aerosolized insulin to the patient and a programmed, portable, hand-held device used in such treatment methodology is disclosed. Two basic types of drug delivery devices are disclosed for use in connection with the present invention. In accordance with the first type of device the insulin is contained within a low boiling point propellant which is held within a canister under pressure. In accordance with the second type of device the insulin is present within a container in solution and the solution is moved through a porous membrane to create an aerosolized formulation which is inhaled by the patient. In accordance with both devices a measured amount of insulin containing formulation is automatically released into the inspiratory flow path of a patient in response to information obtained from determining the inspiratory flow rate and inspiratory volume of a patient.

Abstract: Antibodies are recovered and isolated from the sera of a number "n" of patients each of which have or have had the same given disease so that each of the "n" patients has, within a large number of different antibodies, some antibodies uniquely associated with the same disease of interest. The antibodies of a first patient are bound to a support surface. To carry out initial screening libraries of molecules are brought into contact with the bound antibodies of the first patient under conditions where binding will occur. Secondary screening is then carried out by extracting and labeling the antibodies of a second patient and using the labeled antibodies to probe the molecules (peptides) isolated in the initial screening. Many of the non-disease specific antibodies (of the second patient) will not bind to the molecules (peptides) of the isolated bacteriophage which bound to the antibodies of the first patient.

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: The presence of clonal macrophages in pre-cancerous and cancerous tissue represents an early stage of the disease in which clonal expansion of macrophages occurs due to HIV integration or other genetic mutation. Clonally expanded macrophages induce proliferation of surrounding tissue leading to cancerous tumor growth. The invention provides methods and kits for diagnosis of HIV- and non-HIV-associated clonal expansion of macrophages in pre-cancerous and cancerous tissue and other cell proliferative diseased tissue. The invention also provides methods for the treatment of cell proliferative diseases induced by clonal macrophage expansion and proliferation of surrounding tissue.

Abstract: Materials immunoreactive with parathyroid hormone-related protein (PTH-rp) are used in the invention method to prevent and treat metastasis and cancer cell growth in bone as well as osteolysis and symptomatic sequelae thereof. Humanized antibodies are included in the invention for application of the invention method to human subjects.

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: 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 preadministration 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: Sulfated oligosaccharides which bind to selectin receptors and act as agonists are formulated into pharmaceutical formulations and administered by injection to treat inflammation. Compounds such as chlorates which act as metabolic inhibitors of carbohydrate sulfation and inhibit the sulfation of naturally occurring ligands for selectin receptors are administered locally by injection to alleviate and/or prevent inflammation. Sulfatase is administered which removes a sulfate moiety from a natural sulfated ligand. The sulfated oligosaccharides can be administered in combination with the chlorates and sulfatases in order to obtain a combined effect which is useful in preventing and/or alleviating inflammation.

Abstract: A protein secreted by peripheral blood mononuclear specifically from CD8.sup.+ lymphocytes is purified and characterized here and designated CD8.sup.+ cell antiviral factor (CAF). The CAF is lipid free and has been found to inhibit the replication of retroviruses and in particular to inhibit the replication of HIV-1, HIV-2, and SIV. CAF can be used to inhibit viral RNA transcription which inhibits viral replication. Accordingly, CAF can be used to treat patients infected with retroviruses. The CAF can also generate antibodies which can be used to create assay devices for detecting CAF in a body fluid and on the surface of CD8.sup.+ cells to determine the condition of an HIV infected individual.

Abstract: The present invention relates to the field of compositions of matter, disclosing compositions of matter which as aqueous solutions, may be used to perfuse a living or non-living subject in need of perfusion. The solutions according to the invention are typified by an aqueous solution comprising a polysaccharide oncotic agent, a physiologically compatible buffer, a simple hexose sugar, dissolved chloride salts of calcium, sodium and magnesium, and a dissolved organic salt of sodium. The solutions according to the invention are effective substitutes for blood. In addition the solution according to the invention may be used to preserve the biological integrity of the organs of a mammalian donor organism as shown by superior anatomical integrity of cryopreserved organs and tissues of subjects perfused with the solution of the invention.

Abstract: Prions are protein based infectious material that cause of variety of diseases such as Scrapie, bovine spongiform encephalopathy (also known as "Mad Cow" disease), Creutzfeldt Jakob Disease, Kuru, and fatal familial insomnia. The invention is directed to artificial prion genes that are made up of elements of the prion genes of a host and test species. When these artificial prion genes are inserted into a transgenic mouse, the resultant mouse becomes susceptible to infection with prions that infect the test species but do not normally infect mice. The transgenic animals are useful for testing for the presence of prions in a sample.

Abstract: A protein secreted by peripheral blood mononuclear cells and specifically from CD8.sup.+ lyphocytes is purified and characterized here and designated CD8.sup.+ cell antiviral factor (CAF). The CAF is lipid free, has a molecular weight of less than 30,000 and has been found to inhibit the replication of retroviruses and in particular to inhibit the replication of HIV-1, HIV-2, and SIV. CAF can be used to inhibit viral RNA transcription which inhibits viral replication. Accordingly, CAF can be used to treat patients infected with retroviruses. The CAF can also generate antibodies which can be used to create assay reagents for detecting CAF in a body fluid and on the surface of CD8.sup.+ cells to determine the condition of an HIV infected individual.

Abstract: A method of treating human patients is provided by the intrapulmonary delivery of a pharmaceutically active peptide formulation. The formulation is automatically released in an aerosolized form 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 the inspiratory flow rate and determining the inspiratory volume of a patient. Reproducible dosing is obtained by providing for automatic release at the same inspiratory flow rate and inspiratory volume each time drug is released. The device includes a timer to enable a patient to take a drug at the same time each day. Further, overadministration of hormone formulations is avoided by providing a pre-programmed microprocessor designed to avoid overdosing.

Abstract: A disposable package, tape, and cassette are provided which makes it possible to hold and disperse therefrom liquid, flowable formulations including aqueous formulations (solutions or dispersions with particles less than 0.25 microns in diameter) of a pharmaceutically active drug. In one embodiment formulation is packaged in individual dosage unit containers which containers are preferably interconnected. The package is designed to be integrated into a cassette which can be loaded into a dispersing device capable of individually opening dosage unit containers and aerosolizing the contents through a porous membrane, into a mouth piece on the cassette, for delivery to a patient. In addition to and alongside of each porous membrane, the package may include one or more openings through which air is forced in order to aid in avoiding the accumulation of aerosolized particles.

Abstract: Strains of HIV-2 capable of infecting humans and non-human primates such as baboons and causing an immune system disease are disclosed. The HIV-2 strain are used to infect non-human primates which infected primates present symptoms of a disease of the immune system and are used to test drugs, e.g., anti-virals and/or vaccines for their ability to treat and/or prevent lentiviral infections such as HIV infections. Useful strains are HIV-2.sub.UC2, HIV-2.sub.UC12 and HIV-2.sub.UC14 and preferred non-human primates are baboons.

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.