Abstract: Methods and compositions relating to chimeric genes containing (i) a tissue-specific promoter and (ii) a hypoxia response enhancer element, both of which are operably linked to a selected gene, such as a reporter gene, therapeutic gene (e.g., bcl-2, NOS, catalase and SOD), or deleterious gene are disclosed. Expression of the selected gene is enhanced in the target tissue under hypoxic conditions, such as conditions encountered during episodes of ischemia and reperfusion. The methods and compositions may be used as therapeutics and/or diagnostics.

Abstract: A method of diagnosing a patient is carried out by delivering an aerosolized dose of a radioactive formulation to a patient and making a ventilation image of radioactive material deposited in the lung. This image is compared with a separately generated image (perfusion image) taken after injecting radiolabled particles into the pulmonary arterial circulation. Devices, packaging and methodology for creating aerosols are provided which allow for efficient and repeatable delivery of radioaerosols to the lungs of a patient. Devices may be plug-in units or hand-held, self-contained units which are automatically actuated at the same release point in a patient's inspiratory flow cycle. The device is loaded with a container of a radioactive formulation such as .sup.99m Tc-labelled diethylene-triamine pentaacetic acid (DTPA). Actuation of the device forces the radioactive formulation 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.

Abstract: A device, drug package and methodology for using such to generate an aerosol by moving a flowable formulation through a low resistance filter and then through a nozzle comprised of a porous membrane are disclosed. The package is comprised of a collapsible wall portion that forms a container for holding a liquid formulation which container has an opening covered by a cover portion comprising a nozzle. The membrane pores of the nozzle have a size in the range of 0.25 to 6 microns, preferably 0.5 to 6 microns. A low resistance filter, which is positioned between the flowable formulation and the nozzle, includes openings that are the same size as or smaller than the pores of the nozzle's porous membrane but includes the openings in an amount and density such that flowable formulation flows through the filter with less resistance than when the formulation moves through the porous membrane.

Abstract: A mutated form of human P-glycoprotein (mdr1.DELTA.F335/336) is identified, consisting of a single or double codon deletion (Phe335 and/or 336) in the TM region of P-gp. The mdr1.DELTA.F335/336 encoded P-glycoprotein is characterized by an altered spectrum of cross-reactivity to cytotoxins and resistance to modulation by cyclosporins, with a loss of the capacity to bind or transport cyclosporine, PSC 833, and vinblastine. These data demonstrate that cyclosporine, PSC 833, vinblastine, Rh-123, and dactinomycin share at least one binding domain on, which plays an important role in the interaction of P-gp with modulators. The nucleic acid compositions encoding mdr1.DELTA.F335/336 find use in gene therapy to transfer modulator-resistant multidrug resistance into transfected cells; to produce the encoded protein for functional mapping studies, and in studying associated physiological pathways.

Abstract: A method for measuring the concentration of a chemical present in a blood stream of a mammalian subject is disclosed. The method involves contacting the subject's skin with a sensor assembly comprised of an ionically conducting material which contacts the skin, a working electrode which is in contact with the ionically conducting material which electrode has a catalytic surface and a mask having an opening therein. The mask is positioned between the skin and the working electrode. When the electrode is activated, chemical is transported through the skin and the ionically conductive material. The mask is positioned so that it blocks the flow into the catalytic surface except for flow which is substantially axially to the catalytic surface. Electrical signal generated at the working electrode is monitored over a period of time and correlated with a concentration of chemical present in the blood stream of the mammalian subject.

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, methods of making BH55 hyaluronidase polypeptides, and antibodies that specifically bind BH55.

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 present invention provides glucans and derivatives thereof which are useful as raw materials in the starch processing industries, food and drink compositions, food additive compositions, and starch substitutes for biodegradable plastics, and processes for preparing the same. Particularly, it provides glucans and derivatives thereof having excellent properties such as higher solubility in water than conventional starches, lower viscosity and the glucans are not subject to retrogradation which is observed in conventional starches, and which are capable of preventing the retrogradation of starches.

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: A method is provided for preventing erectile dysfunction, particularly vasculogenic impotence, in a male individual. The method involves periodic administration of a vasoactive agent throughout a 24-hour period. The agent and dosage regimen are selected such that regularly increased blood flow to the penis is achieved, in turn preventing arterial occlusion and vascular deterioration of the muscular fibers of the vessels and collagen fibers of the cavernosal tissue.

Abstract: A method of treating patients suffering from a respiratory disease using a programmable, hand-held, self-contained drug dispensing device is disclosed. A patient's inspiratory flow rate is measured and a determination is made of a typical and preferred rate and volume for the release of respiratory drug. To obtain repeatability in dosing the drug is repeatedly released at the same rate and volume. To maximize the amount of drug delivered based on the amount released the drug is released at a rate of from about 0.10 to about 2.0 liters/second and (2) a volume of about 0.15 to about 0.8 liters. Parameters such as rate, volume, and particle size of the aerosolized formulation are adjusted to obtain repeatable dosing of the maximum amount of drug to the desired area of the lung. Lung function is measured and use parameters are adjusted in order to improve lung function.

Abstract: This invention encompasses a method for inhibiting vascular cellular activity of cells associated with vascular lesion formation in mammals which involves administering an effective dosage of at least one antisense sequence to at least one gene expressing a cyclin or a cyclin dependent kinase which inhibits the expression of the gene. More particularly, the invention involves administering antisense sequences which inhibit the expression of cyclin A, B1, B2, C, D1, D2, D3, E or cyclin X (p46) cyclin X and cyclin dependent kinase cdc2, cdk2, cdk4 or cdk5. It is preferable to use two antisense sequences each from a different cyclin or cyclin dependent kinase. The cyclin or cyclin kinase depending kinase dosage is preferable administered in combination with proliferating cell nuclear antigen (PCNA). Antisense methods and compositions direct to inhibiting the expression of growth factors such as TGF-.beta..sub.1, TGF, bFGF, PDGF are also contemplated by the present invention.

Abstract: A transgenic, non-human animal is provided which overexpresses a gene responsible for the accumulation of monocytes and leukocytes. The animal is preferably a mammal and more preferably a mouse, rat or guinea pig. The transgenic animal is created by artificially inserting a transgene into a fertilized egg of the animal which egg is then inserted within a pseudo pregnant female where it is allowed to grow. The transgene preferably expresses human Monocyte Chemoattractant Protein-1 (MCP-1) and more preferably overexpresses MCP-1 in type II pulmonary epithelial cells. The invention includes DNA constructs and vectors containing the constructs with a particularly preferred vector being SPC-MCP-1. The plasmid SPC-MCP-1 includes a promoter operatively linked to a human MCP-1 coding sequence. The transgenic animal provides a useful animal model for testing drugs for their efficacy with respect to the treatment of diseases and conditions which result in an acceptable high accumulation of monocytes and/or lymphocytes.

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: Sets of fluorescent energy transfer labels and methods for their use in multi component analysis, particularly nucleic acid enzymatic sequencing, are provided. In the subject sets, at least two of the labels are energy transfer labels comprising a common donor and acceptor fluorophore in energy transfer relationship separated by different distances and capable of providing distinguishable fluorescence emission patterns upon excitation at a common wavelength. The subject labels find particular use in a variety of multi-component analysis applications, such as probes in FISH and multi array analyses, as well as primers in nucleic acid enzymatic sequencing applications.

Abstract: TSG101 is a tumor susceptibility gene whose homozygous functional knock out in fibroblasts leads to transformation and the ability of these cells to form metastatic tumors in nude mice. The cellular transformation that results from inactivation of TSG101 is reversible by restoration of TSG101 function. Decreased expression of TSG101 is associated with the occurrence of certain human cancers, including breast carcinomas. The TSG101 nucleic acid compositions find use in identifying homologous or related proteins and the DNA sequences encoding such proteins; in producing compositions that modulate the expression or function of the protein; and in studying associated physiological pathways. In addition, modulation of the gene activity in vivo is used for prophylactic and therapeutic purposes, such as treatment of cancer, identification of cell type based on expression, and the like.

Abstract: Sets of fluorescent energy transfer labels and methods for their use in multi component analysis, particularly nucleic acid enzymatic sequencing, are provided. In the subject sets, at least two of the labels are energy transfer labels comprising a common donor and acceptor fluorophore in energy transfer relationship separated by different distances and capable of providing distinguishable fluorescence emission patterns upon excitation at a common wavelength. The subject labels find particular use in a variety of multi-component analysis applications, such as probes in FISH and multi array analyses, as well as primers in nucleic acid enzymatic sequencing applications.

Abstract: Three classes of GFP mutants having single excitation maxima around 488 nm are brighter than lid-type GFP following 488 nm excitation. GFPmut1 has a double substitution: F64L, S65T; GFPmut2 has a triple substitution: S65A, V68L, S72A; and GFPmut3 is characterized by the double substitution S65G, S72A. The excitation maxima of the three mutants are at 488 nm, 481 nm and 501 nm respectively. The fluorescence intensities following excitation at 488 nm are an order of magnitude higher than that of wild-type GFP excited at 488 nm in E. coli. The expression of GFP is observable minutes after induction.

Abstract: Composition for and method of stimulating growth of plants, e.g. increase in crop production. The composition comprises a carbon skeleton/energy component, typically a sugar or mixture of sugars; a macronutrient component providing the elements nitrogen, phosphorus, potassium and calcium, preferably also magnesium and sulfur; a micronutrient component providing zinc, iron and manganese, preferably also copper, boron, molybdenum and cobalt. The composition also preferably contains a vitamin/cofactor component and an enhancement component. The composition may be in the form of an aqueous solution or in a form suitable for coating seeds or coating pollen. It may be applied as a foliar spray, as a soil amendment, as a root dip or as an injectable solution. Preferably where, for example, it is used as a foliar spray it is applied at intervals at different stages of growth.

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 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). A PrP gene of the host is preferably manipulated to include a mutation which matches a mutation which causes prion disease in the genetically diverse mammal. 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.