Abstract: A mutation in the human sonic hedgehog gene is associated with tumorigenesis. A variety of human tumors, including basal cell carcinomas, breast carcinomas, medulloblastomas, etc., have a somatic mutation that results in an amino acid substitution at position 133 ?*his133 SHH!, or in a mutation at position 114. Such mutated genes and fragments thereof, encoded protein, and antibodies specific for the mutated protein are useful in characterizing the phenotype of associated tumors. The mutant protein is useful in drug screening for compositions that antagonize or otherwise modulate HH activity or expression. The encoded protein is also used as a therapeutic, to modulate cell proliferation and differentiation, and treatment of pathological conditions associated with decreased hedgehog signaling.

Abstract: Novel fluorescent heterodimeric DNA-staining energy transfer dyes are provided combining asymmetric cyanine azole-indolenine dyes, which provide for strong DNA affinity, large Stokes shifts and emission in the red region of the spectrum. The dyes find particular application in gel electrophoresis and for labels which may be bound to a variety of compositions in a variety of contexts. Kits and individual compounds are provided, where the kits find use for simultaneous detection of a variety of moieties, particularly using a single narrow wavelength irradiation source. The individual compounds are characterized by high donor quenching and high affinity to dsDNA as a result of optimizing the length of the linking group separating the two chromophores.

Abstract: A disinfectant and cleansing composition is provided in the form of an extruded solid. The active agent in the composition is a halogen-releasing agent such as a halogenated 5,5-dialkylhydantoin. An inert binder such as a fatty acid salt or a hectoritic clay is used to enable manufacture of the composition using an extrusion process. Fragrance, colorants, and other pressure-sensitive materials may be included; fragrance and colorants are preferably incorporated in encapsulated form. Methods for manufacturing the compositions are also provided, as are methods for using the compositions in sanitizing water, particularly in disinfecting and cleansing flush toilets.

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: Human hematopoietic stem cells are provided by separation of the stem cells from dedicated cells. The stem cells may than be maintained by regeneration in an appropriate growth medium. Means are provided for assaying for the stem cells as to their capability for producing members of each of the hematopoietic lineages.

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 number of optically active elements are provided that enable the performance of accurate, dependable chemical analysis in a medium having varying matrix backgrounds and substantial component interferences. Optical transfer cells are provided that include positive correlation filter systems adapted to accept near-IR radiation and to pass a wavelength from that radiation having high correlation with a particular analyte. A near-IR spectrometer apparatus for the measurement of analyte concentration in a complex medium is also provided. The apparatus features an optical transfer cell constructed according to the invention. The apparatus can be used in the non-invasive determination of blood analyte concentrations in a variety of mediums. Methods of measuring the concentration of a blood analyte in a mammalian subject are also provided. The methods entail the use of reflective near-IR radiation to interrogate a medium to obtain spectrally modified radiation.

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 concentration of an analyte present in a sample is determined using multi-spectral analysis in the near infrared range. Incident radiation containing a plurality of distinct, nonoverlapping regions of wavelengths in the range of approximately 1100 to 3500 nm is used to scan the sample. Diffusively reflected radiation emerging from the sample is detected, and a value indicative of the concentration of the analyte is obtained using an application of chemometrics techniques. Information obtained from each nonoverlapping region of wavelengths can be cross-correlated to remove background interferences.

Abstract: Benzothiophene analogs useful to treat herpes viral infections, particularly cytomegalovirus, are provided. These antiviral agents have the structural formula (I) ##STR1## wherein R and R.sup.1 are as defined herein, and may be in free base or acid addition salt form. Pharmaceutical compositions are provided containing the antiviral agents, as are methods of treating herpes-infected individuals.

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: 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: The use of individual or combinations of cytokines, particularly IL-3, GM-CSF, and c-kit ligand are employed for long-term hematopoiesis in serum free culture in the absence of stromal cells. The cultures can be used for evaluating compounds and their effect on hematopoiesis, particularly as to lifetime and nature of differentiation. In addition, the expanded cells may be used for engraftment in a mammalian host or enhancement of particular cell lineages in a mammalian host. The subject systems may be used with any mammalian hemopoietic cells, but finds particular application with primates, more particularly humans.

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: The present invention features packaging cell lines and recombinant retroviral particles produced thereby, particularly pseudotyped retroviral particles. Preferably, the packaging cell lines are derived from HeLa, Cf2Th, D17, MDCK, or BHK cells, most preferably from Cf2Th cells. Retroviral particles are produced by inducibly expressing an envelope protein of interest (e.g., a retroviral envelope or the envelope protein of vesicular stomatitis virus (VSV G)). Inducible expression of the envelope protein is accomplished by operably linking an envelope protein-encoding nucleotide sequence to an inducible promoter (e.g., a promoter composed of a minimal promoter linked to multiple copies of tetO, the binding site for the tetracycline repressor (tetR) of the Escherichia coli, tetracycline resistance operon Tn10).

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: 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 ratiometric optical sensors method of making is provided to measure dissolved oxygen in a fluid sample. The sensor is formulated so as to contain an oxygen permeable membrane of a cured perfluorinated urethane polymer and, incorporated therein, an oxygen-sensitive indicator component and a reference dye component. The emission spectrum from the indicator component is calibrated by comparison with that of the reference dye, which is substantially less sensitive to oxygen-quenching and which has a photodecomposition rate similar to the indicator component. Methods for making and using the membrane and sensor are provided as well.

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.