Abstract: Disclosed herein are novel methods for preventing or delaying preterm uterine contractions in a pregnant mammal. Also disclosed are novel methods for inducing uterine contractions in a pregnant mammal. In each case, control of uterine smooth muscle contractility is achieved by specifically targeting the MAPK ERK signal transduction cascade. Inactivation of the cascade is disclosed as a novel method for delaying labor. Activation of the MAPK ERK pathway is disclosed as a novel method for inducing labor.

Abstract: The present invention provides an antibody which catalyzes hydrolysis of &bgr;-amyloid at a predetermined amide linkage. The antibody preferentially binds a transition state analog which mimics the transition state adopted by &bgr;-amyloid during hydrolysis at a predetermined amide linkage and also binds to natural &bgr;-amyloid with sufficient affinity to detect by ELISA. Alternatively, the antibody preferentially binds a transition state analog which mimics the transition state adopted by &bgr;-amyloid during hydrolysis at a predetermined amide linkage, and does not bind natural &bgr;-amyloid with sufficient affinity to detect by ELISA. Antibodies generated are characterized by the amide linkage which they hydrolyze. Specific antibodies provided include those which catalyze the hydrolysis at the amyloid linkages between residues 39 and 40, 40 and 41, and 41 and 42, of &bgr;-amyloid.

Abstract: Disclosed are antibodies which catalyze hydrolysis of &bgr;-amyloid. Antibodies generated are characterized by the amide linkage which they hydrolyze. Methods of generating the antibodies by using &bgr;-amyloid peptides which incorporate transition state analogs are also provided. Also disclosed is a vectorized antibody which is characterized by the ability to cross the blood brain barrier, and is further characterized by the ability to catalyze the hydrolysis of &bgr;-amyloid. The vectorized antibody can take the form of a bispecific antibody, which has a first specificity for the transferrin receptor and a second specificity for a transition state adopted by &bgr;-amyloid during hydrolysis.

Abstract: The present invention provides an antibody which catalyzes hydrolysis of &bgr;-amyloid at a predetermined amide linkage. The antibody preferentially binds a transition state analog which mimics the transition state adopted by &bgr;-amyloid during hydrolysis at a predetermined amide linkage and also binds to natural &bgr;-amyloid with sufficient affinity to detect by ELISA. Alternatively, the antibody preferentially binds a transition state analog which mimics the transition state adopted by &bgr;-amyloid during hydrolysis at a predetermined amide linkage, and does not bind natural &bgr;-amyloid with sufficient affinity to detect by ELISA. Antibodies generated are characterized by the amide linkage which they hydrolyze. Specific antibodies provided include those which catalyze the hydrolysis at the amyloid linkages between residues 39 and 40, 40 and 41, and 41 and 42, of &bgr;-amyloid.

Abstract: The present invention provides an antibody which catalyzes hydrolysis of &bgr;-amyloid at a predetermined amide linkage. The antibody preferentially binds a transition state analog which mimics the transition state adopted by &bgr;-amyloid during hydrolysis at a predetermined amide linkage and also binds to natural &bgr;-amyloid with sufficient affinity to detect by ELISA. Alternatively, the antibody preferentially binds a transition state analog which mimics the transition state adopted by &bgr;-amyloid during hydrolysis at a predetermined amide linkage, and does not bind natural &bgr;-amyloid with sufficient affinity to detect by ELISA. Antibodies generated are characterized by the amide linkage which they hydrolyze. Specific antibodies provided include those which catalyze the hydrolysis at the amyloid linkages between residues 39 and 40, 40 and 41, and 41 and 42, of &bgr;-amyloid.

Abstract: Disclosed are methods for the production of second generation catalytic antibodies. The disclosed methods offer a variety of advantages relative to prior art techniques. For example, the methods of the present invention do not require prior identification of the active site of an enzyme, the activity of which is desired in the catalytic antibody. Additionally, the disclosed methods enable the production of antibodies which catalyze chemical reactions which do not occur in nature.

Abstract: The method of the present invention employs a hybrid reagent comprising a first portion (i.e., a cell-targeting portion) which binds to cell surfaces coupled to a second portion (i.e., a toxin-binding portion) which binds to, or has bound to it, an endosomally active domain of DT and releases the endosomally active domain of DT in response to the low pH in endosomal vesicles of cells. Thus, the second portion of the hybrid reagent binds an endosomally active domain directly (e.g., an antibody which binds to all or a portion of the T domain of DT) or indirectly (e.g., an antibody which binds to the R domain of a moiety in which the R domain of DT is coupled to the T domain of DT). A second endosomally active domain of DT, which is different from the first endosomally active domain of DT, is delivered to the same endosomal vesicles separately. The independent endosomally active domains of DT are not toxic to cells until they meet within the endosomes.

Abstract: Disclosed herein is a cell containing a modified peptide. More specifically, the N-terminal amino acid residue of the peptide is modified by the addition of an aryl ketone group which, when contacted with an appropriate substrate, and exposed to light having a wavelength of about 330 nm or greater, results in the covalent bonding of the peptide to the substrate by a C--H insertion dominant mechanism. In preferred, embodiments, the aryl ketone is a benzophenone moiety. The peptide can be designed to specifically bind to a protein of interest in the cell. The cell is then contacted with light having a wavelength of greater than about 330 nm to bind the peptide covalently to the binding site on the intracellular protein of interest. In this way, the modified peptide can be used to specifically and irreversibly block a binding site on an intracellular protein of interest.

Abstract: Hybrid reagents comprising a first portion having an affinity for a cellular target and a second portion having an affinity for a bioactive molecule are described, said hybrid reagents being capable of selectively releasing the bioactive molecule in response to a change in pH. The hybrid reagents of the present invention can be used diagnostically or therapeutically.

Abstract: Hybrid reagents comprising a first portion having an affinity for a cellular target and a second portion having an affinity for a bioactive molecule are described, said hybrid reagents being capable of selectively releasing the bioactive molecule in response to a change in pH. The hybrid reagents of the present invention can be used diagnostically or therapeutically.

Abstract: A homogenous sample of identical bispecific antibody determinants, each determinant being composed of two L-H half-molecules linked by disulfide bonds, each L-H half-molecule being specific for a different antigenic determinant and including at least the F(ab') portion of a monoclonal IgG antibody. The bispecific antibody determinants are useful, e.g., in the formation of multilamellar assemblies and in enzymatic assays.

Abstract: Hybrid reagents comprising a first portion having an affinity for a cellular target and a second portion having an affinity for a bioactive molecule are described, said hybrid reagents being capable of selectively releasing the bioactive molecule in response to a change in pH. The hybrid reagents of the present invention can be used diagnostically or therapeutically.

Abstract: A homogenous sample of identical bispecific antibody determinants, each determinant being composed of two L-H half-molecules linked by disulfide bonds, each L-H half-molecule being specific for a different antigenic determinant and including at least the F(ab') portion of a monoclonal IgG antibody. The bispecific antibody determinants are useful, e.g., in the formation of multilamellar assemblies and in enzymatic assays.

Abstract: This invention pertains to an improved method of inhibiting peroxide-reduction catalytic activity and concomitant toxicity of asbestos and nonasbestos iron-containing silicates. These undesirable reactions can be substantially reduced or essentially eliminated by contacting these potentially harmful materials with an aqueous solution comprising a non-mutagenic non-toxic iron chelating agent, such as phytic acid, diethylenetriamine pentaacetic acid (DTPA) or derivatives of these.

Abstract: A method for extracting collagen from animal collagen-containing tissue using a solution of an organic diamine or amino-alcohol salt. The collagen product has many uses such as cell growth matrices, prosthetic devices, synthetic skin, dressings for wounds, or membranes.

Abstract: A method for extracting collagen from animal collagen-containing tissue using a solution of an organic amine salt. The collagen product has many uses such as cell growth matrices, prosthetic devices, synthetic skin, dressings for wounds, or membranes.

Abstract: Liquified vitreous gel, prepared by a non-extractive technique, has been found to contain a cell proliferation inhibitor whose molecular size is greater than 10,000 daltons. Vitreous isolated from both bovine and chick embryo sources has been found to contain such an activity, which inhibits the growth of endothelial cells prepared from calf aorta. Culture medium conditioned by exposure to calf vitreous hyalocytes (cells found on the periphery of the vitreous gel), is also a source of the high molecular weight inhibitor.The high molecular weight inhibitor is prepared by chromatography of vitreous or hyalocyte-conditioned medium on a column of Bio Gel P-10 or by ultrafiltration. Mateial appearing in the void volume of Bio Gel P-10 (the material whose molecular size is too large to allow it to enter the gel) has a molecular size greater than 13,000 daltons.

Abstract: This invention comprises preparing a cell proliferation inhibitor by a nonextractive method from a tissue which has neither a high content of collagen, nor proteoglycans. The source of inhibitor comprises hyalocyte cells, which release the inhibitor into culture medium. The inhibitor is isolated from the culture medium. By chromatographic separation fractions are provided of varying molecular weight. Fractions both below and above a molecular weight of about 13,000 daltons show inhibitory activity.

Abstract: An inhibitor of endothelial cell growth is prepared by directly liquifying vitreous gel, as for example, forcing vitreous gel through a small orifice so as to directly convert the gel into a liquid, removing insoluble and suspended material and chromatographically fractionating the liquid and isolating the fractions. An inhibitor is also prepared by culturing hyalocyte cells in a medium and chromatographically fractionating the medium.

Abstract: Toxicity of asbestos is reduced by treating it with non-mutagenic non-toxic hydroxamic acid iron-chelating agents.