Abstract: Methods and products for inducing IL-2 secretion, inducing IL-10 secretion, activating T cells, suppressing IgG antibody response to specific antigen, promoting allograft survival, reducing postoperative surgical adhesion formation, and protecting against abscess formation associated with surgery, trauma or diseases that predispose the host to abscess formation are provided. The methods of the invention are accomplished using an immunomodulator which is a polymer having at least two repeating charge motifs separated by at least a certain minimum distance.

Abstract: The present invention provides binding moieties for fibrin which have a variety of uses wherever detecting, isolating or localizing fibrin, and particularly fibrin as opposed to fibrinogen, is advantageous. Particularly disclosed are synthetic, isolated polypeptides capable of binding fibrin and recognizing the form of polymerized fibrin found in thrombi. In addition, the polypeptides have a slow dissociation rate from fibrin, which improves their ability to form a contrast image at the site of a fibrin clot, making the disclosed binding moieties particularly useful as imaging agents for thrombi.

Abstract: The present invention relates to polymeric nanoparticles, particularly useful in drug and agent delivery, as well as for imaging and diagnosis. The polymeric nanoparticles of the present invention comprise cross-linkers that, when degraded, leave simple linear polymeric molecules that can be excreted by the body. The present invention also relates to methods of producing the polymeric nanoparticles of the present invention, and methods of using them in drug and agent delivery, as well as imaging and diagnosis.

Abstract: The present invention includes PG polymer complexes with paramagnetic materials, such as Gd, Mn and iron oxide. The complexes may also include chelating agents which may be covalently attached to the PG polymer backbone through linkers. PEG may also be attached to the PG polymer backbone. The complexes may include targeting molecules. The complexes are useful as MRI contrast agents, particularly as blood pool agents.

Abstract: Cascade polymers, containing complex-forming ligands, optionally at least five ions of an element of atomic numbers 21-29, 39, 42, 44 or 57-83, as well as, if desired, cations of inorganic and/or organic bases, amino acids or amino acid amides, are valuable complexing compounds and complexes for diagnostics and therapy.

Abstract: The present invention provides a coating that emits magnetic resonance signals and a method for coating medical devices therewith. The coating includes a paramagnetic metal ion-containing polymer complex that facilitates diagnostic and therapeutic techniques by readily visualizing medical devices coated with the complex.

Abstract: The present invention relates to a vascular embolic material for use in the treatment of an angiotropy of various tumors and a vascular malformation. Specifically, the present invention relates to a vascular embolic material having the specific morphological, physicochemical and radiological characteristics and multifunction in the form of a bead or a sponge comprising a mixture of a hydrophilic polymer material and a metal material. The specific physicochemical and radiological characteristics of the vascular embolic material according to the present invention facilitate its clinical use and aid in the diagnosis before and after the embolization. Further, a local radiation treatment and anticancer treatment is possible and thus the therapeutic effect on said disorders can be enhanced.

Abstract: Peptides and peptide-targeted multimeric contrast agents are described, as well as methods of making and using the contrast agents.

Abstract: An improved contrast agent for magnetic resonance imaging comprises particles to each of which is coupled a multiplicity of chelating agents containing paramagnetic ions. In the improved agent, the position of the ion is offset from the surface of the particle so as to improve the relaxivity imparted by the contrast agent.

Abstract: This invention relates to a method and system for improving diagnostic imaging and/or delivering therapeutically active agents for control of hyperlipidemia and infectious diseases (bacterial or viral), comprising nanoscale block copolymer assemblies carrying drug molecules in its core and receptor peptide in the corona surrounding the core, forming larger micelle or vesicle aggregates with target molecules such as LDL molecules and surface lipid of microorganisms.

Abstract: Macromolecular imaging agents comprising a polyalkylenimine dendrimer conjugated to a metal chelate are disclosed. In particular embodiment, the imaging agent is a diaminobutane-core polypropylenimine dendrimer having surface amino groups conjugated to gadolinium metal chelates. Administration of this gadolinium conjugate to a subject permits visualization of liver micrometastases as small as about 0.3 mm in a magnetic resonance image of the subject's liver.

Abstract: The invention relates to novel magnetic resonance imaging contrast agents and methods of detecting physiological signals or substances.

Abstract: Magnetic resonance (“MR”) contrast-enhancing agents comprise poly(amino acid) backbone chain conjugated to chelating moieties that comprise a plurality of carboxylic acid groups that form coordination complexes with paramagnetic ions. A method for detecting atherosclerotic plaque areas comprises administering at least one of these contrast agents into a subject; and obtaining and comparing MR images of and MR signals from the plaque areas before and after administering the contrast agent. The method can be used to assess an effectiveness of a prescribed course of treatment for atherosclerosis.

Abstract: The present invention relates to novel compositions comprising microspheres and/or nanospheres containing condensed polyanionic bioactive agents, such as DNA. The polyanionic bioactive agent in the microspheres and/or nanospheres is preferably condensed using a polycationic condensing agent, such as poly-L-lysine. The present invention further relates to methods for producing the microspheres and/or nanospheres containing condensed polyanionic bioactive agents.

Abstract: The present invention relates to a composition that includes gadolinium particles encapsulated in microsphere shells. The composition is suitable for use as a contrast agent with a plurality of imaging modalities, including, for example, ultrasound, magnetic resonance imaging, and computed temography. The compositions also are useful for therapeutic applications, including neutron capture therapy.

Abstract: Cascade polymer complexes that contain

Abstract: Recombinant fragments of Factor C are disclosed. These proteins and peptides show great potency in recognizing, binding to, neutralizing and removing endotoxin. These molecules can thus be used for anti-microbial, anti-endotoxin, and anti-sepsis therapy. SSCrFCES is a 38 kDa protein representing the LPS-binding domain of Factor C. The ability of SSCrFCES to bind lipid A was analyzed using an ELISA-based assay as well as surface plasmon resonance. Surface plasmon resonance similarly carried out for SSCrFC-sushi-1,2,3-GFP, SSCrFC-sushi-1GFP, and SSCrFC-sushi-3GFP confirmed their superior affinity for endotoxin. The 50% endotoxin-neutralizing concentration of SSCrFCES against 200 EU of endotoxin is 0.069 &mgr;M, suggesting that SSCrFCES is an effective inhibitor of LAL coagulation cascade.

Abstract: Small dendrimer-based MRI contrast agents are disclosed to accumulate in renal tubules. The accumulation enables visualization of renal structure and function, permitting assessment of structural and functional damage to the kidneys. In a disclosed embodiment, six, small dendrimer-based MRI contrast agents were synthesized, and their pharmacokinetics, whole body retention, and renal MRI images were evaluated in mice. Surprisingly, despite having unequal renal clearance properties, all of the dendrimer agents clearly visualized the renal anatomy and proximal straight tubules of the mice better than Gd-[DTPA]-dimeglumine. Dendrimer conjugate contrast agents prepared from PAMAM-G2D, DAB-G3D, and DAB-G2D dendrimers were excreted rapidly and may be acceptable for use in clinical applications.

Abstract: The present invention relates to contrast agents for diagnostic imaging. In particular, this invention relates to novel multimeric compounds which exhibit improved relaxivity properties upon binding to endogenous proteins or other physiologically relevant sites.

Abstract: The present invention provides methods of targeting breast cancer, prostate cancer, pancreatic cancer or melanoma cells using ST peptides. These methods permit both diagnostic evaluation and therapeutic intervention using appropriate conjugates.

Abstract: Cascade polymers, containing complex-forming ligands, optionally at least five ions of an element of atomic numbers 21-29, 39, 42, 44 or 57-83, as well as, if desired, cations of inorganic and/or organic bases, amino acids or amino acid amides, are valuable complexing compounds and complexes for diagnostics and therapy.

Abstract: In certain aspects the present invention provides methods and compositions related to contrast agents for magnetic resonance imaging. In certain variations, contrast agents provided herein are generated in situ via genetic instructions and become potent upon sequestering available metal atoms. Exemplary contrast agents include metal-binding proteins.

Abstract: The present invention provides a controllably degradable cationic polymer for delivery of biomolecules (nucleic acids, peptides, etc.), drugs, molecules used in medical imaging applications, sensitizing agents used in cancer treatments, and molecules used in tissue engineering. The present invention also provides a method for synthesizing the polymer according to the present invention.

Abstract: An improved contrast agent for magnetic resonance imaging comprises particles to each of which is coupled a multiplicity of chelating agents containing paramagnetic ions. In the improved agent, the position of the ion is offset from the surface of the particle so as to improve the relaxivity imparted by the contrast agent. A tether offsetting the chelate from the surface of the particle may optionally contain cleavage sites permitting more facile excretion of the chelated paramagnetic ion.

Abstract: The invention relates to super-paramagnetic single domain particles with increased R1 relaxivity and with surface-stabilizer substances. The particles are characterized in that they consist of iron hydroxide, ferric hydrate, iron oxide, iron mixed oxide or iron; are between 1 and 10 nm in size, the mean particle diameter d50 being 2-4 nm; and have increased R1 relaxivity of between 2 and 50, the ratio of the relaxivities R2/R1 being less than 5. Stabilizer substances of special carboxylic acids are bound to the particle surfaces; these prevent aggregation and sedimentation under gravity or in a magnetic field. If necessary, the particles can also contain further known stabilizer substances and other pharmacological substances. The novel particles can be used for attacking tumors, boosting immunity, for cell fusion, gene transfer, or as contrasting agents in magnetic resonance diagnostics using magnetic fields where necessary.

Abstract: A method of making fine dry particles of substances is provided by forming a composition comprising a substance of interest and a supercritical or near critical fluid; rapidly reducing the pressure on said composition, whereby droplets are formed; and passing said droplets through a flow of heated gas. The process does not require any organic solvent.

Abstract: The present invention relates generally to the field of prothrombin time reagents for determining dysfunction in the coagulation system and more specifically to reagents made from native thromboplastin or purified or recombinant tissue factor and phospholipids from a natural or synthetic source. The present invention relates to methods to make a diagnostic reagent that includes a membrane-bound protein incorporated into a liposome and having additional empty liposomes (liposomes without membrane-bound protein incorporated therein) added to the solution.

Abstract: A method of producing a diagnostic or therapeutic conjugate of a protein, polypeptide or peptide containing at least one disulfide bond which is necessary to maintain its biological activity, and bearing at least one thiol-containing moiety linked thereto through a hydrazone or hydrazine linkage, is effected by contacting said protein, polypeptide or peptide with a thiol-reactive diagnostic or therapeutic agent, either preformed or generated in situ, to form a stable diagnostic or therapeutic conjugate of the protein, polypeptide or peptide without substantial cleavage of the disulfide bond. Diagnostic and therapeutic conjugates produced using the foregoing method, as well as kits for carrying out the method are provided.

Abstract: The present invention relates to iron-containing nanoparticles having a modular structure, their production, and their use for diagnostic and therapeutic purposes. The nanoparticles according to the invention are characterized in that they consist of an iron-containing core, a primary coat (synthesis polymer), and a secondary coat (targeting polymer) and, optionally, of pharmaceutic adjuvants, pharmaceuticals, and/or adsorption mediators/enhancers.

Abstract: The present invention relates to polynucleotide and polypeptide molecules for zsig51, a novel member of the cystine knot family of polypeptides. The polypeptides comprise a sequence of amino acid residues that is at least 80% identical in amino acid sequence to residues 1 through 106 of SEQ ID NO:2. The invention further provides therapeutic and diagnostic methods utilizing the polynucleotides, polypeptides, and antagonists of the polypeptides.

Abstract: The invention relates to a device for magnetic separation of pharmaceutical preparations, their starting or intermediate products that contain a separation space, in which a magnetic gradient field prevails and which has an inlet and an outlet, whereby the device is embodied in the form of an attachment filter for injection instruments or infusion instruments.

Abstract: The invention relates to injectable compositions for increasing the image contrast between specific organ areas in the magnetic resonance imaging (MRI) of human and animal patients. This enables better differentiation of neighboring tissue portions. Methods of the preparation of such compositions and their use in the MRI of living subjects are also disclosed.

Abstract: A method of stimulating polymerization of a tau protein, comprising the step of contacting said protein with a fatty acid. In another embodiment of the present invention, there is provided a method of stimulating polymerization of a amyloid peptide, comprising the step of contacting said peptide with a fatty acid.

Abstract: Methods of modifying polypeptide drugs in order to enhance their transdermal electrotransport flux are provided. The polypeptide is modified by substituting a histidine residue (His) for one or more glutamine (Gln), threonine (Thr) and/or asparagine (Asn) residue(s). The His for Gln substitution is particularly preferred from the standpoint of retaining biological activity of the parent polypeptide. Compositions containing the modified polypeptide, which are useful for transdermal electrotransport delivery, are also provided.

Abstract: The present invention relates to capsules encapsulating antibody-producing cells, and to use of such capsules and encapsulated cells, respectively, for implantation in vivo for long term delivery or sustained delivery of antibodies of therapeutic interest.

Abstract: The invention relates to MR contrast media containing composite nanoparticles, preferably comprising a superparamagnetic iron oxide core provided with a coating comprising an oxidatively cleaved starch coating optionally together with a functionalized polyalkyleneoxide which serves to prolong blood residence.

Abstract: The active, galactose binding site of proteins associated with metastatic tumor cells has been identified and sequenced. The polypeptide comprising the active site may be used as an immunotherapeutic agent. Identification of the site makes possible an in vivo diagnostic assay for metastatic cell as well as therapeutic methodologies and materials.

Abstract: Compositions comprising an admixture of a biofunctional polymer substrate and a biofunctional material substrate adapted for use in or in association with the human or animal body, cultivated or uncultivated living matter and methods for making and using thereof are disclosed. The biofunctional material substrate retains bioactivity in the admixture. As disclosed, the compositions may be made by a process which comprises contacting a mixture of the substrates or their precursors with a supercritical fluid under supercritical conditions of reduced viscosity to plasticise and swell the biofunctional polymer substrate and under conditions of physical blending to distribute the biofunctional material substrate throughout the biofunctional polymer substrate, and releasing the supercritical fluid under subcritical conditions. Also disclosed are biofunctional polymer matrices and methods of making and using thereof.

Abstract: Agents containing magnetic particles are suitable for use in enhancing images in diagnostic procedures, e.g., via x-ray, ultrasound or especially NMR. Preferred particles are based on metals, e.g., iron, cobalt or nickel, double metal oxides/hydroxides or complexes thereof.

Abstract: The invention describes improved methods for incorporating nucleic acids into polymeric microspheres and/or nanospheres through the use of a condensing agent.

Abstract: This relates to a contrast medium containing a complex of a gadolinium (Gd) type contrast agent and a polymer. More particularly, the contrast medium wherein the polymer capable of phase transit in response to environmental changes, particularly, pH, light or temperature, to develop a different water solubility, and a method for imaging by the use of this contrast medium. By binding a polymer responsive to microenvironmental changes with a Gd type MRI contrast agent, on-off switching of MRI imaging capability is enabled, wherein imaging occurs only on the target sites. Consequently, a highly specific MRI contrast medium can be obtained, whereby a highly specific MRI diagnosis is made possible, wherein only the target sites such as a tumor and a particular site are imaged and otherwise at the site where imaging is not necessary.

Abstract: This invention relates to a method of contrast agent-enhanced magnetic resonance imaging of perfusion in vasculated tissue within a human or non-human animal body in which a bolus comprising a contrast-enhancing amount of a magnetic resonance imaging contrast agent is administered into the vascular system of said body, and said body is subjected to a magnetic resonance imaging procedure whereby signals or images representative of first pass of said contrast agent bolus through tissue of interest are generated, characterised in that (i) said contrast agent is capable of exhibiting simultaneous, determinable T1 and T2* reducing effects under the imaging procedure employed and (ii) a T1-weighted imaging procedure is used (a) to visualise the first pass of said contrast agent bolus through said tissue by virtue of its signal lowering T2* effect and (b) to obtain a T1-weighted contrast agent-enhanced image of said tissue.

Abstract: The present invention provides an integrated structural unit that includes a diagnostic form that includes at least one active ingredient that is present in an amount that advantageously does not vary by more than about five percent from a predetermined target amount. In one embodiment, the unit form comprises a substrate, a deposit that is disposed on the substrate, and a spreading layer that overlies the deposit and is used to retain and spread a sample of liquid which is to be assayed. The deposit comprises a powder, including the active ingredient(s). The diagnostic form is created via a dry powder deposition apparatus that electrostatically deposits the powder on the substrate utilizing an electrostatic chuck and charged powder delivery apparatus.

Abstract: The use of electroactive materials having regions of high electron density as contrast agents in magnetic resonance imaging is described. The electroactive materials may be electroactive polymers, inorganic clusters, carbon clusters, molecules that inherently exhibit electron donor-acceptor behavior having regions or moieties of high electron density, or any combination of the abovementioned contrast agents. The contrast agents of the invention decrease relaxation times of water when introduced into a subject for magnetic resonance imaging. It is particularly preferred that the contrast agents be introduced in the form of a colloidal suspension.

Abstract: Novel gas filled microspheres useful as magnetic resonance imaging (MRI) contrast agents are provided.

Abstract: The instant invention provides a biodegradable tell-tale composition which is applied cutaneously or subcutaneously to a human or animal subject for aiding in the determination of instillation or application of a medicament, vaccine or the like; and furthermore for providing, via the biodegradable functionality, a useful tool for measuring the period of time which has passed since the most recent inoculation.

Abstract: The invention relates to novel nucleic acid fragments encoding polypeptides which are capable of mediating contact between enamel and cell surface. The invention also relates to expression vectors containing the nucleic acid fragments according to the invention for production of the protein, organisms containing said expression vector, methods for producing the polypeptide, compositions comprising the polypeptides, antibodies or antibody fragments recognizing the polypeptides, and methods for treating various hard tissue diseases or disorders.

Abstract: Disclosed are compositions suitable for use in embolizing blood vessels which compositons comprise a cellulose diacetate polymer, a biocompatible solvent and a water insoluble contrasting agent selected from the group consisting of tantalum, tantalum oxide, and barium sulfate. Also disclosed are methods for embloizing a blood vessel using the compositins described herein.

Abstract: Microparticulate contrast agents comprising gas or a gas precursor encapsulated by a non-polymeric and non-polymerisable wall-forming material are readily characterisable materials exhibiting surprising structural integrity and stability.

Abstract: The present invention pertains to an image enhancing agent having a polymeric core including an image-enhancing compound chemically bound thereto and a polymeric shell surrounding the core and compound. The agent may be used for enhancing MRI images, by introducing gadolinium or other appropriate material into the core. Generally, the core is formed from an acid monomer and an esterified monomer. Preferably, a cross-linking monomer is included in the core.