Abstract: A method for alleviating the symptoms of a cosmetic or dermatologic skin condition is described. An effective amount of a poly(hydroxy acid)/polymer conjugate in a pharmaceutically or cosmetically acceptable vehicle is provided. Topical compositions of the conjugates with another cosmetic or dermatological agent, and compounds of the conjugates having attached physiologically active functional groups, are also provided.

Abstract: A method for identifying a microorganism having a reduced adaptation to a particular environment comprising the steps of:(1) providing a plurality of microorganisms each of which is independently mutated by the insertional inactivation of a gene with a nucleic acid comprising a unique marker sequence so that each mutant contains a different marker sequence, or clones of the said microorganism;(2) providing individually a stored sample of each mutant produced by step (1) and providing individually stored nucleic acid comprising the unique marker sequence from each individual mutant;(3) introducing a plurality of mutants produced by step (1) into the said particular environment and allowing those microorganisms which are able to do so to grow in the said environment;(4) retrieving microorganisms from the said environment or a selected part thereof and isolating the nucleic acid from the retrieved microorganisms;(5) comparing any marker sequences in the nucleic acid isolated in step (4) to the unique marker sequ

Abstract: External guide sequence (EGS) molecules for eukaryotic RNAse P are engineered to target efficient and specific cleavage of target RNA. Engineered RNA molecules are designed and synthesized which contain specific nucleotide sequences which enable an external guide sequence for RNAse P to preferentially bind to and promote RNAse P-mediated cleavage of target RNA molecules. Short External Guide Sequence (SEGS) molecules have been constructed that, when hybridized to a target molecule, provide a minimal structure recognized as a substrate by RNAse P. The SEGS/target structure is comprised of a structures similar to the A stem and the T stem of a tRNA, the natural substrate of RNAse P. The SEGS makes up only half of these stem structures. The other half of the stem structures is provided by the target molecule. By allowing the target molecule to form more of the RNAse P substrate structure, the disclosed SEGS molecules can be significantly smaller than previous EGS molecules.

Abstract: Improved aerodynamically light particles for drug delivery to the pulmonary system, and methods for their synthesis and administration are provided. In a preferred embodiment, the aerodynamically light particles are made of a biodegradable material and have a tap density less than 0.4 g/cm.sup.3 and a mass mean diameter between 5 .mu.m and 30 .mu.m. The particles may be formed of biodegradable materials such as biodegradable polymers. For example, the particles may be formed of a functionalized polyester graft copolymer consisting of a linear .alpha.-hydroxy-acid polyester backbone having at least one amino acid group incorporated therein and at least one poly(amino acid) side chain extending from an amino acid group in the polyester backbone. In one embodiment, aerodynamically light particles having a large mean diameter, for example greater than 5 .mu.m, can be used for enhanced delivery of a therapeutic agent to the alveolar region of the lung.

Abstract: Solid free-form techniques for making medical devices for controlled release of bioactive agent and implantation and growth of cells are described using computer aided design. Examples of SFF methods include stereo-lithography (SLA), selective laser sintering (SLS), ballistic particle manufacturing (BPM), fusion deposition modeling (FDM), and three dimensional printing (3DP). The macrostructure and porosity of the device can be manipulated by controlling printing parameters. Most importantly, these features can be designed and tailored using computer assisted design (CAD) for individual patients to optimize therapy.

Abstract: Variant complement proteins that are modified in their complement-mediated activity are provided, along with methods for their preparation, and their potential uses. The modifications comprise amino acid substitutions in regions of the complement proteins that contain certain motifs also present in homologous proteins. The amino acid substitutions and their effect on the complement activity of the modified protein are also provided.

Abstract: It has been discovered that any RNA can be targeted for cleavage by RNase P from prokaryotic or eukaryotic cells using a suitably designed oligonucleotide ("external guide sequence", or EGS) to form a hybrid with the target RNA, thereby creating a substrate for cleavage by RNase P in vitro. The EGS hydrogen bonds to the targeted RNA to form a partial tRNA like structure including the aminoacyl acceptor stem, the T stem and loop, and part of the D stem. An EGS can be modified both by changes in sequence and by chemical modifications to the nucleotides. The EGS can be a separate molecule or can be combined with an RNase P catalytic RNA sequence to form a single oligonucleotide molecule ("RNase P internal guide sequence" or RIGS). Methods are also disclosed to randomly select and to express a suitable EGS or RIGS in vivo to make a selected RNA a target for cleavage by a host cell RNase P or introduced RIGS, thus preventing expression of the function of the target RNA.

Abstract: Provided are biodegradable microparticles, which exhibit a linear release profile of active agent, and methods for making the microparticles. The microparticles include a mixture of a biodegradable polymer, a water soluble polymer, and an active agent. Preferred biodegradable polymers include lactide homopolymers or copolymers of lactide and glycolide, and preferred water soluble polymers include poly(ethylene glycol) (PEG) or PEG copolymers. The microparticles are made using an emulsion/solvent extraction method, in which the continuous phase of the secondary emulsion contains an organic solvent that is miscible with the organic solvent in the primary emulsion.

Abstract: The invention concerns methods for the production of in vitro constituted biological materials and their subsequent use as implants for healing cartilage and bone defects. A biological composite (28) comprising periosteum (22) and cartilage or bone forming cells (26) is described as well as an in vitro cultured periosteum.

Abstract: The membrane permeating antibacterial peptide, PR-39, previously found only in the intestine, was purified from wound fluid and shown to possess syndecan-1 and syndecan-4 inductive activity specifically in mesenchymal cells. This is a newly recognized function that defines peptide containing syndecan-inducing activity, and that are known as synducins. Therefore a molecule with both antimicrobial and synducin activities is deposited in wounds where it can simultaneously reduce infection and influence the action of growth factors, matrix components, and other cellular effectors involved in wound repair. Synducins, including PR-39, and derivatives thereof, is therefore useful in the modulation of wound healing, as well as other disorders involving mesenchymal cells and cell surface molecular interaction, including metastatic disease, angiogenesis, restenosis, stasis or decubitis ulcers, and prevention of keloids.

Abstract: A drug delivery system including a plurality of microsphere particles containing an active drug and including a material associated with each particle which material has the property of increasing the bioavailability of the active drug.

Abstract: Disclosed is a method for identifying possible binding sites for RNA binding proteins in nucleic acid sequences, and confirming the identity of such prospective binding sites by detection of interaction between the prospective binding site and RNA binding proteins. Also disclosed are specific binding sites of RNA binding proteins which have been identified using this method.

Abstract: Immunodeficient animals are generated by introducing a mutation in RAG-1 into the germline of the animals via gene targeting in embryonic stem cells. The production of mutant RAG-1 deficient mice is detailed. RAG-1 deficient mice have no mature B and T lymphocytes. The arrest of B and T cell differentiation occurs at an early stage and correlates with the inability to perform V(D)J recombination. To date, these mice do not have mature B and T lymphocytes, nor do they express immunoglobulin or T cell receptors. The same strategy can be applied to the generation of other RAG-1 deficient animals, such as rabbits, rats, and pigs, using known techniques. These animals are all useful for the same general purposes as the scid mice, for example, cultivation of human lymphocytes for expression of human immunoglobulin.

Abstract: Water soluble macromers are modified by addition of free radical polymerizable groups, such as those containing a carbon-carbon double or triple bond, which can be polymerized under mild conditions to encapsulate tissues, cells, or biologically active materials. The polymeric materials are particularly useful as tissue adhesives, coatings for tissue lumens including blood vessels, coatings for cells such as islets of Langerhans, coatings, plugs, supports or substrates for contact with biological materials such as the body, and as drug delivery devices for biologically active molecules.

Abstract: It has been discovered that improved yields of engineered tissue following implantation, and engineered tissue having enhanced mechanical strength and flexibility or pliability, can be obtained by implantation, preferably subcutaneously, of a fibrous polymeric matrix for a period of time sufficient to obtain ingrowth of fibrous tissue and/or blood vessels, which is the removed for subsequent implantation at the site where the implant is desired. The matrix is optionally seeded prior to the first implantation, after ingrowth of the fibrous tissue, or at the time of reimplantation. The time required for fibrous ingrowth typically ranges from days to weeks. The method is particularly useful in making valves and tubular structures, especially heart valves and blood vessels.

Abstract: Aerodynamically light particles incorporating a surfactant on the surface thereof for drug delivery to the pulmonary system, and methods for their synthesis and administration are provided. In a preferred embodiment, the aerodynamically light particles are made of a biodegradable material and have a tap density less than 0.4 g/cm.sup.3 and a mass mean diameter between 5 .mu.m and 30 .mu.m. The particles may be formed of biodegradable materials such as biodegradable polymers. For example, the particles may be formed of poly(lactic acid) or poly(glycolic acid) or copolymers thereof. Alternatively, the particles may be formed solely of the drug or diagnostic agent and a surfactant. Surfactants can be incorporated on the particle surface for example by coating the particle after particle formation, or by incorporating the surfactant in the material forming the particle prior to formation of the particle. Exemplary surfactants include phosphoglycerides such as L-.alpha.-phosphatidylcholine dipalmitoyl.

Abstract: Disclosed are compositions and a method for of amplifying nucleic acid sequences useful for detecting the presence of molecules of interest. The method is useful for detecting specific nucleic acids in a sample with high specificity and sensitivity. The method also has an inherently low level of background signal. A preferred form of the method consists of a DNA ligation operation, an amplification operation, and a detection operation. The DNA ligation operation circularizes a specially designed nucleic acid probe molecule. This operation is dependent on hybridization of the probe to a target sequence and forms circular probe molecules in proportion to the amount of target sequence present in a sample. The amplification operation is rolling circle replication of the circularized probe. A single round of amplification using rolling circle replication results in a large amplification of the circularized probe sequences.

Abstract: It has been discovered that the incorporation of fluorinated gases, especially a perfluorocarbon such as octafluoropropane, into synthetic polymeric microparticles, significantly enhances echogenicity as compared with microparticles having air incorporated therein. The microencapsulated perfluorocarbon is manufactured with a diameter suitable for the targeted tissue to be imaged, for example, for intravenous or oral administration. In one embodiment, bioadhesive microparticles are formed for enhanced imaging of mucosal surfaces.

Abstract: Human protein C and activated protein C were shown to bind to endothelium specifically, selectively and saturably (Kd=30 nM, 7000 sites per cell) in a Ca.sup.2+ dependent fashion. Expression cloning revealed a 1.3 kb CDNA that coded for a novel type I transmembrane glycoprotein capable of binding protein C. This protein appears to be a member of the CD1/MHC superfamily. Like thrombomodulin, the receptor involved in protein C activation, the endothelial cell protein C receptor (EPCR) function and message are both down regulated by exposure of endothelium to TNF. Identification of EPCR as a member of the CD1/MHC superfamily provides insights into the role of protein C in regulating the inflammatory response, and determination of methods for pharmaceutical use in manipulating the inflammatory response.

Abstract: Described herein is a multi-functional polymeric material for use in inhibiting adhesion and immune recognition between cells and cells, cells and tissues, and tissues and tissues. One component of the polymeric material adsorbs well to cells or tissue, and the other component of the polymeric material does not adsorb well to tissues. A water-soluble polymer that does not bear charge (polynonion) is used as the non-binding component, and a water soluble polymer that is positively charged at physiological pH (polycation) is used as the tissue binding component. When the bi-functional polymeric material contacts a tissue, the tissue-binding component binds and thus immobilizes the attached non-binding component, which will then extend generally away from the tissue surface and sterically block the attachment of other tissues.