Abstract: The present invention is directed to the identification of mutant strains of methicillin resistant bacteria, in particular methicillin resistant Staphylococcus aureus, to identify the characteristics of such bacteria and develop drugs that can reverse, inhibit, or reduce bacterial resistance to beta lactam antibiotics, e.g., methicillin. The invention particularly relates to identification of a novel mutant strain of methicillin resistant S. aureus that manifests a unique phenotype. Accordingly, the invention provides for methods of treatment and corresponding pharmaceutical compositions for treating bacterial, particularly staphylococcal, infections.

Abstract: The present invention relates, in general, to a method for the high level expression of the outer membrane protein meningococcal group B porin proteins and fusion proteins thereof. In particular, the present invention relates to a method of expressing the outer membrane protein meningococcal group B porin proteins in E. coli wherein the meningococcal group B porin proteins and fusion proteins thereof comprise more than 2% of the total protein expressed in E. coli. The invention also relates to a method of purification and refolding of the meningococcal group B porin proteins and fusion proteins thereof and to their use in vaccines.

Abstract: The present invention relates generally to the control of body weight of animals including mammals and humans, and more particularly to materials identified herein as modulators of body weight, and to diagnostic and therapeutic uses of such modulators. In its broadest aspect, the present invention relates to nucleotide sequences corresponding to the murine and human OB gene, and two isoforms thereof, and proteins expressed by such nucleotides or degenerate variations thereof, that demonstrate the ability co participate in the control of mammalian body weight and that have been postulated to play a critical role in the regulation of body weight and adiposity. The present invention further provides nucleic acid molecules for use as molecular probes or as primers for polymerase chain reaction (PCR) amplification. In further aspects, the present invention provides cloning vectors and mammalian expression vectors comprising the nucleic acid molecules of the invention.

Abstract: A method for producing proliferating cultures of dendritic cell precursors is provided. Also provided is a method for producing mature dendritic cells in culture from the proliferating dendritic cell precursors. The cultures of mature dendritic cells provide an effective means of producing novel T cell dependent antigens comprised of dendritic cell modified antigens or dendritic cells pulsed with antigen, including particulates, which antigen is processed and expressed on the antigen-activated dendritic cell. The novel antigens of the invention may be used as immunogens for vaccines or for the treatment of disease. These antigens may also be used to treat autoimmune diseases such as juvenile diabetes and multiple sclerosis.

Abstract: An inflammatory cytokine is disclosed which has been isolated from cells that have been incubated with a stimulator material. The inflammatory cytokine comprises a protein that is capable of binding to heparin, inducing localized inflammation characterized by polymorphonuclear cell infiltration when administered subcutaneously and inducing in vitro polymorphonuclear cell chemokinesis, while lacking the ability to suppress the activity of the anabolic enzyme lipoprotein lipase, cause the cytotoxicity of cachectin/TNF-sensitive cells, stimulate the blastogenesis of endotoxin-resistant C3H/HeJ thymocytes, or induce the production of cachectin/TNF by primary thioglycollate-elicited mouse macrophage cells. A particular inflammatory cytokine MIP-1 has been isolated and has been found to comprise a peptide doublet of similar molecular weights of about 8,000 daltons, and to show a pI of about 4.6. The doublet has been resolved into its component peptides, MIP-1.alpha. and MIP-1.beta.

Abstract: This invention is directed to a compound having the formula I. ##STR1## This invention is directed to a pharmaceutical composition comprising a compound which inhibits serotonin N-acetyltransferase having the formula I and a pharmaceutical acceptable carrier. The present invention relates to novel compounds and analogs which inhibit the serotonin N-acetyltransferase enzyme, and to processes for their preparation.

Abstract: The present invention is directed to the identification of mutant strains of methicillin resistant bacteria, in particular methicillin resistant Staphylococcus aureus, to identify the characteristics of such bacteria and develop drugs that can reverse, inhibit, or reduce bacterial resistance to beta lactam antibiotics, e.g., methicillin. The invention particularly relates to identification of a novel mutant strain of methicillin resistant S. aureus that manifests a unique phenotype, having a block in cell wall synthesis at or close to the branch point in hexose metabolism involved in the synthesis of cell wall components. Accordingly, the invention provides for methods of treatment and corresponding pharmaceutical compositions for treating bacterial, particularly staphylococcal, infections.

Abstract: Viruses of the family poxviridae such as vaccinia or fowlpox viruses are modified to contain a gene which expresses a protein corresponding to the conserved exposed region of the M6 protein. The modified products are useful as vaccines against streptococcal infection.

Abstract: Provided herein are novel nucleic acids which encode exported proteins of Gram positive bacteria, and the proteins encoded by such nucleic acids. Also provided are methods of producing such exported proteins, and vaccines for protecting an animal from infection with a gram positive bacterium, wherein the vaccines utilize the novel nucleic acids and proteins of the invention.

Abstract: Receptor recognition factors exist that recognizes the specific cell receptor to which a specific ligand has been bound, and that may thereby signal and/or initiate the binding of the transcription factor to the DNA site. The receptor recognition factor is in one instance, a part of a transcription factor, and also may interact with other transcription factors to cause them to activate and travel to the nucleus for DNA binding. The receptor recognition factor appears to be second-messenger-independent in its activity, as overt perturbations in second messenger concentrations are of no effect. The concept of the invention is illustrated by the results of studies conducted with interferon (IFN)-stimulated gene transcription, and particularly, the activation caused by both IFN.alpha. and IFN-.gamma..

Abstract: The present invention relates to novel imidazolium compounds and improved processes for the preparation of imidazolium cations with one or more imidazolium moieties optionally substituted with the same or different substituents, which are prepared from a reactant with at least one N--C--C--N group, by reacting with with an N-substituted or N,N-disubstituted thioformamide, formamide acetal or thioformamide acetal, in the presence of a halogenating agent. Examples of suitable halogenating agents include but are not limited to thionyl chloride, phosgene, and phosgene derivatives. Reactants containing more than one additional N--C--C--N group may also be used to prepare compounds with two or more imidazolium groups, by the procedures of the present invention. Certain compounds of the invention prepared from reactants with multiple N--C--C--N groups may have both unreacted N--C--C--N moieties and substituted imidazolium groups.

Abstract: Peptides which will inhibit the reaction between the RGD tripeptide of FHA and the integrin receptors of endothelial cells and their utility as therapeutic agents are described.

Abstract: The invention relates to an enzyme which cleaves surface proteins of gram-positive bacteria, to methods of detecting the enzyme, and methods of isolating the enzyme. In particular, the enzyme is isolated from a group A Streptococcus, and cleaves at the sequence LPXTGX (SEQ ID NO:1). A method for screening putative inhibitors of the enzyme which cleaves the anchor region of surface proteins from gram positive bacteria is also disclosed.

Abstract: The present invention provides a unique src-family kinase (SFK) that plays a key role in the transformation of early-stage embryonic cells to mesodermal cells. Furthermore, this src-family kinase is likely to be a proto-oncogene. The nucleic acid and amino acid sequences are disclosed.

Abstract: The present invention is directed to nucleic acids encoding glycosyltransferases, the proteins encoded thereby, and to methods for synthesizing oligosaccharides using the glycosyltransferases of the invention. In particular, the present application is directed to identification a glycosyltransferase locus of Neisseria gonorrhoeae containing five open reading frames for five different glycosyltransferases. The functionally active glycosyltransferases of the invention are characterized by catalyzing reactions such as adding Gal .beta.1.fwdarw.4 to GlcNAc or Glc; adding GalNAc or GlcNAc .beta.1.fwdarw.3 to Gal; and adding Gal .alpha.1.fwdarw.4 to Gal. The glycosyltransferases of the invention are particularly suited to the synthesis of the oligosaccharides Gal.beta.1.fwdarw.4GlcNAc.beta.1.fwdarw.3Gal.beta.1.fwdarw.4Glc (a mimic of lacto-N-neotetraose), GalNAc.beta.1.fwdarw.3Gal.beta.1.fwdarw.4GlcNAc.beta.1.fwdarw.3Gal.beta.l. fwdarw.4Glc.beta.1.fwdarw.4 (a mimic ganglioside), and Gal.alpha.1.fwdarw.4Gal.beta.1.

Abstract: The present invention relates to the identification of promoters of myelopoietic blood cell production. In particular, an agent has been discovered that enhances myelopoietic colony stimulating factor activity. The agent comprises cytokines that are also capable of binding to heparin, and inducing localized inflammation characterized by polymorphonuclear cell infiltration when administered subcutaneously. Particular agents comprise the inflammatory cytokines MIP-1 and MIP-2. Diagnostic and therapeutic utilities are proposed, and pharmaceutical compositions are likewise set forth.

Abstract: Methods are described for determining in individuals with or without a prior history of colorectal neoplasia whether the individual has had, has, or has a risk of developing colorectal neoplasia. The method involves an assessment of the extent of apoptosis, or programmed cell death, in a colorectal biopsy specimen. Any of numerous methods to measure the extent of apoptosis in the sample is contemplated. For example, normal-appearing mucosa from the distal colon and/or rectum may be obtained from individuals undergoing screening procedures for colorectal cancer. The tissue is subjected to a method that assesses apoptosis, for example, by the extent of broken DNA ends in the nuclei of the cells in the specimen. The extent of apoptosis is expressed as a numerical ratio and indicates the possibility that an individual patient has a premalignant or malignant lesion in his or her colon or the risk for the development of a colorectal neoplasm in the future.

Abstract: The present invention relates generally to the control of body weight of animals including mammals and humans, and more particularly to materials identified herein as modulators of weight, and to the diagnostic and therapeutic uses to which such modulators may be put. In its broadest aspect, the present invention relates to the elucidation and discovery of nucleotide sequences, and proteins putatively expressed by such nucleotides or degenerate variations thereof, that demonstrate the ability to participate in the control of mammalian body weight. The nucleotide sequences in object represent the genes corresponding to the murine and human ob gene, that have been postulated to play a critical role in the regulation of body weight and adiposity. Preliminary data, presented herein, suggests that the polypeptide product of the gene in question functions as a hormone.

Abstract: The present invention relates to compositions and methods for neutralizing lipopolysaccharide, and treatment of gram-negative sepsis based therein. Accordingly, the invention is directed to a composition of homogeneous particles comprising phospholipids and a lipid exchange protein, such as phospholipid transfer protein or LPS binding protein. The lipid exchange protein is characterized by being capable of facilitating an exchange protein of lipopolysaccharide into the particles. In a specific embodiment, exemplified herein, the lipid particles are high density lipoprotein particles comprising apolipoprotein A-I (apo A-I), a phospholipid, and cholesterol or a lipid bilayer binding derivative thereof. In a specific example, the phospholipid is phosphatidylcholine (PC). In a specific example, the ratio of phosphatidylcholine:cholesterol:apolipoprotein A-I is approximately 80:4:1.

Abstract: Peptides which will inhibit the reaction between the RGD tripeptide of FHA and the integrin receptors of endothelial cells and their utility as therapeutic agents are described.