Abstract: This invention relates to the prognosis of outcome of infection with the human immunodeficiency virus (HIV). In particular, the present invention concerns monitoring individuals who are at risk for developing acquired immunodeficiency syndrome (AIDS), and individuals who are undergoing therapy for AIDS. The method for estimating the risk of the onset of a clinical event associated with infection with HIV broadly comprises evaluating the rate of HIV replication in peripheral blood cells from an individual suspected of suffering from HIV infection. More particularly, the method comprises determining the level of expression of HIV messenger RNA (mRNA) in peripheral blood cells of an asymptomatic individual. High level expression of HIV mRNA indicates a high likelihood of onset of symptoms of AIDS, and low level expression or determination of no detectable expression indicates a low likelihood of onset of symptoms of AIDS.

Abstract: The present invention relates to compositions and methods for preventing pneumococcal infection. In particular, this invention relates to the identification of the minimum receptor targets of pneumococcal adherence to pulmonary and vascular endothelium, and to compositions and methods for preventing such adherence. In particular, the invention relates to the ability of one or more carbohydrate entities having the following motif or motifs: a disaccharide N-acetyl-D-galactosamine .beta.1-3Gal motif, a disaccharide N-acetyl-D-galactosamine .beta.1-4Gal motif, and an N-acetyl-D-glucosamine motif, effective to induce elution of adherent S. pneumoniae from host cells. In particular, a composition containing all three motifs can elute about 100% of pneumococcal bacteria from lung epithelial cells, and from venous endothelial cells. In a particular embodiment, a pharmaceutical composition of the invention can be used to treat pneumococcal infections in which the host cells are lung epithelial cells.

Abstract: Glucagon analogs characterized principally by substitution of amino acid residues at positions 9, 11, 16, and 21 with or without a histidine residue at the amino terminus are useful adjuncts to insulin therapy.

Abstract: The present invention provides purified polypeptides useful as antimicrobial agents. These polypeptides comprise human polymorphonuclear leukocyte polypeptides having molecular weights of about 25,000 daltons, 29,000 daltons and 54,000 daltons. These polypeptides have respiratory burst-independent, antibacterial activity at a pH from about 5.0 to about 8.0, at calcium ion concentrations up to about 10 mM, and at sodium chloride concentrations up to about 0.3M.

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: Improved techniques are provided for DNA sequencing, and particularly for sequencing of the entire human genome. Different base-specific reactions are utilized to use different sets of DNA fragments from a piece of DNA of unknown sequence. Each of the different sets of DNA fragments has a common origin and terminates at a particular base along the unknown sequence. The molecular weight of the DNA fragments in each of the different sets is detected by a matrix assisted laser absorption mass spectrometer to determine the sequence of the different bases in the DNA. The methods and apparatus of the present invention provide a relatively simple and low cost technique which may be automated to sequence thousands of gene bases per hour, and eliminates the tedious and time consuming gel electrophoresis separation technique conventionally used to determine the masses of DNA fragments.

Abstract: A reagent, method and container for the isolation of cellular components such as ribonucleic acid (RNA) from cells in a liquid solution. The container includes a cover assembly and a holder which is normally closed by the cover assembly and contains an RNA extractant solvent, micron-sized particles and at least one larger particle suitably of millimeter size. The container contains the reagent, which is an extractant solvent which contains phenol and guanidinium thiocyanate or guanidinium chloride and has a pH of about 4. The container also includes a friable sealing layer which separates the extractant solvent from the liquid medium containing the cells until the container is reciprocally shaken. The method includes the reciprocal shaking of the container, wherein the larger particle breaks the friable layer to permit mixing of the liquid medium with the extractant solvent resulting in the breaking of the cell walls by the micron-size beads and the release of the RNA.

Abstract: The circulating advanced glycosylation endproducts Hb-AGE, serum AGE-peptides and urinary AGE-peptides are disclosed as long term markers of diseases and dysfunctions having as a characteristic the presence of a measurable difference in AGE concentration. Diagnostic and therapeutic protocols taking advantage of the characteristics of these AGEs are disclosed. Antibodies which recognize and bind to in vivo-derived advanced glycosylation endproducts are also disclosed. Methods of using these antibodies as well as pharmaceutical compositions are also disclosed, along with numerous diagnostic applications, including methods for the measurement of the presence and amount of advanced glycosylation endproducts in both plants and animals, including humans, as well as in cultivated and systhesized protein material for therapeutic use.

Abstract: The present invention relates to the role of dendritic cells in facilitating productive human immunodeficiency virus (HIV) infection. Experimentally, productive infection with HIV-1 requires that virus be administered to T cells that are activated by mitogens. This application describes a productive milieu for HIV-1 infection within the confines of normal epithelial tissue that does not require standard stimuli. The milieu consists of dendritic cells and T cells that emigrate from skin and produce distinctive stable, nonproliferating conjugates. These conjugates, upon exposure to HIV-1, begin to release high levels of virus progeny. Numerous infected syncytia, comprised of both dendritic cells and T cells, rapidly develop. A method is disclosed for the identification of agents capable of inhibiting HIV transmission and chronic infection of dendritic cells and T lymphocytes found in epithelial tissues.

Abstract: The circulating advanced glycosylation endproducts Hb-AGE, serum AGE-peptides and urinary AGE-peptides are disclosed as long term markers of diseases and dysfunctions having as a characteristic the presence of a measurable difference in AGE concentration. Diagnostic and therapeutic protocols taking advantage of the characteristics of these AGEs are disclosed. Antibodies which recognize and bind to in vivo-derived advanced glycosylation endproducts are also disclosed. Methods of using these antibodies as well as pharmaceutical compositions are also disclosed, along with numerous diagnostic applications, including methods for the measurement of the presence and amount of advanced glycosylation endproducts in both plants and animals, including humans, as well as in cultivated and systhesized protein material for therapeutic use.

Abstract: Process is described for the delivery and expression of hybrid surface proteins to the surface of bacteria. The transformed bacteria are useful as vaccines, for the delivery of other active peptides to animal hosts, as diagnostic reagents, and for other purposes.

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: The present invention relates to compounds, compositions and methods for inhibiting nonenzymatic cross-linking (protein aging). Accordingly, a composition is disclosed which comprises a di- or tri-aminoguanidine capable of inhibiting the formation of advanced glycosylation endproducts of target proteins. The method comprises contacting the target protein with the composition. Both industrial and therapeutic applications for the invention are envisioned, as food spoilage and animal protein aging can be treated.

Abstract: The present invention is directed to nucleic acids encoding vespid venom phospholipases, or fragments thereof, recombinant vectors comprising such nucleic acids, and host cells containing the recombinant vectors. The invention is further directed to expression of such nucleic acids to produce recombinant vespid venom phospholipases, or recombinant fragments, derivatives or analogs thereof. Such recombinant products are useful for diagnosis of allergy and for therapeutic treatment of allergy. In specific embodiments, the present invention provides nucleic acids encoding, and complete nucleotide and amino acids sequences for, vespid venom phospholipase A1, for example, Dolichovespula maculata phospholipase A.sub.1 and Vespula vulgaris phospholipase A1.

Abstract: HNF-4 (hepatocyte nuclear factor 4) is a protein enriched in liver extracts that binds to sites required for the transcription of the transthyretin (TTR) and apolipoprotein CIII (apoCIII) genes (Costa et al., 1989; Costa et al., 1990; Leff et al., 1989). We have purified HNF-4 protein (54 kD) and isolated a cDNA clone encoding the protein. HNF-4 is a member of the steroid hormone receptor superfamily with an unusual amino acid in the conserved "knuckle" of the first zinc finger (DGCKG). This and the fact that HNF-4 does not bind significantly to estrogen, thyroid hormone or glucocorticoid response elements indicate that HNF-4 may represent a new subfamily. HNF-4 binds to its recognition site as a dimer and activates transcription in a sequence-specific fashion in nonhepatic (HeLa) cells. HNF-4 mRNA is present in kidney and intestine as well as liver but is absent in other tissues.

Abstract: The present invention is directed to nucleic acids encoding vespid venom enzymes, or fragments thereof, recombinant vectors comprising such nucleic acids, and host cells containing the recombinant vectors. The invention is further directed to expression of such nucleic acids to produce recombinant vespid venom enzymes, or recombinant fragments, derivatives or analogs thereof. Such recombinant products are useful for diagnosis of allergy and for therapeutic treatment of allergy. In specific embodiments, the present invention provides nucleic acids encoding, and complete nucleotide and amino acids sequences for, vespid venom phospholipase, for example, Dolichovespula maculata phospholipase and Vespula vulgaris phospholipase, and vespid venom hyaluronidase, for example, Dolichovespula maculata hyaluronidase.

Abstract: This invention relates to the recognition and control of bacterial infections, particularly infections caused by Staphylococcus aureus (S. aureus). The present invention provides the staphylococcal accessory regulatory (sar) protein, and the gene encoding the sar protein (sar). The present invention also provides a diagnostic method for determining the pathogenicity of an S. aureus isolate using the sar gene.

Abstract: The present invention relates to receptors for advanced glycosylation endproducts derived from rat liver membranes, and that specifically comprise proteins determined to possess molecular masses of about 90 kD and 60 kD, respectively, as assessed by migration during SDS-PAGE. Partial N-terminal sequences have been determined and diagnostic and therapeutic agents, compositions and methods are proposed.

Abstract: Antibiotically and/or antimalarially active D-peptides of naturally occurring antibiotics such as cecropin A, B and D, melittin, and Magainin I and II and their addition, deletion and replacement analogs including homologous and heterologous analogs thereof.

Abstract: The present invention relates to a method and associated agents for the inhibition and treatment of protein aging in animals by stimulating the bodies of the animals to increase their recognition and affinity for advanced glycosylation end products. Specifically, the method contemplates the administration of certain agents such as advanced glycosylation endproducts, such endproducts as are bound to the carrier, monokines that stimulate phagocytic cells to increase their activity toward advanced glycosylation endproducts, and mixtures of these materials either alone, or in conjunction with other co-stimulatory agents. Numerous diagnostic and therapeutic applications are defined, and pharmaceutical compositions are also contemplated.