Abstract: A polypeptide, called Tir (for translocated intimin receptor, which is secreted by attaching and effacing pathogens, such as the enteropathogenic (EPEC) and enterohemorrhagic (EHEC) E. coli. These bacterial pathogens inserts their own receptors into mammalian cell surfaces, to which the bacterial pathogen then adheres to trigger additional host signaling events and actin nucleation. Diagnosis of disease caused by pathogenic E. coli can be performed by the use of antibodies which bind to Tir to detect the protein or the use of nucleic acid probes for detection of nucleic acids encoding Tir polypeptide. Isolated nucleic acid sequences encoding Tir polypeptide, Tir peptides, a recombinant method for producing recombinant Tir, antibodies which bind to Tir, and a kit for the detection of Tir-producing E. coli are provided. A method of immunizing a host with Tir to induce a protective immune response to Tir or a second polypeptide of interest is also provided.

Abstract: This invention relates to derivatives of hemiasterlin or Geodiamolide G having anti-mitotic activities and useful in treating cancer. These derivatives are represented by general formula I, wherein Y, n, R1, R2, R3, R6, R7, R70, R71, R72, R74, and R75 are as defined in the specification.

Abstract: A method of identifying a polynucleotide or pattern of polynucleotides regulated by one or more sepsis or inflammatory inducing agents and inhibited by a peptide is described. A method of identifying a pattern of polynucleotide expression for inhibition of an inflammatory or septic response. The method includes contacting cells with LPS, LTA, CpG DNA and/or intact microbe or microbial components in the presence or absence of a cationic peptide; detecting a pattern of polynucleotide expression for the cells in the presence and absence of the peptide, wherein the pattern in the presence of the peptide represents inhibition of an inflammatory or septic response. Also included are compounds and agents identified by the methods of the invention. In another aspect, the invention provides methods and compounds for enhancing innate immunity in a subject.

Abstract: A method is provided for treating hormone-regulated tumors (for example, breast and prostatic tumors) in mammals, including humans, by administration of an antisense ODN which is complementary to a portion of the gene encoding IGFBP-5. Using the Shionogi tumor model in vitro and in vivo, the administration of such an ODN was shown to reduce proliferation of tumor cells, and also to delay the progression to androgen independence. Thus, treatment of prostate cancer in mammals, including humans, and delay of the progression of prostate tumors to androgen independence is accomplished by administering to the mammal a therapeutically effective amount of an antisense oligodeoxynucleotide which is complementary to a portion of the nucleic acid sequence encoding IGFBP-5 and which hybridizes with such a sequence to inhibit expression of IGFBP-5. Specific antisense ODN's which are suitable for use in the method are GACCACGCTGATCACCAT (Seq. ID. No.

Abstract: Multiple sclerosis and rheumatoid arthritis can be treated effectively using photodynamic therapy. In this protocol, a photoactive compound is administered, allowed to distribute in the effected subject, and the subject is then irradiated to activate the photoactive compound. Alternatively, the blood of a subject to be treated can be subjected to PDT extracorporeally. In the case of rheumatoid arthritis, localized treatment at the joints may also be employed.

Abstract: Disclosed herein are novel antimicrobial peptides with useful, improved, or superior properties such as antimicrobial activity, desirable levels of hemolytic activity, and therapeutic index against a broad range of microorganisms including gram-negative and gram-positive bacteria and other organisms having a cellular or structural component of a lipid bilayer membrane. Also provided are methods of making and using such peptides to control microbial growth and in pharmaceutical compositions for treatment or prevention of infections caused by such microorganisms. Certain peptides are disclosed utilizing a structure-based rational design relating to an antimicrobial peptide, V681, with single D-/L-amino acid substitutions or charged residue substitutions in or near the center of the peptide on the nonpolar or polar face. Also disclosed are peptides with one or more amino acids in the D configuration, including peptides with all amino acids in the D configuration.

Abstract: The present invention relates to methods, compositions and systems for producing hydrogen from water involving reacting metal particles with water in the presence of an effective amount of catalyst. In particular the invention pertains to methods, compositions and systems for producing hydrogen upon reaction of metal particles selected from the group consisting of aluminum (Al), magnesium (Mg), silicon (Si) and zinc (Zn) with water, in the presence of an effective amount of a catalyst, wherein the catalyst is a water-soluble inorganic salt.

Abstract: In accordance with various aspects of the invention, CXCR4 antagonists may be used to treat hematopoietic cells, such as progenitor or stem cells, to promote the rate of cellular multiplication, self-renewal, proliferation or expansion. CXCR4 antagonists may be used therapeutically to stimulate hematopoietic stem/progenitor cell multiplication/self-renewal.

Abstract: The invention provides a variety of therapeutic uses for CXCR4 antagonists. In various embodiments, CXCR4 antagonists may be used as therapeutically as follows, or to manufacture a medicament for such therapeutic treatments: reducing interferon gamma production by T-cells, treatment of an autoimmune disease, treatment multiple sclerosis, treatment of cancer, inhibition of angiogenesis. The invention provides corresponding methods of medical treatment, in which a therapeutic dose of a CXCR4 antagonist is administered in a pharmacologically acceptable formulation. Accordingly, the invention also provides therapeutic compositions comprising a CXCR4 antagonist and a pharmacologically acceptable excipient or carrier. The CXCR4 antagonists for use in the invention may be peptide compounds comprising a substantially purified peptide fragment, modified fragment, analogue or pharmacologically acceptable salt of SDF-1.

Abstract: Novel lipid-nucleic acid particulate complexes which are useful for in vitro or in vivo gene transfer are described. The particles can be formed using either detergent dialysis methods or methods which utilize organic solvents. Upon removal of a solubilizing component (i.e., detergent or an organic solvent) the lipid-nucleic acid complexes form particles wherein the nucleic acid is serum-stable and is protected from degradation. The particles thus formed have access to extravascular sites and target cell populations and are suitable for the therapeutic delivery of nucleic acids.

Abstract: Derivatives of hemiasterlin or Geodiamolide G having anti-mitotic activities and useful in treating cancer. These derivatives are represented by formula I wherein Y, n, R1, R2, R3, R7, R70, R71, R72, R74, and R75 are as defined in the specification.

Abstract: The present invention provides a method for detecting cancer in a patient. A sample from the patient is provided, and the level of oviduct-specific glycoprotein (OGP) in the sample is determined and compared to a control sample. Increased levels of OGP in the sample as compared to the control indicates that the patient has cancer. In one aspect, the cancer is a gynecological cancer, such as ovarian cancer. Kits for conducting the methods of the invention are also provided.

Abstract: An apparatus with means for controlling ion generation is discussed. The apparatus comprises a plurality of ion sources, at least one counter electrode mounted downstream for the ion sources and at least one ion controlling element mounted relative to at least one of the ion sources. Each ion controlling element is alternated between a first condition where the operation of at least one of the ion sources is enabled and a second condition where the operation of at least one of the ion sources is disabled. This concept may also be extended to an ion source apparatus having a single ion source with an ion lens mounted relative thereto. The present invention also provides a method for controlling the operation of the aforementioned apparatus. The invention further provides an apparatus and a method for the generation of ion pulses.

Abstract: A novel class of cationic peptides having antimicrobial activity is disclosed. These peptides can be encompassed by the formulas: X1X1PX2X3X2P(X2X2P)nX2X3(X5)0; (SEQ ID NO:23) X1X1PX2X3X4(X5)rPX2X3X3; (SEQ ID NO:24) X1X1X3(PW)uX3X2X5X2X2X5X2(X5)0; and (SEQ ID NO:25) X1X1X3X3X2P(X2X2P)nX2(X5)m; (SEQ ID NO:26) wherein: m is 1 to 5; n is 1 or 2; o is 2 to 5; r is 0 to 8; u is 0 or 1; X1 is Isoleucine, Leucine, Valine, Phenylalanine, Tyrosine, Tryptophan or Methionine; X2 represents Tryptophan or Phenylalanine X3 represents Arginine or Lysine; X4 represents Tryptophan or Lysine; and X5 represents Phenylalanine, Tryptophan, Arginine, Lysine, or Proline. The invention also provides a method of producing a cationic peptide variant having antimicrobial activity.

Abstract: In accordance with various aspects of the invention, CXCR4 agonists, including SDF-1 polypeptides and SDF-1 polypeptide homologues, may be used in reducing the rate of hematopoietic cell multiplication. Methods of the invention may comprise administration of an effective amount of an CXCR4 agonist to cells selected from the group consisting of hematopoietic stem cells and hematopoietic progenitor cells. Cells may be treated in vitro or in vivo in a patient. A therapeutically effective amount of the CXCR4 agonist may be administered to a patient in need of such treatment. Patients in need of such treatments may include, for example patients requiring bone marrow or peripheral blood stem cell transplantation.

Abstract: It has been determined that antisense therapy which reduces the expression of TRPM-2 provides therapeutic benefits in the treatment of cancer, particularly prostate and renal cell cancers. Addition of antisense TRPM-2 ODN to prostatic tumor cells in vivo is effective for delaying the onset of androgen independence, thus prostate cancer can be treated by initiating androgen-withdrawal to induce apoptotic cell death of prostatic tumor cells in an individual, and administering a composition effective to inhibit expression of TRPM-2 by the tumor cells. Combined use of antisense TRPM-2 and taxanes synergistically enhances cytotoxic chemosensitivity of androgen-independent prostate cancer and in human Renal cell cancer. Radiation sensitivity is also enhanced when cells expressing TRPM-2 are treated with antisense TRPM-2 ODN.

Abstract: This invention provides methods, nucleic acids, compounds, and compositions for expressing a product of interest in a cell that involve a secretable RNA Polymerase.

Abstract: The invention provides a variety of therapeutic uses for CXCR4 antagonists. In various embodiments, CXCR4 antagonists may be used as therapeutically as follows, or to manufacture a medicament for such therapeutic treatments: reducing interferon gamma production by T-cells, treatment of an autoimmune disease, treatment of multiple sclerosis, treatment of cancer, inhibition of angiogenesis. The invention provides corresponding methods of medical treatment, in which a therapeutic dose of a CXCR4 antagonist is administered in a pharmacologically acceptable formulation. Accordingly, the invention also provides therapeutic compositions comprising a CXCR4 antagonist and a pharmacologically acceptable excipient or carrier. The CXCR4 antagonists for use in the invention may be peptide compounds comprising a substantially purified peptide fragment, modified fragment, analogue or pharmacologically acceptable salt of SDF-1.

Abstract: Methods for the preparation of a lipid-nucleic acid composition are provided. According to the methods, a mixture of lipids containing a protonatable or deprotonatable lipid, for example an amino lipid and a lipid such as a PEG- or Polyamide oligomer-modified lipid is combined with a buffered aqueous solution of a charged therapeutic agent, for example polyanionic nucleic acids, to produce particles in which the therapeutic agent is encapsulated in a lipid vesicle. Surface charges on the lipid particles are at least partially neutralized to provide surface-neutralized lipid-encapsulated compositions of the therapeutic agents. The method permits the preparation of compositions with high ratios of therapeutic agent to lipid and with encapsulation efficiencies in excess of 50%.

Abstract: Methods and kits for detecting cancer and monitoring cancer progression are described. The method involves analyzing a sample containing nucleic acids or proteins from a patient for decreased expression of endoglycan and/or increased expression of podocalyxin.