Abstract: The isolation, cloning and characterization of a human gene related to but distinct from EGF receptor gene has been described. Nucleotide sequence of the gene and amino acid sequence of the polypeptide encoded by the gene have been determined. The use of the nucleic acid probes and antibodies having specific binding affinity with said polypeptide for diagnostic and therapeutic purposes have also been described.

Abstract: Although it can be farnesylated, the mutant lamin A protein expressed in Hutchison Gilford Progeria Syndrome (HGPS) cannot be defarnesylated because the characteristic mutation causes deletion of a cleavage site necessary for binding the protease ZMPSTE24 and effecting defarnesylation. The result is an aberrant farnesylated protein (called “progerin”) that alters normal lamin A function as a dominant negative, as well as assuming its own aberrant function through its association with the nuclear membrane. The retention of farnesylation, and potentially other abnormal properties of progerin and other abnormal lamin gene protein products, produces disease. Farnesyltransferase inhibitors (FTIs) (both direct effectors and indirect inhibitors) will inhibit the formation of progerin, cause a decrease in lamin A protein, and/or an increase prelamin A protein. Decreasing the amount of aberrant protein improves cellular effects caused by and progerin expression.

Abstract: Disclosed are compounds of Formula I wherein X, Y, R1-R7, T1, T2, Z, and p are as described herein; a pharmaceutical composition comprising a compound of Formula I and a carrier; a method of inhibiting growth of a cell, which method comprises administering in an amount effective to inhibit growth a compound of Formula I; a method of treating cancer in a mammal, which method comprises administering in an amount effective to treat cancer a compound of Formula I; a method of treating a viral, parasitic, or bacterial infection of a cell, which method comprises administering in an amount effective to treat a viral, parasitic, or bacterial infection a compound of Formula I; and a method of preparing a compound of Formula I as described herein.

Abstract: Image contributions produced by an untagged specimen magnetization component in magnetic resonance imaging are controlled by applying one or more radiofrequency (RF) pulses that invert at least a portion of the untagged specimen magnetization. In an example, a specimen is tagged with a spatially modulated magnetization that is used to produce an image signal that includes a contribution associated with the tagged magnetization and an untagged magnetization. The untagged magnetization is substantially along an axial direction defined by an applied axial magnetic field. The untagged magnetization increases in magnitude because of so-called T1 relaxation. A contribution to the image signal increases for a predetermined time or to a predetermined magnitude, and a 180-degree pulse is applied to invert at least a portion of the untagged magnetization. The untagged magnetization is then antiparallel with respect to the applied axial magnetic field.

Abstract: Chimeric human-bovine respiratory syncytial virus (RSV) are infectious and attenuated in humans and other mammals and useful in vaccine formulations for eliciting an anti-RSV immune response. Also provided are isolated polynucleotide molecules and vectors incorporating a chimeric RSV genome or antigenome which includes a partial or complete human or bovine RSV “background” genome or antigenome combined or integrated with one or more heterologous gene(s) or genome segment(s) of a different RSV strain. Chimeric human-bovine RSV of the invention include a partial or complete “background” RSV genome or antigenome derived from or patterned after a human or bovine RSV strain or subgroup virus combined with one or more heterologous gene(s) or genome segment(s) of a different RSV strain or subgroup virus to form the human-bovine chimeric RSV genome or antigenome.

Abstract: The present disclosure provides a cDNA, protein sequence, and genomic structure of the human cardiac isoform of myosin light chain kinase (cMLCK), and describes mutations in the cMLCK gene that are associated with cardiac dysfunction. Methods are provided for identifying individuals who can harbor mutations in the cMLCK gene, or carry alleles that can predisposed them to cardiac dysfunction. Disclosed also is a significant role for cMLCK in modulating cardiac contractility. The cMLCK protein is shown herein to reduce the amplitude of stretch activation and increase the tension production, a property of muscle which has heretofore had an unknown role in cardiac contraction. Moreover, the cMLCK protein is shown to be regionally distributed in the heart, thereby having differential effects on contractility and stretch activation. Methods herein are provided to exploit this effect of cMLCK, to treat individuals who have or are prone to cardiac dysfunction.

Abstract: This invention provides bioactive conjugates. The bioactive conjugates include: (1) a cell recognition moiety that binds to ?2 macroglobulin receptor ?2-MR and (2) a bioactive moiety which: (a) has a biological activity, (b) does not function solely as an immunogen to invoke an immune response and (c) does not have ADP ribosylating activity. The bioactive conjugates of this invention are useful in methods of transporting the bioactive moiety across a polar epithelial membrane. Thus, this invention provides methods for parenteral administration of proteins without injection.

Abstract: Disclosed are prodrugs of inactivators of O6-alkylguanine-DNA alkyltransferase (AGT). The prodrugs are cleavable by the ?-glucuronidase enzyme, which is either administered to the patient or produced by necrotic tumor cells. The prodrugs are represented by the formula A-B-C, wherein A is a glucuronosyl residue linked through its 1-oxygen to the phenyl ring of B; B is a benzyloxycarbonyl group, optionally ring-substituted with one or more electron withdrawing groups; and C is an inactivator of AGT, e.g., a substituted or unsubstituted O6-benzylguanine or O6-benzyl-2?-deoxyguanosine. Also disclosed are additional inactivators of AGT, pharmaceutical compositions comprising an inactivator or prodrug and a pharmaceutically acceptable carrier, and a method of use of the inactivator or prodrug in enhancing the chemotherapeutic treatment of tumor cells in a mammal, e.g., a human, with an antineoplastic alkylating agent that causes cytotoxic lesions at the O6-position of guanine.

Abstract: Disclosed are (N)-methanocarba adenine nucleosides of the formula: as highly potent A3 adenosine receptor agonists, pharmaceutical compositions comprising such nucleosides, and a method of use of these nucleosides, wherein R1-R6 are as defined in the specification. These nucleosides are contemplated for use in the treatment a number of diseases, for example, inflammation, cardiac ischemia, stroke, asthma, diabetes, and cardiac arrhythmias. The invention also provides compounds that are agonists of both A1 and A3 adenosine receptors for use in cardioprotection.

Abstract: Disclosed herein are isolated monoclonal human antibodies that specifically binds insulin-like growth factor II (IGF-II) with an equilibrium dissociation constant (Kd) of 1 nM or less, wherein the antibody bind IGF-I with an equilibrium dissociation constant (Kd) of 1 mM or greater. The antibodies inhibit phosphorylation of the insulin-like growth factor receptor. Nucleic acids encoding these antibodies, expression vectors including these nucleic acids, and isolated host cells that express the nucleic acids are also disclosed. The antibodies can be used to detect human IGF-II in a sample. Methods of diagnosing a tumor are disclosed herein that utilize these antibodies. Methods of treating a subject with a tumor are also disclosed.

Abstract: The present invention provides phenylalanine derivatives that inhibit SH2 domain binding with a phosphoprotein. These derivatives include compounds of the formula: W—Y-(AA)n-Z wherein n is 0 to 15; Y is a phenylalanyl radical having a phenyl ring, an amine end, and a carboxyl end, the phenyl ring having one or more substituents, e.g., hydroxyl, carboxyl, formyl, carboxyalkyl, carboxyalkyloxy, dicarboxyalkyl, dicarboxyalkyloxy, dicarboxyhaloalkyl, dicarboxyhaloalkyloxy, and phosphonoalkyl, or phosphonohaloalkyl; W is a moiety attached to the nitrogen of Y and is, e.g.

Abstract: The invention provides an isolated or purified T cell receptor (TCR) having antigenic specificity for a cancer antigen, e.g., a renal cell carcinoma antigen, wherein the TCR recognizes the cancer antigen in a major histocompatibility complex (MHC)-independent manner. Also provided are related polypeptides, proteins, nucleic acids, recombinant expression vectors, isolated host cells, populations of cells, antibodies, or antigen binding portions thereof, and pharmaceutical compositions. The invention further provides a method of detecting the presence of cancer in a host and a method of treating or preventing cancer in a host using the inventive TCRs or related materials.

Abstract: Recombinant human parainfluenza virus type 2 (HPIV2) viruses and related immunogenic compositions and methods are provided. The recombinant HPIV2 viruses, including HPIV2 chimeric and chimeric vector viruses, provided according to the invention are infectious and attenuated in permissive mammalian subjects, including humans, and are useful in immunogenic compositions for eliciting an immune responses against one or more PIVs, against one or more non-PIV pathogens, or against a PIV and a non-PIV pathogen. Also provided are isolated polynucleotide molecules and vectors incorporating a recombinant HPIV2 genome or antigenome.

Abstract: Disclosed are compounds of the formula (I) wherein R is C1-C30 alkyl, which may be optionally further substituted with one or more of C5-C8 cycloalkyl groups, or a C5-C12 cycloalkyl, which may be optionally substituted with one or more C1-C30 alkyl groups, R? is hydrogen or lower alkyl, R? is a C1-C30 alkyl or halo, and the bond between C14 and C15 can be a single bond or double bond. Also disclosed are pharmaceutical compositions comprising such compounds and methods of use thereof. These compounds can find use in treating a number of diseases or conditions such as hypogonadism, osteoporosis, and anemia, in providing hormonal therapy and contraception, as an anabolic agent, and in suppressing the release of hormones such as the luteinizing hormone.

Abstract: A method for preserving information about cytosine methylation status in amplified nucleic acid molecules is disclosed. The method includes contacting a sample that contains nucleic acid molecules, such as nucleic acid molecules having or suspected of having methylated cytosines, with a modifying agent that converts the unmethylated cytosines to produce converted nucleic acid molecules. The converted nucleic acid molecule retains information about cytosine methylation. The method further involves contacting the sample with a DNA polymerase to amplify the converted nucleic acid molecules by multiple strand displacement amplification. The sample is not contacted with a nucleic acid ligase or an RNA polymerase. Also disclosed are methods for detecting cytosine methylation in a sample. Such methods include detecting the presence of the signature of cytosine methylation in a bisulfite treated DNA sample that has been amplified by multiple strand displacement.

Abstract: Chimeric human-bovine respiratory syncytial virus (RSV) are infectious and attenuated in humans and other mammals and useful in immunogenic compositions for eliciting an anti-RSV immune response. Also provided are isolated polynucleotide molecules and vectors incorporating a chimeric RSV genome or antigenome which includes a partial or complete human or bovine RSV “background” genome or antigenome combined or integrated with one or more heterologous gene(s) or genome segment(s) of a different RSV strain. Chimeric human-bovine RSV of the invention include a partial or complete “background” RSV genome or antigenome derived from or patterned after a human or bovine RSV strain or subgroup virus combined with one or more heterologous gene(s) or genome segment(s) of a different RSV strain or subgroup virus to form the human-bovine chimeric RSV genome or antigenome.

Abstract: A new polypeptide is disclosed that is specifically detected in the cells of the prostate, termed Novel Gene Expressed in Prostate (NGEP). Polynucleotides encoding NGEP are also disclosed, as are vectors including these polynucleotides. Host cells transformed with these polynucleotides are also disclosed. Antibodies are disclosed that specfically bind NGEP. Methods are disclosed for using an NGEP polypeptide, an antibody that specifically binds NGEP, or a polynucleotide encoding NGEP. Assays are disclosed for the detection prostate cancer. Pharamaceutical compositions including an NGEP polypeptide, an antibody that specifically binds NGEP, or a polynucleotide encoding NGEP are also disclosed. These pharmaceutical compositions are of use in the treatment of prostate cancer.

Abstract: Novel analogues and derivatives of novobiocin are provided, including compounds having modifications to the amide side chain, coumarin ring, and sugar moieties. The compounds of the present invention are useful as heat shock protein 90 inhibitors, and may be used as anticancer and neuroprotective agents.

Abstract: Specific fragments of vasostatin are disclosed. These fragments are of use in methods of stimulating the proliferation or survival of a hematopoietic cell exposed to a chemotherapeutic agent or irradiation. Methods of stimulating the proliferation or survival of a hematopoietic cell using these fragments are also disclosed. In one embodiment, methods are disclosed for stimulating the growth or survival of a hematopoietic stem cell with a fragment of vasostatin, in the presence of a growth factor.

Abstract: The present invention provides a nucleic acid sequence encoding a melanoma antigen recognized by T lymphocytes, designated MART-1. This invention further relates to bioassays using the nucleic acid sequence, protein or antibodies of this invention to diagnose, assess or prognoses a mammal afflicted with melanoma or metastata melanoma. This invention also provides immunogenic peptides derived from the MART-1 melanoma antigen and a second melanoma antigen designated gp100. This invention further provides immunogenic peptides derived from the MART-1 melanoma antigen or gp100 antigen which have been modified to enhance their immunogenicity. The proteins and peptides provided can serve as an immunogen or vaccine to prevent or treat melanoma.