Abstract: Human antibodies, preferably recombinant human antibodies, that specifically bind to human tumor necrosis factor &agr;(hTNF&agr;) are disclosed. These antibodies have high affinity for hTNF&agr; (e.g., Kd=10−8 M or less), a slow off rate for hTNF&agr; dissociation (e.g., Koff=10−3sec−1 or less) and neutralize hTNF&agr; activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. The antibodies, or antibody portions, of the invention are useful for detecting hTNF&agr; and for inhibiting hTNF&agr; activity, e.g., in a human subject suffering from a disorder in which hTNF&agr; activity is detrimental. Nucleic acids, vectors and host cells for expressing the recombinant human antibodies of the invention, and methods of synthesizing the recombinant human antibodies, are also encompassed by the invention.

Abstract: An iterative and regenerative method for sequencing DNA is described. This method sequences DNA in discrete intervals starting at one end of a double stranded DNA segment. This method overcomes problems inherent in other sequencing methods, including the need for gel resolution of DNA fragments and the generation of artifacts caused by single-stranded DNA secondary structures. A particular advantage of this invention is that it can create offset collections of DNA segments and sequence the segments in parallel to provide continuous sequence information over long intervals. This method is also suitable for automation and multiplex automation to sequence large sets of segments.

Abstract: Transgenic animals carrying two transgenes, the first coding for a transactivator fusion protein comprising a tet repressor and a polypeptide which directly or indirectly activates in eucaryotic cells, and the second comprising a gene operably linked to a minimal promoter operably linked to at least one tet operator sequence, are disclosed. Isolated DNA molecules (e.g., targeting vectors) for integrating a polynucleotide sequence encoding a transactivator of the invention at a predetermined location within a second target DNA molecule by homologous recombination are also disclosed. Transgenic animals having the DNA molecules of the invention integrated at a predetermined location in a chromosome by homologous recombination are also encompassed by the invention. Methods to regulate the expression of a tet operator linked-gene of interest by administering tetracycline or a tetracycline analogue to an animal of the invention are also disclosed.

Abstract: Methods for the early detection of HIV infection by detecting a change in signal transduction mediator activity, particularly, an enzyme mediator, more particularly a member of the src protein tyrosine kinase family. The methods are applicable to HIV detection with serum, plasma, blood cell lysates, urine and saliva media. The methods provide a very early, reliable, specific and sensitive test of seronegative HIV infection that is affordable and practical on a large scale.

Abstract: Transgenic animals carrying a transgene comprising a nucleic acid molecule encoding protein useful for regulating the expression of genes in eukaryotic cells and organisms in a highly controlled manner are disclosed. In the regulatory system of the invention, transcription of a tet operator-linked nucleotide sequence is stimulated by a transcriptional activator fusion protein composed of two polypeptides, a first polypeptide which binds to tet operator sequences in the presence of tetracycline operatively linked to a second polypeptide activates transcription in eukaryotic cells. In a preferred embodiment, the transgene encoding the transcriptional activator fusion protein is integrated at a predetermined location within the chromosome of the transgenic animal.

Abstract: The present invention relates to the use of creatine compounds such as, for example, creatine, creatine phosphate or analogs of creatine, such as creatine-pyruvate, creatine-ascorbate, cyclocreatine, 3 guanidinopropionic acid, guanidinoacetate, homocyclocreatine, guanidino benzoates as energy generating systems and antioxidants for preservation of skin against adverse aging effects and damage secondary to insults such as harmful sun radiations, stress and fatigue. The creatine compounds which can be used in the present method include (1) creatine, creatine phosphate and analogs of these compounds which can act as substrates or substrate analogs for creatine kinase; (2) molecules that mimic the biological activity of creatine (3) molecules that modulate the creatine kinase system.

Abstract: Modified forms of human interleukin-1&bgr; converting enzyme (ICE) that display proteolytic activity and, furthermore, have increased stability compared to unmodified human ICE are disclosed. Nucleic acid molecules encoding a modified p10 subunit of ICE, and recombinant vectors and host cells incorporating such nucleic acid molecules, are also disclosed. A modified ICE protein of the invention can be used to cleave proteolytically ICE substrates and to identify modulators of ICE activity in screening assays. Moreover, due to its enhanced stability, the modified ICE of the invention is particularly suitable for use in the preparation of ICE crystals for X-ray crystallography.

Abstract: A nonhuman animal having somatic and germ cells in which at least one allele of an endogenous SLP-76 gene is functionally disrupted is provided. The animal may be heterozygous or, more preferably, homozygous for the SLP-76 gene disruption and is preferably a mouse. In homozygous animals, the percentage of peripheral T cells is substantially decreased compared to wildtype animals, whereas the percentage of B cells and macrophages in the periphery is substantially normal, indicating that SLP-76 disruption causes a profound block in T cell development. The animals of the invention can be used, for example, as controls to evaluate the efficacy of SLP-76 inhibitors and to identify disease conditions that can be treated with SLP-76 inhibitors. A transgenic nonhuman animal having a functionally disrupted endogenous SLP-76 gene but which has been reconstituted with an exogenous SLP-76 transgene (e.g., a human SLP-76 gene or a SLP-76 gene whose expression in targeted to a particular cell population) is also provided.

Abstract: An iterative and regenerative method for sequencing DNA is described. This method sequences DNA in discrete intervals starting at one end of a double stranded DNA segment. This method overcomes problems inherent in other sequencing methods, including the need for gel resolution of DNA fragments and the generation of artifacts caused by single-stranded DNA secondary structures. A particular advantage of this invention is that it can create offset collections of DNA segments and sequence the segments in parallel to provide continuous sequence information over long intervals. This method is also suitable for automation and multiplex automation to sequence large sets of segments.

Abstract: Embodiments of the present invention are directed to non-naturally occurring cells and methods for screening compositions and genes which interact with interleukin 1 beta and interleukin-1 beta converting enzyme (ICE) processing, methods and non-naturally occurring cells for making ICE, and agonists and inhibitors of ICE.

Abstract: The present invention relates to the use of aminoguanidine compounds for treating diseases of the nervous system. Aminoguanidine compounds can be used as therapeutically effective agents against a variety of diseases of the nervous system such as diabetic and toxic neuropathies, peripheral nervous system diseases, Alzheimer's disease, Parkinson's disease, stroke, Huntington's disease, amyotropic lateral sclerosis, motor neuron disease, traumatic nerve injury, multiple sclerosis, dysmyelination and demyelination disorders, and mitochondrial diseases.

Abstract: The present invention relates to the discovery of novel genes encoding Tub interactor (TI) polypeptides. Therapeutics, diagnostics and screening assays based on these molecules are also disclosed.

Abstract: Isolated nucleic acids encoding allergens of Canis familiaris, Can f I or Can f II, are disclosed. A cDNA encoding a peptide having a Can f I activity and a predicted molecular weight of about 19,200 daltons is also described. A cDNA encoding a peptide having Can f II activity and a predicted molecular weight of about 18,200 daltons is also disclosed. The nucleic acids can be used as probes to detect the presence of Can f I or Can f II nucleic acid in a sample or for the recombinant production of peptides having a Can f I or Can f II activity. Peptides having a Can f I or Can f II activity can be used in compositions suitable for pharmaceutical administration or methods of diagnosing sensitivity to dog dander.

Abstract: The invention pertains to methods for detecting the presence or absence of a mutation associated with hypertrophic cardiomyopathy (HC). The methods include providing DNA which encodes a sarcomeric thin filament protein (e.g., .alpha.-tropomyosin or cardiac troponin T) and detecting the presence or absence of a mutation in the amplified product which is associated with HC. DNA encoding an actin-associated protein, a myosin-associated protein, or a sarcomeric protein other than .beta. cardiac heavy chain can also be used in the methods of the present invention. The invention further pertains to methods for diagnosing familial HC (FHC) in a subject. These methods typically include obtaining a sample of DNA which encodes a sarcomeric thin filament protein from a subject being tested for FHC and diagnosing the subject for FHC by detecting the presence or absence of a mutation in the sarcomeric thin filament protein which causes FHC as an indication of the disease.

Abstract: Isolated nucleic acids encoding allergens of Canis familiaris, Can f I or Can f II, are disclosed. A cDNA encoding a peptide having a Can f I activity and a predicted molecular weight of about 19,200 daltons is also described. A cDNA encoding a peptide having Can f II activity and a predicted molecular weight of about 18,200 daltons is also disclosed. The nucleic acids can be used as probes to detect the presence of Can f I or Can f II nucleic acid in a sample or for the recombinant production of petides having a Can f I or Can f II activity. Peptides having a Can f I or Can f II activity can be used in compositions suitable for pharmaceutical administration or methods of diagnosing sensitivity to dog dander.

Abstract: A method is disclosed for determining the chromosomal identity of a sample of genomic DNA. The genomic DNA is amplified and labeled by polymerase chain reaction using primers substantially complementary to interspersed repetitive DNA sequences. The amplified and labeled genomic DNA fragments are then contacted with chromosomal DNA of known identity under conditions in which the chromosome-specific, but not the interspersed repetitive DNA sequences, of the amplified and labeled genomic DNA fragments are available for hybridization. Specific hybridization to chromosomal DNA of known identity determines the chromosomal identity of the sample of genomic DNA.

Abstract: Isolated nucleic acids encoding allergens of Canis familiaris, Can f I or Can f II, are disclosed. A cDNA encoding a peptide having a Can f I activity and a predicted molecular weight of about 19,200 daltons is also described. A cDNA encoding a peptide having Can f II activity and a predicted molecular weight of about 18,200 daltons is also disclosed. The nucleic acids can be used as probes to detect the presence of Can f I or Can f II nucleic acid in a sample or for the recombinant production of peptides having a Can f I or Can f II activity. Peptides having a Can f I or Can f II activity can be used in compositions suitable for pharmaceutical administration or methods of diagnosing sensitivity to dog dander.

Abstract: The present invention relates to the use of deprenyl compounds to rescue damaged nerve cells in a patient and to kits containing deprenyl compounds useful for rescuing damaged nerve cells in a patient.

Abstract: Devices and methods for measuring the weakness of body lumens, and in particular, urethral sphincters and similar valves, are disclosed. In one embodiment of the invention, a catheter with a hollow fluted distal end can be inserted into a lumen. The hollow fluted distal end of the catheter is then expanded into an enlarged configuration. The measurement of resistance to withdrawal of the catheter in the enlarged configuration provides an indication of weakness of the lumen. In one aspect of the invention, the catheter is inserted into a bladder via the urethral sphincter and the weakness of the urethral sphincter is measured. In another aspect of the invention, a device for measuring weakness of a body lumen, such as a urethral sphincter and similar valves, can consist of a catheter with a hollow fluted distal end having of an array of wings, and an expanding means for radially expanding the wings into an enlarged configuration.

Abstract: The present invention relates to the use of deprenyl or derivatives or analogues of deprenyl to rescue damaged nerve cells in an animal; to pharmaceutical compositions containing deprenyl adapted for such use; and, to methods for the treatment of disorders of the nervous system by rescuing damaged nerve cells.