Abstract: The present invention is directed to methods of detecting the presence of a bipolar mood disorder susceptibility locus in an individual, comprising analyzing a sample of DNA for the presence of a DNA polymorphism on the long arm of chromosome 18 between markers D18S469 and D18S554, wherein the DNA polymorphism is associated with a form of bipolar mood disorder. The invention for the first time provides strong evidence of a susceptibility gene for bipolar mood disorder that is located in the 18q22-q23 region of the long arm of chromosome 18. The disclosure describes the use of linkage analysis and genetic markers in this 18q22-q23 region to fine map the region and the use of genetic markers to genetically diagnose (genotype) bipolar mood disorder in individuals, to confirm phenotypic diagnoses of bipolar mood disorder, to determine appropriate treatments for patients with particular genotypic subtypes.

Abstract: A method to produce a cell expressing an antibody from a genomic sequence of the cell comprising a modified immunoglobulin locus using Cre-mediated site-specific recombination is disclosed. The method involves first transfecting an antibody-producing cell with a homology-targeting vector comprising a lox site and a targeting sequence homologous to a first DNA sequence adjacent to the region of the immunoglobulin loci of the genomic sequence which is to be converted to a modified region, so the first lox site is inserted into the genomic sequence via site-specific homologous recombination. Then the cell is transfected with a lox-targeting vector comprising a second lox site suitable for Cre-mediated recombination with the integrated lox site and a modifying sequence to convert the region of the immunoglobulin loci to the modified region.

Abstract: A disposable package, tape, and cassette are provided which makes it possible to hold and disperse therefrom liquid, flowable formulations including aqueous formulations (solutions or dispersions with particles less than 0.25 microns in diameter) of a pharmaceutically active drug. In one embodiment formulation is packaged in individual dosage unit containers which containers are preferably interconnected. The package is designed to be integrated into a cassette which can be loaded into a dispersing device capable of individually opening dosage unit containers and aerosolizing the contents through a porous membrane, into a mouth piece on the cassette, for delivery to a patient. In addition to and alongside of each porous membrane, the package may include one or more openings through which air is forced in order to aid in avoiding the accumulation of aerosolized particles.

Abstract: A method to produce a cell expressing an antibody from a genomic sequence of the cell comprising a modified immunoglobulin locus using Cre-mediated site-specific recombination is disclosed. The method involves first transfecting an antibody-producing cell with a homology-targeting vector comprising a lox site and a targeting sequence homologous to a first DNA sequence adjacent to the region of the immunoglobulin loci of the genomic sequence which is to be converted to a modified region, so the first lox site is inserted into the genomic sequence via site-specific homologous recombination. Then the cell is transfected with a lox-targeting vector comprising a second lox site suitable for Cre-mediated recombination with the integrated lox site and a modifying sequence to convert the region of the immunoglobulin loci to the modified region.

Abstract: Methods and devices are provided for detecting the presence of edema in a mammalian host. In the subject methods, at least one limbic extremity of the host, preferably a lower limbic extremity such as an ankle or foot, is introduced into a container of a displaceable medium to result in displacement of a portion of the medium. The displaced portion is measured and the measured value is then compared to a control value to identify any difference. The difference is then related to the presence of edema in the patient. The subject methods find use in the diagnosis and management of diseases characterized by the presence of edema as a physical manifestation, particularly congestive heart failure.

Abstract: The present invention provides a vector system that is useful for the generation of mutations in a recombination-based construction method. The invention further includes the incorporation of mutations generated by the method of the present invention into mouse embryonic stem cells and transgenic mice.

Abstract: The present invention features transgenic mice models for gene function, wherein the transgenic mice are characterized by having altered serotonin 5-HT6 receptor gene function. The transgenic mice may be either homozygous or heterozygous for a disruption in the endogenous 5-HT6 gene. Transgenic mice homozygous for a disruption in the endogenous 5-HT6 gene display a phenotype of increased anxiety behavior including diminished investigation of foreign objects and an elevation in stretched attend postures.

Abstract: The invention provides a method of suppressing ventricular muscle cell hypertrophy induced by an .alpha..sub.1 -adrenergic agonist or endothelin, by providing an effective amount of a retinoic acid compound.

Abstract: The need for the delivery of insulin by injection can be reduced or eliminated by delivering an aerosolized monomeric insulin formulation. Repeatability of dosing and more particularly the repeatability of the blood concentration versus time profile is improved relative to regular insulin. The blood concentration versus time profile is substantially unaffected by specific aspects of the patient's breathing maneuver at delivery. Further, the rate at which blood glucose is lowered is increased by the use of monomeric insulin. Particles of insulin and in particular monomeric insulin delivered to the surface of lung tissue will be absorbed into the circulatory system. The monomeric insulin may be a dry powder but is preferably in a liquid formulation delivered to the patient from a handheld, self-contained device which automatically releases an aerosolized burst of formulation.