Abstract: Compositions and methods for detecting the conversion to mucoidy in Pseudomonas aeruginosa are disclosed. Chronic respiratory infections with mucoid Pseudomonas aeruginosa are the leading cause of high mortality and morbidity in cystic fibrosis. The initially colonizing strains are nonmucoid but in the cystic fibrosis lung they invariably convert into the mucoid form causing further disease deterioration and poor prognosis. Mucoidy is a critical P. aeruginosa virulence factor in cystic fibrosis that has been associated with biofilm development and resistance to phagocytosis. The molecular basis of this conversion to mucoidy is also disclosed. The present invention provides for detecting the switch from nonmucoid to mucoid state as caused by either frameshift deletions and duplications or nonsense changes in the second gene of the cluster, mucA. Inactivation of mucA results in constitutive expression of genes, such as algD, dependent on algU for transcription.

Abstract: Disclosed are methods and compositions for the identification, characterization and inhibition of mammalian protein farnesyltransferases, enzymes involved in the farnesylation of various cellular proteins, including cancer related ras proteins such as p21.sup.ras. One protein farnesyltransferase which is disclosed herein exhibits a molecular weight of between about 70,000 and about 100,000 upon gel exclusion chromatography. Also disclosed are methods and compositions for the preparation of farnesyltransferase by recombinant means, following the molecular cloning and co-expression of its two subunits, for assay and purification of the enzyme, as well as procedures for using the purified enzyme in screening protocols for the identification of possible anticancer agents which inhibit the enzyme and thereby prevent expression of proteins such as p21.sup.ras.

Abstract: Disclosed are methods and compositions for producing heterologous disulfide bond containing polypeptides in bacterial cells. In preferred embodiments the methods involve co-expression of a prokaryotic disulfide isomerase, such as DsbC or DsbG and a gene encoding a recombinant eukaryotic polypeptide. Exemplary polypeptides disclosed include tissue plasminogen activator.

Abstract: Recombinant human immunodeficiency virus antigens capable of immunologically identifying the presence of early anti-HIV antibodies are stably expressed in a number of cell lines. These antigens have several clinically important applications as non-hazardous tools in the detection of human immunodeficiency virus exposure/infection, and in screening methods for HIV infection in idiopathic chronic lymphopenia (ICL). These techniques are improved over existing immunologically based and PCR based detection methods, as they provide for the detection of infection/exposure in samples determined to be negative by conventional forms of these types of assays that do not detect anti-HIV gp160 antibodies that react to conformational epitopes of HIV. The invention finds particular application in the detection of human immunodeficiency virus exposure/infection in infants.

Abstract: The invention pertains to novel genes which function in the regulation of DNA replication and/or entry of a cell into mitosis. The invention also pertains to novel proteins encoded by the genes described herein, antibodies which bind the encoded protein, and homologs of the novel genes which function in regulation of DNA replication and/or entry of a cell into mitosis and hybridize to the DNA sequence of the novel genes.

Abstract: This invention relates to an apparatus for inducing a pediatric patient breathing gas through a face mask to inhale a fluid pharmacological agent. The apparatus comprises a fluid conduit through which fluid pharmacological agent may be inhaled, and a sensory patient stimulator coupled to said conduit and accuatable by inspiratory or expiratory flow through said conduit.

Abstract: The invention relates to the field of radiation sensitizers and the use of texaphyrins for radiation sensitization and other conditions for which X-ray radiation has proven to be therapeutic.

Abstract: The retinoblastoma protein (Rb) is the product of the retinoblastoma gene and has been found to contain mutations in retinoblastoma tumor cells. Two nuclear proteins that bind to Rb, p48 and p46 have been isolated and the genes have been cloned. These proteins bind to Rb competitively with the SV40 T antigen. p48 is shown to suppress heat shock sensitive Ras mutations in yeast and is implicated as a modulator of the retinoblastoma suppressor function of Rb.

Abstract: Texaphyrins are provided for use as radiation sensitizers. Advantageous properties of texaphyrins for use as a radiation sensitizer include: i) a low redox potential which allows radiation-induced hydrated electrons to flow to texaphyrin rather than neutralizing hydroxyl radicals, allowing hydroxyl radicals to cause cellular damage, ii) a relatively stable texaphyrin radical that reacts readily to covalently modify neighboring molecules causing further cellular damage, iii) intrinsic biolocalization, and iv) indifference to the presence or absence of O.sub.2. These properties allow texaphyrins to be particularly effective for treating the hypoxic areas of solid neoplasms. Methods of treatment for an individual having a neoplasm or atheroma include the use of a texaphyrin as a radiation sensitizer and as an agent for photodynamic tumor therapy, or the use of a texaphyrin for internal and for external ionizing radiation. Novel texaphyrins are provided.

Abstract: The present invention relates to the use of tumor suppressor genes in combination with a DNA damaging agent or factor for use in killing cells, and in particular cancerous cells. A tumor suppressor gene, p53, was delivered via a recombinant adenovirus-mediated gene transfer both in vitro and in vivo, in combination with a chemotherapeutic agent. Treated cells underwent apoptosis with specific DNA fragmentation. Direct injection of the p53-adenovirus construct into tumors subcutaneously, followed by intraperitoneal administration of a DNA damaging agent, cisplatin, induced massive apoptotic destruction of the tumors. The invention also provides for the clinical application of a regimen combining gene replacement using replication-deficient wild-type p53 adenovirus and DNA-damaging drugs for treatment of human cancer.

Abstract: This invention concerns a novel optical micromanipulation tool, referred to as the optical stretcher, which may use a tunable laser to trap and deform cells between two counterpropogating beams generated by the laser. It is possible to detect the deformation of cancer cells.

Abstract: The invention discloses pH-controlling devices that comprise a biodegradable polymer and a pH-controlling substance, particularly an alkaline, acidic or buffering agents. By way of example, such alkaline agents include calcium carbonate and sodium bicarbonate. Methods of preparing such devices are also described. Methods for enhancing biocompatibility of an implantable device are also provided, as neutralizing alkaline materials are released at a rate that offsets changes in pH typically observed as polymers degrade to various acidic or alkaline by-products. By way of example, biodegradable polymers include PLA, PGA, polycaprolactone, copolymers thereof, or mixtures thereof. A new technique is disclosed to increase the surface porosity of porous implants which have a tendency to form relatively impermeable coverings. This technique entails the use of mechanical means to remove at least part of said covering, thus increasing the implant's surface porosity and permeability.

Abstract: Disclosed are compositions and methods of use that comprise engineered IgA antibodies that, when administered to a host are secreted across the epithelium into the mucosal barriers of the body providing external passive immunotherapy against agents such as viral, bacterial and eukaryotic pathogens. Also disclosed are mini antibodies comprising the minimal transcytosis domains.

Abstract: Hydrogels of polymerized and crosslinked macromers comprising hydrophilic oligomers having biodegradable monomeric or oligomeric extensions, which biodegradable extensions are terminated on free ends with end cap monomers or oligomers capable of polymerization and cross linking are described. The hydrophilic core itself may be degradable, thus combining the core and extension functions. Macromers are polymerized using free radical initiators under the influence of long wavelength ultraviolet light, visible light excitation or thermal energy. Biodegradation occurs at the linkages within the extension oligomers and results in fragments which are non-toxic and easily removed from the body. Preferred applications for the hydrogels include prevention of adhesion formation after surgical procedures, controlled release of drugs and other bioactive species, temporary protection or separation of tissue surfaces, adhering of sealing tissues together, and preventing the attachment of cells to tissue surfaces.

Abstract: This invention relates to a method for inhibiting bome resorption in a patient with periodotal disease by administering 3-[1-(4-chlorolbenzyl)-3-t-butyl-thio-t-isopropylindol-2-yl]-2,2dimethylpr opanoic acid.

Abstract: It was found that normal human stem cells produce a regulated non-processive telomerase activity, while cancer cells produce a processive telomerase activity. Nucleotide analogs, such as 7-deaza-2'-deoxyquanosine-5'-triphosphate (7-deaza-dGTP) were found to be substrates for processive telomerase and incorporated into telomeric sequence. The incorporation of this nucleotide subsequently affected the processivity of telomerase, converting processive telomerase to non-processive telomerase. The incorporation of this nucleotide analogs was also found to inhibit formation of G-quartets by telomeric sequence. Other methods for converting cancer processive telomerase to the more benign non-processive telomerase include partially cleaving the telomerase RNA.

Abstract: The present invention provides a planar light beam orientation device comprising a light source, a beam disperser, and a housing coupled to the light source and holding the beam disperser. The housing is configured to have a beam aperture configured to project a planar beam of light therefrom. The planar light beam orientation device of the present invention is capable of projecting a 360.degree. planar beam of light. The device is particularly useful in the orienting and reorienting of dental casts in a dental surveyor.

Abstract: The present invention relates generally to methods and compositions for targeting the vasculature of solid tumors using immunological- and growth factor-based reagents. In particular aspects, antibodies carrying diagnostic or therapeutic agents are targeted to the vasculature of solid tumor masses through recognition of tumor vasculature-associated antigens, such as, for example, through endoglin binding, or through the specific induction of endothelial cell surface antigens on vascular endothelial cells in solid tumors.

Abstract: Chimeric MHC Class I molecules having a recipient-type N-terminus, a donor-type alpha-1 helical region, and a recipient-type alpha-2 domain induce tolerance to donor grafts when administered to the recipient at time of transplantation.

Abstract: Methods for inhibiting the production of specific vasoconstrictive prostanoids, such as thromboxane and prostaglandin F.sub.2.alpha., through the addition of insulin-like growth factor, particularly IGF-I or IGF-II, to human placental cells are disclosed. IGF-I is demonstrated to avoid affecting material and placental production of prostaglandin E.sub.2, human chorionic gonadotropin, PGFM, and 6-keto-PGF1-alpha by placental cells. Improved methods for vasoregulation of vasoconstrictive diseases of pregnancy are also disclosed. Methods for treating intrauterine growth retardation and hypertension with IGF-I are described. Improved methods for inhibiting pre-term labor are provided. Methods for inducing labor with agents that specifically inhibit insulin-like growth factor are also disclosed. Such inhibitors of IGF-I include antibodies, antagonists of IGF-I, and metabolizing enzymes of IGF-I.