Abstract: Recombinant negative strand virus RNA templates which may be used to express heterologous gene products and/or to construct chimeric viruses are described. Influenza viral polymerase, which was prepared depleted of viral RNA, was used to copy small RNA templates prepared from plasmid-encoded sequences. Template constructions containing only the 3' end of genomic RNA were shown to be efficiently copied, indicative that the promoter lay solely within the 15 nucleotide 3' terminus. Sequences not specific for the influenza viral termini were not copied, and, surprisingly, RNAs containing termini identical to those from plus sense cRNA were copied at low levels. The specificity for recognition of the virus-sense promoter was further defined by site-specific mutagenesis. It was also found that increased levels of viral protein were required in order to catalyze both the cap-endonuclease primed and primer-free RNA synthesis from these model templates as well as from genomic lengths RNAs.

Abstract: A method for detecting point mutations or base substitutions in a nucleic acid polymer is especially useful for detecting such mutations in the highest melting domain (HMD) of a double-stranded nucleic acid polymer and is particularly suited for use with RNA. The method involves the steps of:(a) preparing a solution containing a double-stranded nucleic acid polymer comprising a duplex of a single-stranded nucleic acid polymer to be analyzed and a cThe invention described and claimed in this application was made with government support under Grant #DK-38381 awarded by the National Institutes of Health. The U.S. government has certain rights in the invention.

Abstract: Persons suffering from negative symptoms of schizophrenia can be successfy treated using a histamine H.sub.2 -antagonist which crosses the blood-brain barrier so as to interact with histamine-H.sub.2 receptors in the brain. A preferred H.sub.2 -antagonist is famotidine. The H.sub.2 -antagonist may be used alone in patients who are relatively free of positive symptoms or it may be used in combination with known neuroleptics. A pharmaceutical composition containing both an H.sub.2 -antagonist and a neuroleptic is part of the present invention.

Abstract: A method and devices for transcutaneous or transmucosal stimulation of the recurrent laryngeal nerve are provided. Recurrent laryngeal nerve stimulation is delivered by applying electric charge from an electrode in the form of a probe or an indwelling device to the intact neck skin at specific points along the tracheoesophageal groove or to mucosa within the esophagus, larynx, or trachea. In accordance with the present invention vocal cord excursion is related to frequency of the electrical stimulus.

Abstract: An apparatus for maintaining a patient's visual fixation and centration while marking the patient's cornea comprises a housing, a light source axially aligned and integral to the housing to maintain the patient's visual fixation and centration while the cornea is marked with the light source acting as a point source of light and enabling the patient to see a shadow image of the patient's pupil, and means for marking the cornea which are integral to the housing and positioned such that the light source and means for marking are axially aligned. A method for maintaining a patient's visual fixation and centration while marking the cornea employs the apparatus in such a manner that the patient looks directly at the center of the image emanating from the illuminated light source, which is a shadow image of the patient's pupil, and the means for marking are then employed to place a mark on the patient's cornea.

Abstract: A dynamic continuous flow enzyme reactor and method for carrying out and analyzing phospholipid-dependent enzyme reactions are provided. The enzyme reactor is a tubular member preferably a capillary tube, coated on its inner surface with a planar phospholipid bilayer membrane, optionally and preferably containing an enzyme or enzyme cofactor. The reactor is connectable at one end to a means for delivering fluid flow reagents to the reactor and is connectable at a second end to a means for analyzing an effluent exiting from the reactor. Preferably the enzyme cofactor in the phospholipid membrane is purified tissue factor and the fluid reagents are inactive blood clotting factors which become activated upon interaction with the phospholipid membrane through a tissue factor-mediated reaction.

Abstract: A method for the synthesis of sulfydryl-containing peptides which comprises forming a benzylthioether-linked solid support-bound thiol compound having at least one functional group for generating at least one peptide bond, sequentially coupling at least one protected amino acid or peptide to the compound until a peptide having desired amino acid sequence is obtained, and cleaving the benzylthioether linkage to release the peptide from the support with concomitant regenertion of the sulfydryl group in the peptides. The invention also encompasses compounds having the general formula ##STR1## wherein X is H, NH.sub.2, ##STR2## or acyl-NHY, said acyl being an amino acid or a peptide; Y is H, COOH, CONHNH.sub.2, ##STR3## the ester COOR.sup.1 in which R.sup.1 is selected from the group consisting of methyl, ethyl, phenyl, ortho-nitrophenyl and para-nitrophenyl, the amide CONH.sub.2, or the amide CONHR.sup.2 in which R.sup.2 is an amino acid or peptide; and providing that X and Y cannot both be H.

Abstract: A new technique is disclosed for assaying for the presence of invasive cancer. While based on leukocyte adherence inhibition, it is improved by using relatively long lived radio-labeled leukocytes, fractionation of the leukocytes to separately treat T-cells and monocytes and by providing for human plasma or serum in the incubation medium.

Abstract: A coaxial double lumen tube for use in hemoaccess which comprises an outer tube positioned over an inner tube, both tubes having an internal and external diameter and a wall thickness, the outer tube having an internal diameter which is at least 1 mm larger than the external diameter of the inner tube creating a space between the outer tube and the inner tube and a self-sealing, nonbiodegradeable, biocompatible polymer adhesive which evenly fills the space between the outer tube and the inner tube.

Abstract: This application discloses a method for assaying viruses in which viral particles or fragments are treated to expose M-protein, and the presence of M-protein is subsequently determined by an immunoassay technique. The M-protein of viruses is quite lipophilic and appears to bind preferentially to surfaces such as polystyrene. This permits the assay to be conducted on a convenient polystyrene or similar solid surface. Detection is preferably by means of an enzyme antibody conjugate.

Abstract: The present application discloses a short-term microbial assay useful in detecting chemical mutagens. A Bacillus subtilis which is infected with a strain of the temperate bacteriophage .phi.105 having a conditional lethal mutation is specifically illustrated. In the assay exogenous DNA from wild-type .phi.105 is reacted with a potential mutagen and then transfected into the B. subtilis carrying a mutated .phi.105 DNA. After plating, an increase in the frequency of clear plaques signifies that the test compound is mutagenic.The present invention provides a short-term mutagenicity test which detects frameshift as well as base substitution mutations induced by chemicals.

Abstract: A new technique is disclosed for assaying for the presence of invasive cancer. While based on leukocyte adherence inhibition, it is improved by using relatively long lived radio-labeled leukocytes, fractionation of the leukocytes to separately treat T-cells and monocytes and by providing for human plasma or serum in the incubation medium.

Abstract: An influenza vaccine is disclosed which comprises, as an active ingredient, neuraminidase antigen which has been isolated from an antigenically functional virus and has substantial cross-reactivity with the influenza virus against which the vaccine is to be effective. The neuraminidase antigen can be derived from a virus antigenically representative of the contemporary or prevalent influenza virus subtype of interest, e.g., H3N2, the Hong Kong variant of influenza.

Abstract: An influenza vaccine is disclosed which comprises, as an active ingredient, a recombinant, antigenically hydridized virus which has a hemagglutinin antigen that has substantially no cross-reactivity with those influenza viruses against which the vaccine is to be effective and a neuraminidase antigen which has substantial cross-reactivity with the influenza viruses against which the vaccine is to be effective. The neuraminidase can be derived from a virus antigenically representative of the contemporary or prevalent influenza virus of interest, e.g., H3N3, the Hong Kong variant of influenza, while the hemagglutinin antigen, in a preferred embodiment of the invention, is obtained from A-1/equine virus or from other influenza viruses of other antigenic subtypes, such as HON1 or H1N1.