Abstract: Nucleic acids may be labeled by intercalating the alkylating intercalation moiety of a labeling reagent into a partially double-stranded nucleic acid to form a complex and activating the complex to cause covalent bonding between the reagent and the nucleic acid. Preferably, the labeled nucleic acid is a hybridization probe for detecting nucleic acid sequences capable of hybridizing with a hybridizing region of the nucleic acid. Also preferably the label moiety is non-radioactive. The labeling reagent is of the formula:[A--[B--Lwhere A is an alkylating intercalation moiety, B is a divalent organic moiety of the formula: ##STR1## where Y is O, NH or N--CHO, x is a number from 1 to 4, y is a number from 2 to 4, and L is a monovalent label moiety, wherein B is exclusive of any portion of the intercalation and label moieties.Preferably A is a 4-methylene-substituted psoralen moiety, and most preferably A is a 4'-methylene-substituted-4,5', 8-trimethylpsoralen moiety and L is biotin.

Abstract: An improved blind label is disclosed which includes a combination of open text and blinded text arrayed upon adhesive-backed label stock in an arrangement in which the label is divided into two sections joined by a tearable separation zone. In this improved label the first section is permanently affixable to the container to be labeled by its adhesive. The second section, carrying at least a portion of the blinded text, is strippably affixable to the container or to the first section by means of its adhesive backing. In certain embodiments, the blinding is accomplished by means of an opaque overcovering strippably adhered over the text with tamper-evident metallic layers being preferred overcoverings. An automatic labeling machine-compatible blind-label feedstock is also disclosed.

Abstract: At least two antigens in a sample may be detected using an immunometric dual sandwich assay containing an effective amount of at least one monoclonal antibody against each antigen, which antibodies are separately conjugated with the same or different signal moieties as labels, and an effective amount of at least one unlabeled monoclonal antibody against each antigen which unlabeled antibodies are immobilized on a single support. Preferably the antibodies are all products of different cell lines and the antigens are prostatic acid phosphatase and prostate antigen.

Abstract: The present invention is directed to a process for amplifying and detecting any target nucleic acid sequence contained in a nucleic acid or mixture thereof. The process comprises treating separate complementary strands of the nucleic acid with a molar excess of two oligonucleotide primers, extending the primers to form complementary primer extension products which act as templates for synthesizing the desired nucleic acid sequence, and detecting the sequence so amplified. The steps of the reaction may be carried out stepwise or simultaneously and can be repeated as often as desired.In addition, a specific nucleic acid sequence may be cloned into a vector by using primers to amplify the sequence, which contain restriction sites on their non-complementary ends, and a nucleic acid fragment may be prepared from an existing shorter fragment using the amplification process.

Abstract: In a method for detecting the presence or absence of a specific restriction site in a nucleic acid sequence an oligonucleotide probe complementary to one strand of the nucleic acid sequence spanning said restriction site is synthesized. The probe is labeled at the end nearer the restriction site. The nucleic acid is hybridized to the probe and a blocking oligomer may be added, if necessary, to prevent non-specific binding of the probe. Subsequent digestion with a restriction enzyme cleaves those oligomers that have hybridized to the nucleic acid and reformed the restriction site. The resulting cut and uncut labeled oligomers are separated and detected based on the type of probe label.The described method may be used to detect sickle cell anemia.

Abstract: The present invention is directed to a process for amplifying any desired specific nucleic acid sequence contained in a nucleic acid or mixture thereof. The process comprises treating separate complementary strands of the nucleic acid with a molar excess of two oligonucleotide primers, and extending the primers to form complementary primer extension products which act as templates for synthesizing the desired nucleic acid sequence. The steps of the reaction may be carried out stepwise or simultaneously and can be repeated as often as desired.

Abstract: Anti-Pseudomonas antibodies which bind to exotoxin A from P. aeruginosa are prepared from hybrid cell lines. The antibodies may be of any isotype. These antibodies may be used to treat infections caused by P. aeruginosa.

Abstract: An improved method for purifying TNF, especially recombinantly produced TNF in bacteria, is disclosed. The purification employs a hydrophobic support in a chromatographic column which is then developed, preferably by HPLC. Preliminary purifications using anion exchange resins are also helpful.

Abstract: A two-stage process for freeze-drying an aqueous solution of a dosage amount of cyclophosphamide to yield a hydrate of cyclophosphamide (referred to as "CPA" for brevity), comprises, in a first stage, freeze-drying a solution of CPA in combination with an excipient until the moisture content of the freeze-dried material is less than 2% by wt, based on the amount of anhydrous CPA present; and, in a second stage, rehydrating the freeze-dried material until the moisture content of the product is in the critical range of from about 2% to 7% by wt, based on the net wt of CPA product, it being essential for stability of the product that at least one sugar excipient be present. The process requires that a major amount by weight of the excipient(s) or all of it, be mannitol, optionally with an additional sugar and/or a carboxylic acid, and/or a buffer salt; and, the mannitol is present in an amount at least one-half (0.5 times) as mush as the CPA (anhyd) present.

Abstract: An apparatus and process for storing beads in a liquid medium and for draining and dispensing said beads essentially in the absence of said liquid medium is described. In one embodiment, the apparatus is designed so that the liquid medium in which the beads are stored can be captured in a separate compartment from the bead-containing compartment and the beads can be delivered without the liquid medium when the apparatus in inverted. This apparatus is designed so that the liquid medium will join with the beads for storage in the bead-containing compartment when the apparatus is upright. In another embodiment, the apparatus includes a bottle with a removable, threaded inner container which is used to drain the liquid medium from the beads prior to attachment to a separate bead dispenser.

Abstract: A 6-thioguanine-resistant subvariant of the EBV-transformed human lymphoblastoid B cell line WI-L2 is described. The subvariant line, designated LTR228, fuses efficiently with human cells. Human.times.human hybridomas derived from LTR228 that produce monoclonal antibodies against tetanus toxin and blood group A are exemplified.

Abstract: Monoclonal antibodies having conformation-dependent specificity for native dsDNA, as exemplified by the IgM antibody produced by murine hybridoma ATCC No HB 8329. These antibodies are used to detect DNA duplex formation in DNA hybridization tests.

Abstract: Nucleic acids may be labeled by intercalating the alkylating intercalation moiety of a labeling reagent into a partially double-stranded nucleic acid to form a complex and activating the complex to cause covalent bonding between the reagent and the nucleic acid. Preferably, the labeled nucleic acid is a hybridization probe for detecting nucleic acid sequences capable of hybridizing with a hybridizing region of the nucleic acid. Also preferably the label moiety is non-radioactive. The labeling reagent is of the formula:[A--[B--Lwhere A is an alkylating intercalation moiety, B is a divalent organic moiety of the formula: ##STR1## where Y is O, NH or N--CHO, x is a number from 1 to 4, y is a number from 2 to 4, and L is a monovalent label moiety, wherein B is exclusive of any portion of the intercalation and label moieties.Preferably A is a 4-methylene-substituted psoralen moiety, and most preferably A is a 4'-methylene-substituted-4,5',8-trimethylpsoralen moeity and L is biotin.

Abstract: HLA typing based on restriction length polymorphism is carried out by: digesting an individual's HLA DNA with a restriction endonuclease that produces a polymorphic digestion pattern with HLA DNA; subjecting the digest to genomic blotting using a labeled cDNA hybridization probe that is complementary to an HLA DNA sequence involved in the polymorphism; and comparing the resulting genomic blotting pattern with a standard. This technique may be adapted to make paternity or transplant or transfusion compatibility determinations or to make disease association correlations to diagnose diseases or predict susceptibility to diseases. Locus specific cDNA hybridization probes, particularly probes for genes of Class II loci (D and DR loci), for use in the typing procedure are described.

Abstract: A lightweight rear-wheel suspension for a bicycle which includes a triangulated main frame, a rear wheel support frame such as a rear fork rotatably supporting a rear wheel and mounted to the main frame so that it pivots about the foot crank rotational axis, providing upward and downward movement relative to the main frame, a spring-loaded hydraulic shock absorber for damping the relative movement of the rear wheel, said shock absorber having its outer housing incorporated as a rigid structural element of said triangulated main frame, its sliding piston assembly connected to said rear wheel support frame via a linkage system which converts the arcuate motion of said rear wheel support frame into linear motion in line with the linear motion of said sliding piston assembly, and incorporating a rider-controlled valve for hydraulically locking and unlocking said shock absorber, allowing the rear suspension to function both in a suspended mode and a rigid mode.

Abstract: A labeling reagent of the formula:[A][B]Lis prepared where A is an alkylating intercalation moiety, B is a divalent organic spacer arm moiety with a straight chain of at least two carbon atoms, and L is a monovalent label moiety capable of producing a detectable signal, e.g., a signal detectable by spectroscopic, photochemical, chemical, immunochemical or biochemical means. Preferably A is a 4'-methylene-substituted psoralen moiety, and most preferably A is a 4'-methylene-substituted 4,5',8-trimethylpsoralen moiety.This reagent may be used to label nucleic acids, preferably DNA, by intercalating the alkylating intercalation moiety of the reagent into an at least partially double-stranded nucleic acid to form a complex and activating the complex to cause covalent bonding between the reagent and the nucleic acid. Preferably, the labeled nucleic acid is a hybridization probe for detecting nucleic acid sequences capable of hybridizing with a hydridizing region of the nucleic acid.

Abstract: Reduced cysteine-containing proteins consisting of recombinant IFN-.beta., IL-2 or muteins thereof may be oxidized selectively so that the recombinant proteins have essentially the same disulfide bridging and biological activity as their native counterparts. The oxidized product is substantially free of unwanted side products and contains a minimal amount of intermolecular oligomers. The oxidation takes place in an aqueous medium containing a solubilizing agent at a pH of about 5.5 to 9, preferably at a pH of about 7. The reaction is initiated by addition of at least an effective amount of an oxidation promoter containing a Cu.sup.+2 cation such as CuCl.sub.2 or o-phenanthroline/Cu.sup.+2 complex in the presence of air.

Abstract: New multiclass hybrid interferon polypeptides, their corresponding encoding recombinant DNA molecules and transformed hosts which produce the new interferons are described. The amino acid sequences of these hybrids include at least two different subsequences, one of which has substantial homology with a portion of a first class of interferon (e.g., HuIFN-.alpha.) and the other which has substantial homology with a portion of a second class of interferon e.g., HuIFN-.beta.). Data indicates the interferon activity of .alpha.-.beta. hybrids may be substantially restricted to either cell growth regulatory activity or antiviral activity.

Abstract: An automatic liquid transfer system includes a horizontally translatable table and a pipette that is translatable both vertically and horizontally in a direction transverse to the axis of translation of the table. The table accommodates one or more titer trays having a multiplicity of receptacles to be filled, or holding liquid samples to be diluted, transferred, or aspirated, and a rack housing plural rows of disposable tips. Between each cycle in a liquid transfer process, a fresh tip is picked up by the pipette and used to transfer liquid in a sterile manner from a sample or diluent source to a well in the titer tray, or from one well to a different well anywhere on the one tray or to a receptacle in a different tray, where it is mixed with diluent. Thereafter, the tip is discharged back into the rack to maintain sterile conditions during the process and a new tip is installed.

Abstract: A composition of matter exhibiting a synergistic cytotoxic effect in combination therapy of certain breast cancer and myeloma cell lines is prepared by combining synergistically effective amounts of 5-fluorouracil and human recombinant beta-interferon, optionally together with a pharmaceutically effective diluent or carrier. Preferably the recombinant beta-interferon is a mutein in which the cysteine residue at position 17 of native beta-interferon is replaced by a serine residue.