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Compounds with planar triple ring systems such as acridine orange, 9-amino acridine, 9-amino-1,2,3, 4-tetrahydroacridine (tacrine), 6,9-diamino-2-ethoxyacridine lactate monohydrate (DE-acridine), 6-chloro-9-(3'-diethylamino-2'-hydroxypropylamino)-2-methoxyacridine 2 HCI (CDM-acridine), quinacrine, 6-chloro-9-(4'-diethylamino-1'-methylbutylamino) .2-methoxy. 1, 10-diazaanthracene (CDM 1, 10-diazaanthracene), thionine, azure A, methylene blue, and pyronine Y when applied to excised pea pods were potent inducers of phenylalanine ammonia lyase or of pisatin, or of both. Compounds with an array of structural variation around the planar three-ring system were tested for their ability to induce these responses in pea tissue. In general, dimethylamino, diethylamnino, or amino substitutions at position 2 and 6 or an amino (with or without an aliphatic side chain) substitution at position 9 of the three-ring system augmented induction potential. Methyl green, methylene blue, 2, 7-diaminofluorene, nile blue, neutral red, pyrogallol red, ethidium bromide, nogalamycin, quinine, chloroquine, spermine, 8-azaguanine, gliotoxin, chromomycin A3, actinomycin D, and mitomycin C were also potent inducers.The inhibition of phenylalanine ammonia lyase induction by the application of actinomycin D (300 micrograms per milliliter) or 6-methylpurine (1 milligram per milliliter) within 1 hour after inducer application indicated that newly synthesized RNA is necessary for induction. Phenylalanine ammonia lyase induction was also inhibited by cycloheximide (150 micrograms per milliliter).Various chemicals with the potential to intercalate into DNA molecules have been used extensively to study DNA structure and mutagenic, antiviral, antimitotic, anticarcinogenic, antimalarial activity (1,30,37,48 Methods. Experiments quantitating pisatin production and PAL activity utilized 1 g of fresh immature pea pods (1-2 cm long, harvested while still enclosed in the blossom). The general procedure, which involved splitting the pods and administering 1.5 ml of the aqueous solutions of the inducer compounds to the exposed pea endocarp, has been described in detail previously (41).Standardized methods for the isolation and quantitation of pisatin (41)

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Objective-To improve the understanding of the pathogenesis of rheumatoid arthritis (RA) by identifying novel, disease specific autoantibodies. Methods-Total protein preparations from synovial membranes were separated electrophoretically and immunoblotted. Sera from RA patients were screened for predominant immunoreactions by blotting. A 68 kDa antigen target of the most predominant reaction was detected and further characterised. Results-The dominant immunoreaction in most of the RA sera tested was with a 68 kDa antigen. The antigen is probably ubiquitously expressed. It has an isoelectric point of 5-1, is O-glycosylated, and is located in the endoplasmic reticulum, the cytoplasm, or both. Antibodies to the 68 kDa autoantigen were present in 64% of 167 RA patients tested, and could also be detected in seronegative RA patients, but were present in only 1% of 98 patients with other rheumatic diseases. They could not be detected in 55 healthy controls. Conclusions-Because of its high sensitivity (64%) and specificity (99%), the anti-68 kDa autoantibody not only provides another valuable parameter for diagnosis, but also represents an antibody that may be involved in the pathological mechanisms leading to RA. This hypothesis can be tested by investigating if 68 kDa specific T cells are present in RA patients.