Background Neutralization of tumor necrosis factor α (TNF-α) for three to six months reduces the symptoms and signs of rheumatoid arthritis. However, the capacity of this approach to effect a more sustained benefit and its effect on joint damage are not known. Methods We treated 428 patients who had active rheumatoid arthritis despite methotrexate therapy with placebo or infliximab, a chimeric monoclonal antibody against TNF-α, in intravenous doses of 3 or 10 mg per kilogram of body weight every 4 or 8 weeks in combination with oral methotrexate for 54 weeks. We assessed clinical responses with use of the criteria of the American College of Rheumatology, the quality of life with a health-status questionnaire, and the effect on joint damage radiographically. Results The combination of infliximab and methotrexate was well tolerated and resulted in a sustained reduction in the symptoms and signs of rheumatoid arthritis that was significantly greater than the reduction associated with methotrexate therapy alo...

Infliximab and methotrexate in the treatment of rheumatoid arthritis. Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group.

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Infliximab and methotrexate in the treatment of rheumatoid arthritis

Publisher Summary Autoantibodies to nuclear antigens (ANAs) have assumed an important place in the diagnostic armamentarium of the clinician because of distinct profiles of ANAs in different diseases. Profiles of ANAs have, therefore, been extremely useful in differential diagnosis, where the disease does not have classical or full-blown manifestations.. Immune complexes formed in the circulation or in situ mediate tissue injury by the activation of complement and other inflammatory mediators. Not only do these antibodies precipitate their respective antigens but also other proteins or nuclear RNAs that might be associated with them in special ways. The reasons for these special associations of protein antigens with specific sets of nuclear RNAs is unknown, but the possibility that there might be functional relationships in these complexed particles is not unreasonable. The key question that pervades the minds of many investigators in this field is the reason for the appearance of ANAs in certain individuals. It is highly improbable that the phenomenon is a random immune response to nuclear breakdown products, because the types of ANAs in different diseases are strikingly different. Some known environmental agents are drugs, such as hydralazine and procainamide, that together with lower levels of hepatic acetyltransferase enzyme predispose the host to the development of ANAs. Another agent may be the Epstein–Barr virus that is a ubiquitous environmental agent.

Autoantibodies to nuclear antigens (ANA): their immunobiology and medicine.

As the decade progresses this prediction is rapidly being realized, and microbial enzymes are becoming increasingly important in such diverse fields as medicine, brewing, and timber preservation. The genus Bacillus has played a major role in this development as evidenced by the distribution of the papers read at the Fifth International Fermentation Symposium, 1976 (64). Of 23 papers in the session devoted to "Microbial Enzymes of Industrial Interest" no less than ten were concerned with enzymes from bacilli. Reasons for the predominance of these bacteria in this area of study are several. First, they comprise a group of chemoorganotrophs that can be easily maintained and cultivated and yet are markedly heterogeneous in character. Psychrophiles, mesophiles, and thermophiles, in addition to alkalophilic, neutrophilic, and acidophilic species are well represented. Furthermore, virtually all 48 species of the genus listed in Bergey's Manual ofDeterminative Bacteriology (92) secrete a variety of soluble extracellular enzymes, which reflects the diversity of the parental habitats. Amylases that can liquefy starch under pressure at 11000 (194) and proteases that are stable and active at pH 12.0 (6) are extreme examples of enzyme adaption. This article will attempt to review the recent literature concerned with the characterization and properties of the exoenzymes synthesized by the bacilli and the control and mechanisms of their synthesis. It is restricted to this genus because the commercial importance of extracellular enzymes and academic interest in the process of sporulation have prompted a considerable amount of research into this general area. Nevertheless, in the final section I have attempted to equate our present knowledge of exoenzyme synthesis in procaryotes other than

Extracellular enzyme synthesis in the genus Bacillus.

Objectives: To evaluate further in a phase III, double blind trial the efficacy of infliximab in patients with active psoriatic arthritis (PsA), as observed in the smaller IMPACT trial. 

Methods: 200 patients with active PsA unresponsive to previous treatment were randomised to infusions of infliximab 5 mg/kg or placebo at weeks 0, 2, 6, 14, and 22. Patients with inadequate response entered early escape at week 16. The primary measure of clinical response was ACR20. Other measures included Psoriatic Arthritis Response Criteria (PsARC), Psoriasis Area and Severity Index (PASI), and dactylitis and enthesopathy assessments. 

Results: At week 14, 58% of patients receiving infliximab and 11% of those receiving placebo achieved an ACR20 response and 77% of infliximab patients and 27% of placebo patients achieved PsARC (both p<0.001). Among the 85% of patients with at least 3% body surface area psoriasis involvement at baseline, 53/83 (64%) patients receiving infliximab had at least 75% improvement in PASI compared with 2/87 (2%) patients receiving placebo at week 14 (p<0.001). These therapeutic effects were maintained through the last evaluation (week 24). Fewer infliximab patients than placebo patients had dactylitis at week 14 (18% v 30%; p = 0.025) and week 24 (12% v 34%; p<0.001). Fewer infliximab patients (22%) than placebo patients (34%) had active enthesopathy at week 14 (p = 0.016); corresponding figures at week 24 were 20% and 37% (p = 0.002). Infliximab was generally well tolerated, with a similar incidence of adverse events in each group. 

Conclusions: Infliximab 5 mg/kg through 24 weeks significantly improved active PsA, including dactylitis and enthesopathy, and associated psoriasis.

https://ard.bmj.com/content/annrheumdis/64/8/1150.full.pdf

Infliximab improves signs and symptoms of psoriatic arthritis: results of the IMPACT 2 trial

Antibody to DNA in human serums can be detected by the ammonium sulfate method. This sensitive and specific technique, which measures the primary interaction between DNA and antibody to DNA, is based on the observation that free DNA is soluble in 50-percent saturated ammonium sulfate whereas antibody-bound DNA is insoluble.

https://science.sciencemag.org/content/sci/161/3843/806.full.pdf

Deoxyribonucleic Acid Antibody: A Method to Detect Its Primary Interaction with Deoxyribonucleic Acid

Many of the viruses which infect Bacillus subtilis require glucosylated polyglycerol teichoic acid for adsorption. These mutants can be divided into three classes on the basis of enzymatic defects and growth on galactose-minimal medium. Transduction with phage PBS1 reveals that two of these, gtaA and gtaB, are linked to hisA1, whereas the gtaC locus is linked to argC. Analysis by deoxyribonucleic acid-mediated transformation indicates that these loci exist in a cluster between the hisA1 and argC4 loci. Anomalies in mapping in the group II region of the chromosome exist. The basis of these anomalies is discussed.

Chromosomal Location of Genes Regulating Resistance to Bacteriophage in Bacillus subtilis

Immediately after uptake of tritiated DNA into the bacterial cell, the label is located adjacent to the cell wall. Cell fractionation studies indicate that the newly acquired DNA is bound to the cytoplasmic membrane, not the cell wall.

Competence in Bacillus subtilis Transformation System

Dynamic interactions between cell wall polymers, extracellular proteases and autolytic enzymes.

The physiological and biochemical properties of a species of Bacillus previously identified as B. subtilis NRRL B-3275 (B-3275) were compared with those of seven strains of B. pumilus and five strains of B. subtilis. The biotin requirement of B-3275, its inability to hydrolyze starch, and its failure to reduce nitrate indicate that the organism is more closely related to the B. pumilus strains than to those of B. subtilis. Hybridization of deoxyribonucleic acid (DNA) from B-3275 with that of the strains of B. pumilus showed a binding efficiency (compared with the homologous reaction) of 58 to 99%, depending on the strain. Hybridization with the DNA from any of the strains of B. subtilis did not exceed 24%. DNA from B-3275 was unable to transform two amino acid auxotrophic markers to prototrophy in a highly competent strain of B. subtilis 168. We conclude that B-3275 is a strain of B. pumilus which we designate as B. pumilus NRRL B-3275.

Frank E. Young

Papers

Deoxyribonucleic Acid Antibody: A Method to Detect Its Primary Interaction with Deoxyribonucleic Acid

Chromosomal Location of Genes Regulating Resistance to Bacteriophage in Bacillus subtilis

Competence in Bacillus subtilis Transformation System

Dynamic interactions between cell wall polymers, extracellular proteases and autolytic enzymes.

Identification of Bacillus subtilis NRRL B-3275 as a Strain of Bacillus pumilus