Binding between components of the tubercle bacillus and humoral antibodies.

Studies were undertaken to find a substance or substances for use in primary binding types of tests to detect humoral antibodies in rabbits and monkeys exposed to the tubercle bacillus that would distinguish between strains of mycobacteria. The antigen employed was a component of the 5159 strain of Mycobacterium tuberculosis that was obtained following sonification, ultracentrifugation, electrophoresis, and elution from a preparative polyacrylamide column. When the antigen was labeled with (131)I, specific binding was observed in sera from immunized rabbits and BCG-protected rhesus monkeys by the radio-gel electrophoresis and ammonium sulfate tests. This component was partially characterized, and its major antigenic determinants were associated with anionic mucopolysaccharides. Electrophoretically at pH 8.3 it migrated anodally to albumin, its molecular weight was between 9,000 and 12,000, and it was soluble in 50% saturated ammonium sulfate. Binding to antibody was destroyed after treatment with Pronase, but not after DNase or RNase. Inhibition of the reaction, as measured by the ammonium sulfate test, between the (131)I-labeled component and antisera from rabbits that had been immunized with sonicated 5159 organisms, was studied. These experiments demonstrated a capacity to define subtle similarities and differences among different mycobacteria and mycobacterial components. Some microorganisms not clearly related to mycobacteria also partially inhibited this reaction, suggesting that they shared antigenic groups with the component derived from 5159 organisms. The studies described suggested the advisability of using direct primary tests and purified components of mycobacteria to differentiate further the antigenic groups between individual pathogenic mycobacteria and between pathogenic and nonpathogenic organisms.

Reaginic activity associated with IgG immunoglobulin.

Five human sera with reaginic activity to a number of allergens were fractionated using anion exchange chromatography. In each serum, fractions which contained detectable IgG and no detectable IgA had capacity to fix to skin and subsequently elicit a P-K reaction. Four of these sera had reaginic activity about equally distributed between fractions containing only IgG and fractions containing mixtures of IgG and IgA. A fifth serum contained reaginic activity to crystalline bovine serum albumin (BSA) and most of the activity was associated with the fraction which contained only IgG. This serum was extensively studied using a variety of techniques and it was confirmed that most of the reagin to BSA in this serum was in those fractions containing only IgG. Since reaginic activity can no longer be considered a unique property of IgA the implications of finding antibody with reaginic qualities in immunoglobulins other than IgA are discussed.

Acetylation of human serum albumin by acetylsalicylic acid.

Human serum albumin is acetylated when exposed to acetylsalicylic acid (aspirin) under physiologic conditions in vitro. Indications are that a similar phenomenon occurs in vivo after ingestion of aspirin.

Deoxyribonucleic acid antibody: a method to detect its primary interaction with deoxyribonucleic acid.

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.

Shared antigens between Mycobacterium bovis (BCG) and other bacterial species.

Antigens from Mycobacterium bovis and Listeria monocytogenes bind to serums from normal rabbits as well as from those immunized with unrelated bacteria, especially intracellular parasites. Binding is to the Fab portion of immunoglobulin G and is immunologically specific.

Structural changes in human serum albumin induced by ingestion of acetylsalicylic acid.

Acetylsalicylic acid (aspirin) acetylates human serum albumin under physiologic conditions in vitro. These investigations were done to determine whether this phenomenon occurs in vivo and to delineate the site(s) of acetylation on the albumin molecule. Albumin was reacted in vitro with aspirin labeled with (14)carbon at the acetyl-1 or the carboxyl carbon. The altered albumin was hydrolyzed with trypsin and peptide mapping performed. Albumin so treated contains a unique peptide, designated "A," and shows diminution of two normal peptides, designated "B" and "C." Peptide "A" is never seen in normal albumin. Amino acid analyses indicate that peptide "A" equals the sum of peptides "B" and "C." Furthermore all three peptides contain lysine but lack arginine. Thus peptide "A" is formed by the acetylation of a lysine residue which is normally susceptible to trypsin and yields peptides "B" and "C." Radioautography of the peptide maps show most of the acetyl-1-(14)C activity in peptide "A." This indicates that one of the lysine residues in this peptide is the preferential site for the transacetylation reaction. Peptide "A," used as a marker for acetylation, is found in albumin from patients who take aspirin but is not demonstrable in albumin from one of these patients while she was taking sodium salicylate. A transacetylation reaction between aspirin and human albumin occurs in vivo and is similar to that observed in vitro.

Serendipity and strategy in rapid innovation.

Innovation is to organizations what evolution is to organisms: it is how organizations adapt to environmental change and improve. Yet despite advances in our understanding of evolution, what drives innovation remains elusive. On the one hand, organizations invest heavily in systematic strategies to accelerate innovation. On the other, historical analysis and individual experience suggest that serendipity plays a significant role. To unify these perspectives, we analysed the mathematics of innovation as a search for designs across a universe of component building blocks. We tested our insights using data from language, gastronomy and technology. By measuring the number of makeable designs as we acquire components, we observed that the relative usefulness of different components can cross over time. When these crossovers are unanticipated, they appear to be the result of serendipity. But when we can predict crossovers in advance, they offer opportunities to strategically increase the growth of the product space.

Estimate for the fractal dimension of the Apollonian gasket in d dimensions.

We adapt a recent theory for the random close packing of polydisperse spheres in three dimensions [R. S. Farr and R. D. Groot, J. Chem. Phys. 131, 244104 (2009)] in order to predict the Hausdorff dimension dA of the Apollonian gasket in dimensions 2 and above. Our approximate results agree with published values in two and three dimensions to within 0.05% and 0.6%, respectively, and we provide predictions for dimensions 4-8.

Allergy-important advances in clinical medicine: platelet-activating factor.

The Scientific Board of the California Medical Association presents the following inventory of items of progress in allergy. Each item, in the judgment of a panel of knowledgeable physicians, has recently become reasonably firmly established, both as to scientific fact and important clinical significance. The items are presented in simple epitome and an authoritative reference, both to the item itself and to the subject as a whole, is generally given for those who may be unfamiliar with a particular item. The purpose is to assist busy practitioners, students, research workers or scholars to stay abreast of these items of progress in allergy that have recently achieved a substantial degree of authoritative acceptance, whether in their own field of special interest or another.The items of progress listed below were selected by the Advisory Panel to the Section on Allergy of the California Medical Association and the summaries were prepared under its direction.

Asthma in adults: the ambulatory patient.

Heterogeneity is the hallmark of adult asthma, and patients thus need individualized therapeutic programs. But there are unifying underlying mechanisms, understanding of which makes it easier to design the clinical stategy appropriate to each case.

Coping styles in asthma.

Some patients with asthma cope with their disease in ways that are deleterious to them. The coping styles used by these patients often were used by them before the onset of the asthma, but the asthma amplifies these styles, and the coping styles can amplify the asthma. There are striking similarities between these coping styles and those described in cancer victims. Like the latter, they may reflect denial, anger, bargaining, and depression. Recognition that patients are using these coping styles and appropriate intervention will prevent them from continuing to act in these self-destructive manners.