Extreme hyponatremia in patients with myelomatosis: an effect of cationic paraproteins.

Three patients with IgG myelomatosis and extreme hyponatremia are described. By isoelectric focusing of the M-component it is demonstrated that the subnormal sodium value is most likely explained by a cationic effect of the myeloma globulin.

Pleuroperimyocarditis caused by immunization with anticatarrh vaccine. A case report.

A case of pleuroperimyocarditis caused by immunization with anticatarrh vaccine is described. During the most acute phase, circulating immune complexes were demonstrated in the patient's serum. The possibility that these complexes represent a pathogenic mechanism in the illness and the value of anticatarrh vaccination are discussed.

A survey for circulating immune complexes in patients with acute myocardial infarction. Use of a C1q-binding assay with soluble protein A as indicator.

A new assay for the detection of circulating C1q-binding immune complexes (IC) is described. The assay makes use of solid-phase C1q and iodinated soluble protein A, extracted from the cell wall of Staphylococcus aureus. In a model system the assay could detect heat-aggregated IgG down to a concentration of about 50 ng/ml. This method and three other assays, previously described, were used to survey the appearance of IC activity in sera from hospitalized patients with acute myocardial infarction. Depending on the assay system used, from 56% to 66% of the patients investigated were found to develop circulating IC. The earliest appearance of circulating IC was noted 5 days after infarction. The highest incidence of positive reactions and the strongest reactions occurred 2 to 3 weeks after hospitalization; thereafter the IC positiveness tapered off, and all patients were negative 6 weeks after infarction.

Extreme elevation of transaminase levels in acute heart disease-a problem in differential diagnosis?

Five patients admitted to the Coronary Care Unit at the Department of Medicine, Serafimerlasarettet, who developed extreme elevation of transaminase levels, are discussed in terms of problems in differential diagnosis. All five had manifest right ventricular failure on admission and four also had hypotension. Three of the patients died, two survived. The three post-mortem examinations showed extensive infarctions of the left ventricle and septum. The two survivors had had a prolonged ventricular tachycardia and a probable silent infarct, respectively. It is concluded that the extremely high transaminase levels sometimes seen in acute cardiac disease are predominantly due to sizeable amounts released by the liver as a result of central necrosis of the liver cells. The probable prerequisite for the development of central necrosis of the liver in acute cardiac disease is usually the combination of right ventricular failure and hypotension, which in turn are most often due to extensive left ventricular infarcts.

Further studies on the ultrastructure of dimeric IgA of human origin.

Human colostral IgA and myeloma dimer IgA were purified and examined in the electron microscope using a modified technique of negative staining. Both types of preparation contained double Y-shaped structures of the dimensions: Fab region, 35 x 70 A, and the sum of the two Fc regions, 40 x 140-155 A. Colostral IgA as well as myeloma dimer IgA molecules showed a tendency of bending at the point where the Fc regions joined. Secretory component bound to dimer IgA produced no visible alteration of the molecule. Mild reduction and alkylation of colostral IgA yielded single Y-shaped 7S monomers with the dimensions, Fab, 35 x 70 A, and Fc, 40 x 65-70 A.

Ultrastructure of secretory and high-polymer serum immunoglobulin A of human and rabbit origin.

Electron micrographs of immunoglobulins A from human and rabbit colostrum, which were purified on tall agarose columns, revealed Y-shaped molecules (125 by 140 angstroms). The linear dimensions of the arms were 55 to 75 by 25 to 30 angstroms. A molecular model is postulated in which two immunoglobulin A monomers are superimposed on each other in a close-packed state with the secretory piece inserted in the constant region of the alpha-chains. High-polymer (11 or 13S) immunoglobulin A molecules (total span 100 to 110 angstroms) from human serum were composed of four arms (50 to 55 by 20 angstroms) joined at a contrast-rich center.

Ultrastructure of papain and pepsin digestion fragments of human IgM globulins.

The ultrastructure of papain and pepsin-digested products of human IgM globulins has been analyzed. Papain digestion was performed both in the presence and absence of cysteine. The Fcmicro fragment was found to represent the central ring structure in the intact IgM molecule, plus a minor part of the appendages extending from the ring. The Fcmicro ring structure was occasionally seen to be composed of dimers of short rods, probably identical with the endpieces of two micro-chains. Such dimeric structures, released from the intact Fcmicro rings, had a tendency to aggregate sidewise, producing complexes of varying size. The dimensions of the Fcmicro fragments were: outer diameter approximately 85 A, inner diameter about 40 A. The length of the protrusions varied from 20-30 A. The Fabmicro preparations contained long strands of sidewise aggregated, short rod-shaped fragments. No aggregates were seen in the F(ab'')(2)micro preparations. The two Fab''micro units in the dimeric F(ab'')(2)micro fragments were usually parallel to each other. The dimensions of the Fabmicro and F(ab'')(2)micro fragments were 50-80 A x 30 A and 75-80 A x 55 A, respectively. These findings provide morphological evidence that the C-terminal ends of the micro-chains (the Fcmicro fragment) make up the central ring structure in the IgM molecule. They further indicate that the F(ab'')(2)micro fragments constitute about (3/4) of the appendages extending from this ring structure.

The ultrastructure of human thyroglobulin.

Thyroglobulin molecules purified in a single step procedure by gel filtration were studied in the electron microscope using the negative staining technique. The molecule had the shape of a flexible helix with two turns. Its length was about 220 A and the maximal diameter of the coiled part of the molecule was estimated to be 110 A. The pitch varied between 40 and 50 A. Thyroglobulin molecules dried in sodium tungstosilicate on a carbon film as for electron microscopy retained their hemagglutination-inhibiting activity and 19S sedimentation constant when redissolved in physiological buffer.

Ultrastructural studies of human and rabbit alpha-M-globulins.

Electron micrographs of isolated human alpha(2)M-molecules, obtained by the negative contrast technique, revealed morphologically homogenous structures resembling a graceful monogram of the two letters H and I. The modal values for the length and width of the alpha(2)M particles were 170 A and 100 A, respectively. Purified rabbit alphamacroglobulins contained about 80% alpha(1)M- and 20% alpha(2)M-globulins. The isolated rabbit alpha(1)M- and alpha(2)M-molecules were morphologically indistinguishable from one another and from human alpha(2)M-molecules. Preliminary immunoprecipitation studies demonstrated that the two rabbit alphaM-globulins were antigenically different. Sedimentation constant determinations gave s(20, w) values of 18.8 and 18.2 for rabbit alpha(1)M and alpha(2)M, respectively.

The ultrastructure of normal and pathological IgM immunoglobulins.

Free IgM immunoglobulins were examined in the electron microscope using the negative contrast technique. Normal human and rabbit IgM and Waldenström macroglobulins were indistinguishable from one another and revealed flexible spider-like particles with five appendages joining a central ring. The average total span of the molecules was 300 A. The appendages were about 125 x 30 A; the central ring had an outer diameter of approximately 100 A and an inner diameter of 40 A. Some purified 19S IgM preparations tended to form massive aggregates (>/=50S) which, when examined in the electron microscope, revealed enormous clumps of IgM molecules whose appendages were entangled with one another. Electron microscopy of reduced-alkylated IgM revealed total absence of intact spider-like molecules. The predominating structure observed was a round electron-dense knob about 50 A in diameter which in some cases had a fine fiber-like extension with approximate dimensions 100 x 15 A. Rabbit and human IgM molecules with antibody activity to poliovirus dried in sodium tungstosilicate on a carbon film as in preparation for electron microscopy were shown to retain nearly 100% of their poliovirus neutralizing activity after redissolving in a physiological buffer.