The Journal of Experimental Medicine

Wishart, F. O.; Craigie, James

doi: 10.1084/jem.64.6.831pmid: 19870572

Observations on antibody production in the rabbit in response to the injection of the LS antigen of vaccinia have shown that this antigen retains its ability to stimulate the production of L and S antibodies, not only when it is in a state of solution as found in lapine Seitz filtrates, but also after it has been partially purified. As reported in previous papers, both the L and S antibodies participate ( a ) in the true agglutination of washed elementary bodies, ( b ) in the precipitation of the soluble LS antigen found in fresh vaccine suspensions or dissociated in vitro from washed elementary bodies. The difference in the thermostability of the L and S components of the LS antigen as far as their reactivity in vitro is concerned, holds in respect of their capacity to stimulate antibody production. Heating at 70°C. invariably abolishes the antigenicity of the L component while the S component remains antigenic after being heated to 90°C. Footnotes Submitted: 23 June 1936

Chow, Bacon F.

doi: 10.1084/jem.64.6.843pmid: 19870573

A type specific polysaccharide has been isolated from the autolyzed broth of Type I Pneumococcus by a modified Avery and Goebel's method. The newly prepared polysaccharide reacts with the homologous immune rabbit serum which has been completely absorbed with the acetyl polysaccharide of Avery and Goebel. The newly prepared polysaccharide produces passive immunity in mice and rats and possibly in rabbits. The antigenicity is not lost on boiling in acid or alkaline medium, but the precipitative activity is decreased. In conclusion, it has been shown that the polysaccharide from Type I Pneumococcus, as isolated by a slight modification of Avery and Goebel's method, is a more complete antigen. Footnotes Submitted: 28 June 1936

Horsfall, Frank L.; Goodner, Kenneth

doi: 10.1084/jem.64.6.855pmid: 19870574

1. Complete lipid patterns of specific precipitates from horse and rabbit Type I antipneumococcus sera, as well as of the sera themselves, have been determined by gasometric micro methods. 2. The lipid patterns of horse and rabbit antisera are very similar, and as regards the phosphatide fractions are relatively identical. 3. The lipid patterns of specific precipitates from horse and rabbit antisera show one outstanding qualitative difference. The specific precipitate from horse antiserum contains an amino phosphatide, which is probably cephalin, while that from rabbit antiserum contains a non-amino phosphatide, which is thought to be lecithin. Footnotes Submitted: 25 June 1936

Melnick, Daniel; Cowgill, George R.

doi: 10.1084/jem.64.6.865pmid: 19870575

1. A special apparatus and technique are described which permit one to conduct plasmapheresis quantitatively. 2. The validity of the methods employed, for determining serum protein concentration and blood volume as prerequisites for the calculation of the amount of blood to be withdrawn, are discussed. Footnotes Submitted: 5 July 1936

Melnick, Daniel; Cowgill, George R.; Burack, Ethel

doi: 10.1084/jem.64.6.877pmid: 19870576

1. From a consideration of previous work related to the problem of the influence of diet upon the regeneration of serum protein, a plan of study is described which eliminates the many variables shown to be operating in the studies conducted by these pioneer workers. 2. By the administration of a protein-free diet at a high level of caloric intake to the dog subjected to plasmapheresis during which one-fourth of the blood volume of the animal is withdrawn daily, it is possible to reduce the serum protein concentration to the basal level (3.5 to 4.2 per cent) and to deplete the organism of its reserve stores of this protein within 1 week. The subsequent week has been demonstrated to be an equilibrium period. 3. The dog contains a reserve store of serum protein building material equivalent to about 30 to 40 per cent of the total amount normally present in the circulation. 4. When fed the protein-free diet and when subjected to quantitative plasmapheresis, whereby the basal level of the serum protein concentration is maintained constant, the dog is able in 1 week to regenerate approximately 20 to 30 per cent of the total amount of this blood protein normally present in the plasma. 5. The administration of a diet favorable for promoting the regeneration of serum protein requires approximately 4 to 5 days before a constant and maximal response to the dietary stimulus is obtained. Equilibrium data are yielded during the 2nd week, and these are employed in calculating the potency ratio of the dietary protein. Footnotes Submitted: 5 July 1936

Melnick, Daniel; Cowgill, George R.; Burack, Ethel

doi: 10.1084/jem.64.6.897pmid: 19870577

1. By the technique of quantitative plasmapheresis the effects of single proteins in artificial synthetic diets were studied with respect to their value in promoting the regeneration of serum protein. 2. The ratio of ( a ) the amount of serum protein per week removed by bleeding above that regenerated by the dog when eating the protein-free diet, to ( b ) the dietary protein increment ( i.e ., above that required for nitrogen equilibrium) was termed the potency ratio. The results indicated that serum protein was slightly superior to casein and lactalbumin in promoting the regeneration of serum protein. However, the respective potency ratios, varying from approximately 0.51 to 0.36, were comparable and not widely divergent as those reported by others. It was concluded that, whereas in some individuals dietary proteins may be able to produce a significant increase in the serum protein concentration, the potency ratios are not sufficiently different to warrant the administration of any one protein in preference to another. 3. The inhibitory effect of the basal protein-free diet with respect to serum protein regeneration in the dog was also demonstrated by the inability of the protein concentration to attain the normal level in spite of discontinued plasmapheresis. However, a subsequent fasting period resulted in a progressive rise in the serum protein concentration until the normal value was approximated. These observations are interpreted as indicating that the products of tissue protein catabolism can be utilized in the formation of new serum protein. 4. The experimental production of what seems to be an inhibition of the serum protein regenerating mechanism was described. This observation together with the hypothetical evidence presented by Bloomfield (17) and Weech and his associates (9) suggests that the most profitable line of approach to solution of the problem of hypoproteinemia lies not so much in the evaluation of dietary factors but in finding a way for stimulating internally the serum protein regenerating mechanism, which seems to involve in some manner the capacity of the tissue to furnish protein for the needs of the plasma. 5. A hypothesis explaining the mechanisms responsible for serum protein formation was presented and the experimental support for it discussed. The rôle of tissue protein catabolism in this function was emphasized. Footnotes Submitted: 5 July 1936

Smadel, Joseph E.

doi: 10.1084/jem.64.6.921pmid: 19870578

Nephritis can be induced in rats by the injection of anti-kidney sera obtained from rabbits immunized with suspensions of perfused rat kidney. Anti-kidney sera, thus prepared, contain a number of antibodies capable, on injection into rats, of inducing a severe anaphylactoid reaction with general vascular manifestations that involve the kidney as well as other organs. These sera also contain a nephrotoxic agent that affects the kidney primarily. The nephrotoxic effect is characterized clinically by severe persistent albuminuria with casts, and transient anasarca during the acute disease, but no significant hematuria occurs. When a severe anaphylactoid reaction is superimposed on the nephrotoxic injury, hematuria is an outstanding feature. Nephrotoxin is demonstrable in vivo and is not related quantitatively to the precipitins in the anti-kidney serum against kidney extract. It is most readily obtained by immunization with kidney suspensions, but may occasionally appear after injections of other organ preparations; it does not result from immunization with erythrocytes or serum. Nephrotoxin is present in the globulin fraction of anti-kidney serum. The nephrotoxic action of anti-kidney serum is easily removed by absorption with kidney cells or fat-free kidney tissue. Similar preparations of liver likewise remove it, but less readily. Neither kidney, liver, or brain lipids affect it, nor does absorption with red blood cells or serum. Nephrotoxin appears to be an antibody that is relatively organ specific in its affinities. It differs from the more common antibodies involved in reverse anaphylaxis in one respect, at least: The animal rapidly becomes desensitized against the latter and fails to react, whereas desensitization to nephrotoxin is difficult to secure. Footnotes Submitted: 29 June 1936

Moen, Johannes K.

doi: 10.1084/jem.64.6.943pmid: 19870579

1. Mononuclear exudative cells, obtained from tuberculous guinea pigs by the intrapleural injection of parowax, exhibited characteristic sensitivity to the toxic action of tuberculin when tested in tissue culture. 2. Experiments with these cells, practically free of body fluids, show conclusively that sensitivity to tuberculin is an inherent characteristic of mesenchymal cells from tuberculous animals. 3. Fibroblastic growths which developed from mononuclear exudative cells derived from a tuberculous animal showed persistence of sensitivity to the toxic action of tuberculin on repeated transplantations over a prolonged period in vitro . Footnotes Submitted: 29 June 1936

Weld, Julia T.; Gilder, Helena

doi: 10.1084/jem.64.6.953pmid: 19870580

1. In rabbits, guinea pigs, and mice pneumococcus autolysate antitoxin has no effect against generalized infection by the pneumococcus. 2. In a large proportion of cases of pneumonia and sepsis caused by the intratracheal inoculation of large amounts of living pneumococci in normal or sensitized guinea pigs, autolysate antitoxin saves the animal. 3. The autolysate antitoxin is protective in most cases of pneumonia and sepsis caused by the intratracheal inoculation of small amounts of living pneumococci combined with sublethal doses of staphylococcus toxin. 4. These experiments indicate that in pneumococcus pneumonia of guinea pigs the autolysate toxin or toxins are elaborated only in the lungs. Footnotes Submitted: 7 July 1936

Pappenheimer, Alwin M.

doi: 10.1084/jem.64.6.965pmid: 19870581

Reduction of renal tissue in young rats regularly leads to a marked increase in the volume of the parathyroid glands. If partially nephrectomized rats are maintained on a low calcium diet, growth is stunted, and skeletal lesions are produced, of far greater severity than can be ascribed to the dietary calcium deficiency alone. The picture closely resembles that found in cases of renal rickets in children. Footnotes Submitted: 9 July 1936