The Journal of Experimental Medicine

Alexander, H. E.; Rake, Geoffrey

doi: 10.1084/jem.65.3.317pmid: 19870603

Precipitin tests have been carried out on spinal fluid from cases of meningococcal and other forms of meningitis, with monovalent anti-meningococcus horse serum of high titer. Using such a test it has been possible within 2 hours to diagnose and type cases of Type I and Type II meningococcal meningitis. In a certain number of cases fluids which were negative when first drawn became positive after standing for 1 or 2 days at 37°C. or room temperature. In 9.5 per cent of all Type I cases the fluids did not become positive. Fluids from cases due to atypical meningococci may react with the type serum of the group to which they belong ( i.e ., Types II* and VII, which belong to group II, with Type II serum) but do not in every case. Fluids from forms of meningitis other than meningococcal give no reaction. The use of concentrated sera is not advantageous at present, owing to the heterologous reactions which occur. Footnotes Submitted: 27 August 1936

Shwartzman, Gregory; Morell, Sam; Sobotka, Harry

doi: 10.1084/jem.65.3.323pmid: 19870604

A quantitative biological assay of the products obtained from the dialysis of B. typhosus , meningococcus, and B. coli culture filtrates has been undertaken. It was found that the active principles of the phenomenon of local skin reactivity to bacterial filtrates were retained by cellophane membranes. An appreciable purification was thus effected, amounting, on the average, to about a threefold increase in reacting potency per milligram of dry weight and of nitrogen. Attempts to purify bacterial filtrates by the fractional precipitation of their concentrates with dilute alkali, acid, and alcohol were unsuccessful. Footnotes Submitted: 13 November 1936

Fierz, H. E.; Jadassohn, W.; Stoll, W.

doi: 10.1084/jem.65.3.339pmid: 19870605

Injection of sodium atoxyl-diazoamino-sulfoanthranilate into guinea pigs produces an anaphylactic hypersensitiveness to the corresponding azoprotein (Schultz-Dale test). This leads to the conclusion that the injected sodium atoxyl-diazoamino-sulfoanthranilate first decomposes and then couples in vivo with the body protein to form the corresponding azoprotein and that therefore it is this compound, produced within the organism itself, which sensitizes. Footnotes Submitted: 23 September 1936

McMaster, Philip D.

doi: 10.1084/jem.65.3.347pmid: 19870606

Vital dyes injected intradermally enter lymphatic capillaries directly, rendering them visible, and appear later in the draining lymphatic trunks as colored streamers. The method enables one to perceive the state of the lymphatic channels and the rate of lymph flow within them. It yields consistent results when tested under physiological conditions known to increase or decrease lymph flow. In the horizontally placed normal limb at rest there is slight lymph flow. In a normal leg or arm hanging downward lymph flow ceases although fluid in the limb increases. When a previously dependent arm is raised above the head, or when the foot of a seated subject is propped on a table, lymph flow in the raised limb becomes active. It ceases in the skin of an arm subjected to partial obstruction of the veins by pressure from without, but very active lymph flow appears during the reactive hyperemia which follows upon the release of venous obstruction. It is still greater following release of total circulatory obstruction, and seems to be the same whether or not the limb has previously been engorged with blood. In the ischemic patches which appear in the skin of a limb during total circulatory obstruction (Bier's spots) the lymphatic capillaries are definitely and considerably constricted, whereas they are slightly dilated in the purple, congested regions of the skin round about. On release of obstruction there occurs a strikingly rapid, equal lymphatic drainage from both regions. The significance of all the findings is discussed. When dye is injected intradermally and the skin sucked, much of the foreign material is driven into the lymphatics draining the injected area. Footnotes Submitted: 24 April 1936

McMaster, Philip D.

doi: 10.1084/jem.65.3.373pmid: 19870607

Local intradermal injections of dye have disclosed the fact that the skin lymphatics in regions of cardiac edema are patent, full of fluid and much widened. Intercommunication between them is ready and dye escapes from them more rapidly than from the vessels of normal skin. A retrograde distribution of dye by way of the lymphatics often occurs and it may pass unseen along the deeper channels to emerge in the skin at unexpected, distant situations. A valvular incompetence of the lymphatics consequent on dilatation would appear to be the cause of these phenomena. In regions of cardiac edema lymph stagnates, despite the fact that the channels are open. In nephritic edema the lymphatic capillaries are wider than normal but not as wide as in cardiac edema. No sign of incompetency of the valves is to be observed. Instead lymph flow is considerably greater than normal, even when edema fluid is accumulating. It was noted to be greater in the periods of fluid equilibrium also and extraordinarily rapid in periods of diuresis. Footnotes Submitted: 24 April 1936

Heidelberger, Michael; Pedersen, Kai O.

doi: 10.1084/jem.65.3.393pmid: 19870608

1. Highly purified rabbit Type III pneumococcus anticarbohydrate proved to be homogeneous in the ultracentrifuge and its sedimentation constant, 7.0·10 –13 , did not differ from that of the principal component of normal rabbit globulin or of immune rabbit globulin containing up to 50 per cent of anti-egg albumin. The molecular weight of antibody in the rabbit is therefore probably very close to that of the principal normal globulin component, namely, 150,000. 2. Highly purified horse Type I pneumococcus anticarbohydrate, on the other hand, was only homogeneous in the ultracentrifuge when prepared from sera stored without preservative. Its sedimentation constant, 18.4·10 –13 , coincided with that of the principal globulin component in most of the Felton solutions and purified antibody solutions studied. The molecular weight of pneumococcus anticarbohydrate in the horse is probably three to four times that of the principal normal globulin component. 3. The significance of the differences between pneumococcus anticarbohydrate formed in the rabbit and in the horse is discussed. 4. Results are given of ultracentrifuge studies on the molecular species in solutions of egg albumin-anti-egg albumin specific precipitates dissolved in excess egg albumin. The implications of the results are discussed. Footnotes Submitted: 16 November 1936

Melville, K. I.

doi: 10.1084/jem.65.3.415pmid: 19870609

A method is described for the quantitative extraction of posterior pituitary antidiuretic substance from blood with which it has been mixed in vitro and in vivo for experimental purposes. With this procedure, it is found that a similarly extractable active substance may be detected as a normal constituent of dog and human blood. The data obtained from the blood of normal pregnancies and several cases of early toxemia, do not indicate any causal relationship between the presence of this substance in the circulating blood and the early symptoms (hypertension, edema, albuminuria) of the toxemia of pregnancy. Footnotes Submitted: 1 November 1936

Madden, S. C.; Winslow, P. M.; Rowland, J. W.; Whipple, G. H.

doi: 10.1084/jem.65.3.431pmid: 19870610

When blood plasma proteins are depleted by bleeding, with return of washed red cells (plasmapheresis), it is possible to bring dogs to a steady state of low plasma protein in the circulation and a uniform plasma protein production on a basal diet. Such dogs become test subjects by which the effect of various factors on plasma protein regeneration can be measured. Dogs previously the subjects of plasmapheresis, during long rest periods appear to increase their stores of plasma protein building materials and their blood plasma protein concentrations above former normal levels. A sterile abscess (turpentine) induces a marked reduction in plasma protein regeneration in these test dogs consuming an ample basal diet. The sharp reduction during the initial 24 hours may in part reflect an extravasation of plasma protein into the injured tissue but there also appears to develop a true disturbance of the mechanism which produces plasma proteins. Digestive disturbances interfere seriously with plasma protein production. Whereas large quantities of live yeast upset digestion and form no plasma protein, autoclaved yeast is well utilized, having a potency ratio of 4.4. Amino acids have been tested inadequately. A mixture of cystine, glutamic acid, and glycine does seem to have a definite effect upon protein metabolism and plasma protein production. Iron, under the conditions of these experiments, does not influence the output of plasma proteins. Liver extract (parenteral) is also inert. The proteins of red blood cells when added to the diet are poorly utilized for plasma protein formation and show a potency ratio of only 10.1. Kidney protein added to the kidney basal diet shows a potency ratio of about 5 as compared with 4.6 for that basal diet. A digest of beef stomach and rice polishings shows a potency ratio of about 7.9. Dried powdered serum shows a potency ratio of 3.5, which is much less than fresh serum (2.6). Powdered thyroid fed in doses sufficient to accelerate body metabolism shows no distinct effect upon plasma protein production not attributable to the protein in the thyroid powder itself. Long periods (25 to 30 weeks) of plasma depletion and basal diet intake remove much protein from body fluids and tissues. Associated with this protein depletion the dog loses its appetite and may vomit some food. There is loss of hair, a tendency to skin ulceration, and a distinct lowering of resistance to infection. The plasma protein output may fall to fasting levels in spite of food intake sufficient to maintain weight. We believe this condition to be a deficiency state related to severe depletion of the essential protein matrix of the body cells. Footnotes Submitted: 3 December 1936

Knutti, R. E.; Erickson, C. C.; Madden, S. C.; Rekers, P. E.; Whipple, G. H.

doi: 10.1084/jem.65.3.455pmid: 19870611

Normal dogs and two Eck fistula dogs, receiving a daily diet containing an average of 1 gm. of vegetable protein per kilo of body weight, showed after average intervals of 7 to 9 weeks, slight decreases in amounts of circulating plasma protein (Table 21). A third Eck fistula dog under similar circumstances was unable to maintain its plasma protein concentration above the edema level. This dog by biopsy was shown to have an abnormal liver and the evidence indicated that the other organs were normal. The animal showed active thirst and diuresis as compared with controls (Table 25). This Eck fistula dog had less than one-tenth the capacity of the normal dog to form new plasma protein when various food proteins were added to the basal diet, and no significant quantitative differences in the relative potency of these foods (liver, kidney, heart muscle, soy bean, salmon) could be distinguished (Table 22). It appears that the liver abnormality is responsible for this abnormal reaction. This observation gives strong support to the thesis that the liver is actively concerned with fabrication of new plasma protein. Footnotes Submitted: 3 December 1936