The Journal of Experimental Medicine

Hahn, P. F.; Bale, W. F.; Hettig, R. A.; Kamen, M. D.; Whipple, G. H.

doi: 10.1084/jem.70.5.443pmid: 19870921

Radioactive iron as ferrous gluconate given by vein enables us to study iron excretion in urine, bile, and feces. There is an initial extra output in urine and feces during a few days (3 to 15 days) following the iron injection and this may total 2 to 8 per cent of the injected iron. Following this initial reaction the urinary excretion of radio-iron drops to traces or even to zero. The feces always contain measurable amounts of radio-iron—in five dogs receiving 100 to 250 mg. of radio-iron the fecal excretion per day settled down to 0.05 to 0.4 mg. per day. Blood destruction (acetyl-phenylhydrazine) causes a definite increase in radio-iron eliminated in the feces (0.1 to 1.0 mg. per day). Probably most of this excess iron comes through the biliary tract (bile fistula). The bile under usual conditions contributes very little iron to the intestine (0.01 mg. radio-iron per day or less). The body controls its iron stores by absorption or lack of it rather than by its capacity to eliminate it. The evidence is overwhelming that the dog excretes iron with difficulty and in small amounts (even in the plethoric state) by means of the biliary and gastro-intestinal tracts. Footnotes Submitted: 6 August 1939

Penner, Abraham; Bernheim, Alice Ida

doi: 10.1084/jem.70.5.453pmid: 19870922

We have attempted to reproduce in animal experiments a group of pathological findings which we have observed to be associated with shock. In order to simulate the compensatory vasomotor reactions occurring in shock, we have utilized the intraperitoneal injection of adrenalin hydrochloride in dogs, cats, rabbits and guinea pigs. That the effect of adrenalin hydrochloride when injected by this route is of long duration has been shown by the prolonged hyperglycemia which it produces. Our experiments have resulted in the production of a lesion in the digestive tract which is identical in the gross with those which we observed in our human material. The histological changes, however, have been found to differ from those encountered in the latter. These differences have been noted to occur only in the dog and cat, where the initial changes take place in the mucosa, and the alterations in the submucosa appear secondary to these. In the rabbit and guinea pig the histogenesis of the lesions is identical with that observed in man, the lesions first manifesting themselves in changes in the submucosa, congestion, edema and hernorrhage. Only later are similar changes seen in the mucosa, progressing finally to necrosis and ulceration. The cause of the histological differences has been found in the presence of arteriovenous anastomoses which occur in the submucosa in the case of the dog and cat and in the mucosa in the case of the rabbit, guinea pig and man. We have pointed out that variations in blood flow through the intestinal wall may result from the short circuiting of the blood through the arteriovenous anastomoses. This, associated with the vasoconstriction known to occur in shock, may if severe and prolonged, result in necrosis of the intestinal wall. We have experimentally reproduced the same lesion by the injection of adrenalin, which acts in a similar way. The experimentally produced anatomical changes offer additional evidence in support of the clinical occurrence of a vasospasm which is of sufficient severity and duration to cause tissue necrosis. Footnotes Submitted: 11 August 1939

MacFadyen, Douglas A.; Murphy, James B.

doi: 10.1084/jem.70.5.461pmid: 19870923

1. A design of experiments and technical procedure is described for the study of interference with transplantable tissue growth by test agents. The methods are guided by the principle of randomization and are based on the pairing of test and control in each host. 2. A system of analysis, employing well known statistical measures, is applied to results obtained with these methods and shows that they lead to consistently reproducible results. 3. A simple analytical method is proposed for correlating results obtained with different kinds of transplantable tissue in different strains of animals. This method is based on the condensation of an extended frequency distribution of events in control series of cases into a three category array of a normal frequency distribution. The three categories of test action are the inhibitory, the ineffectual, and the accelerative. Footnotes Submitted: 10 August 1939

MacFadyen, D. A.; Sturm, Ernest; Murphy, James B.

doi: 10.1084/jem.70.5.475pmid: 19870924

1. Mammary tissue of pregnant rabbits is found to contain an agent which inhibits the growth of Bashford Adenocarcinoma 63 in mice but this material is without effect on the Crocker Sarcoma 180. 2. Of the tissues so far studied the mammary gland of rabbits has yielded the most active product. 3. From the results it is probable that pregnancy enhances the production of the agent but this cannot be considered as established beyond doubt. 4. The factor is found, with diminished activity, only in the protein fraction obtained from the aqueous extract by full saturation with ammonium sulfate. Footnotes Submitted: 10 August 1939

Buddingh, G. John; Polk, Alice D.

doi: 10.1084/jem.70.5.485pmid: 19870925

1. A strain of meningococci obtained directly from the spinal fluid of a patient has been propagated in serial passage in 10 to 12 day old chick embryos without change in its essential characteristics. 2. The chick embryo is susceptible to infection with the meningococcus, and, depending on its stage of development, reacts to the infection with more or less specific lesions. 3. In chick embryos of 15 days incubation, following the utilization of definite portals of entry, such as the nasopharynx, or by inoculation of the amniotic fluid or by inoculation of the body wall, the meningococcus is localized in specific areas, namely in the cranial sinuses, the lungs or meninges, or in all of these areas. 4. The lesions of the meningococcus infection in man, a septicemia, sinusitis, pneumonia and meningitis can be reproduced in the chick embryo by choosing embryos at the proper state of development and utilizing the various portals of entry experimentally available. Footnotes Submitted: 6 August 1939

Buddingh, G. John; Polk, Alice D.

doi: 10.1084/jem.70.5.499pmid: 19870926

1. A microscopic and bacteriological analysis of the meningitis produced in the chick embryo following inoculation of meningococci into the body wall or into the amniotic cavity indicates that the meninges are invaded by way of the blood stream. 2. There is no indication that a direct extension of the infection by way of the middle ear, the cranial sinuses or the pia-arachnoid sheath of the olfactory nerves to the meninges takes place. Footnotes Submitted: 6 August 1939

Buddingh, G. John; Polk, Alice D.

doi: 10.1084/jem.70.5.511pmid: 19870927

1. 14 day old chick embryos are protected against subsequent meningococcus infection through the amniotic route by the intravenous administration of an homologous antiserum produced in hens, by a commercial concentrated polyvalent meningococcus antiserum and by a commercial meningococcus antitoxin. 2. Titrations of the different antisera indicate that the homologous and commercial polyvalent sera have approximately the same protective value and are much more effective than the commercial antitoxin. The titrations also show that the chick embryo is a sensitive indicator of the amount of antibodies present in a given amount of serum. 3. The mechanism of the protective action of the antisera is not apparent from these experiments except that in the treated embryos there is a relative inhibition of the growth and presumably a neutralization of the injurious products of the meningococci. Footnotes Submitted: 6 August 1939

Page, Irvine H.

doi: 10.1084/jem.70.5.521pmid: 19870928

1. Tachyphylaxis occurs when renin is repeatedly injected into dogs and cats regardless of whether they are normal, anesthetized, pithed, hepatectomized, suprarenalectomized, nephrectomized, or eviscerated. 2. The pressor response to renin in brief experiments is independent of the height of the arterial pressure or the presence of the suprarenals. Evisceration and large doses of ergotamine reduce the response. It is largely uninfluenced by pithing, intracisternal injection of renin, cocaine, strychnine, caffeine, and infusion of sodium bicarbonate or hydrochloric acid. It may be slightly increased by large blood transfusions or hepatectomy but the result is short lived. 3. There is no parallelism between the pressor responses to carotid sinus stimulation, adrenine, and tyramine on the one hand and renin on the other. 4. Section of the brain may be followed by depressor responses to renin. 5. Intracisternal injection of renin elicits no significant rise in blood pressure or other circulatory manifestations. 6. Continuous infusion of renin produces a prolonged rise of arterial pressure in normal and chronically suprarenalectomized dogs, but the pressure ultimately falls despite continued infusion. 7. Tachyphylaxis develops in the isolated rabbit's ear perfused with blood and small doses of renin. The same blood perfused through a second ear causes no vasoconstriction when renin is added. Addition of renin-activator restores the ability of renin to cause constriction. 8. Renin alone causes no vasoconstriction when perfused with Ringer's solution, but renin plus renin-activator restores activity. Tachyphylaxis does not develop when Ringer's solution is employed instead of recirculating blood. 9. Blood from animals made tachyphylactic by repeated injections of renin is lacking in activator and also fails to cause vasoconstriction in the rabbit's ear when renin and renin-activator are added. 10. Renin-activator is lost and tachyphylaxis develops more slowly during continuous infusion of renin. Blood pressure may fall after a period of renin infusion despite the pressure in the blood of excess renin. Injection of partially purified activator restores the activator content of the blood as demonstrated in the rabbit's ear, but no rise in arterial pressure occurs. Footnotes Submitted: 6 August 1939