Abstract: A Gram-positive, spore-bearing, aerobic bacillus, capable of lyzing the living cells of many Gram-positive microbial species, has been isolated from soil. Cultures of this soil bacillus in peptone media release during autolysis a soluble agent which exerts a bactericidal effect on all the Gram-positive microorganisms so far tested, and inactivates their glucose dehydrogenases. It also inhibits the growth of the susceptible species in culture media. Several of the Gram-positive species undergo lysis when incubated with the bactericidal agent. It appears however, that lysis is only a secondary process, due to the autolytic enzymes of the susceptible cells, and that it follows upon some other primary injury caused by the active agent. The bactericidal agent is ineffective against all the Gram-negative bacilli so far tested.

Abstract: In the first paper of this series, a description was given of a cell-free extract, obtained from autolysates of a particular strain of a soil bacillus, which selectively inhibits the growth of all the Gram-positive microorganisms so far tested, and exerts on them a bactericidal effect in vitro. In the present study it is shown that the same agent protects white mice against infection with large numbers of virulent pneumococci. It also exerts a curative effect when administered to mice several hours after injection of the infecting organisms. The degree of protection afforded, and the minimal effective dose of bactericidal agent, are approximately the same for all virulent pneumococci, irrespective of type specificity. The bactericidal agent is entirely ineffective against infection with virulent Friediander bacilli (type B). This agrees with the fact that the agent does not affect Gram-negative bacilli in vitro. The protective action exerted by the bactericidal agent against experimental pneumococcus infection depends upon the same mechanism which determines its bactericidal effect in vitro.

Abstract: 1. The use of an antigen which can be seen within cells demonstrates that one may stimulate the phagocytic cells either of the liver and spleen or of the tissues and lymph nodes to produce antibodies. 2. The appearance of antibodies in the serum correlates with the time when the dye-protein is no longer visible within the cells and with the phenomenon of a partial shedding of their surface films. 3. It is thus inferred that the cells of the reticulo-endothelial system normally produce globulin and that antibody globulin represents the synthesis of a new kind of protein under the influence of an antigen. 4. An antigen is a substance which can specifically modify the synthesis of the cytoplasm of the cells of the reticulo-endothelial system.

Abstract: 1. Highly purified preparations of homogeneous antibody can be made by the salt dissociation methods (6, 7) without any change in sedimentation due to the method of purification. 2. Antibodies prepared from sera of various animal species fall into two groups as regards molecular weight; in one group cow, horse, and pig, a heavy molecule of molecular weight 990,000 is formed; in human being, rabbit, and monkey, the molecular size is that of the normal gamma serum globulin. Both types of antibody molecules are either not compact or not spherical since the frictional ratios f/f(0) are 2.0 and 1.5 respectively. 3. Horse antibody shows an unchanged activity and sedimentation diagram between pH 3.44-9.06, although there is some aggregation at the more acid and some dissociation at the more alkaline pH. At pH 1.44 the antibody activity is unchanged but some breakdown of the molecule takes place. At pH 12.4 activity is destroyed and the molecule is completely broken down. 4. Some horse antibody preparations show evidence of breakdown of the antibody into inhomogeneous material on continued immunization over a long period.

Abstract: A simple isolation of the prostate enabled quantitative collection of prostatic secretion in dogs over periods of months. The secretory stimulant was pilocarpine and 2 similar amounts injected with a 6 hour interval gave smaller amounts at the second testing, suggesting a fatigue effect. The prostate was not absolutely refractory since doubling the amount of alkaloid injected at the second test increased the volume to equal or exceed the preliminary secretion. The depression effect had disappeared at 24 hours. In normal dogs the secretory curves were essentially regular, with occasional prolonged rises or depressions. The amount of secretion did not bear a direct relationship to the weight of the gland in adult dogs. The germinal epithelium of the testis underwent atrophy during the first few weeks of cage life while the prostatic secretion was maintained, showing that the atrophy was differential and did not involve the cells producing the androgenic hormone. The atrophy was reversible and all dogs kept for more than 4 months showed restoration of the germ cells. A few dogs developed atrophy of the germinal cells with cessation of prostatic secretion for many weeks but with final recovery. Removal of the suprarenal glands with suprarenal insufficiency did not produce sterility. The distribution of electrolytes in the prostatic secretion differed from that in the serum-transudate system, although the concentration of osmotically active substances was the same, being made up almost entirely of sodium and chloride. The distribution was not affected by the different physiological procedures used in this study. Protein concentrations were less than 1 per cent. The rate of prostatic atrophy following castration was determined, and cessation of secretion occurred in 7 to 23 days. The restoration of prostatic fluid in castrate dogs following daily injections of testosterone propionate followed a smooth curve to form a plateau which was interrupted occasionally by prolonged elevations with return to the established level. The prostate having been reconstructed, the dosage of androgenic material injected could be greatly reduced without causing a decrease in secretion. Ablation of the thyroid and parathyroid glands had no significant influence on prostatic secretion. Hyperthyroidism caused a secretory depression interrupted with returns to normal levels.

Abstract: A small mouse stock in which lymphocytic choriomeningitis is endemic has been observed over a period of 4 years. The disease has persisted during that time, but it has become so mild that it can no longer be recognized by clinical observation. In spite of this fact, all of the stock mice tested, both young and old, carried considerable amounts of virus in their organs and blood. The females readily transmit the infection to their offspring. Intrauterine infection has become the only mode of transmission of the disease in contrast to the situation in 1935 when a certain number of mice were born virus-free and became infected by contact shortly after birth. The present mildness of the disease appears to be due to two factors, namely, the change in its mode of transmission just mentioned, and a shift in the severity of the disease with regard to the age of the host at the time of infection. This shift has occurred gradually since 1935 when the mice infected in utero were the only ones to become sick. Since 1937, however, the virus is quite harmless for such animals and produces symptoms only in suckling mice from the virus-free stock exposed to contact infection. Evidence is presented which suggests that the shift in the severity of the disease was caused by a decrease of the pathogenicity of the virus for embryonic mouse tissue and a concurrent increase of the resistance to intrauterine infection of the mice from the infected stock. Another change noted concerned the communicability of the experimental disease. In contrast to observations made in 1935 the experimental infection of mature mice from the virus-free colony is now very rarely transmitted by contact to healthy mice, young or old. Suckling mice from the same stock infected by intranasal instillation of virus, however, readily transmit the disease and continue to do so as they grow up. The same is true for mice infected naturally. The reason for this discrepancy has not been ascertained, but it has been shown that naturally infected mice capable of transmitting the disease in general discharge large amounts of virus through the nose for a longer period of time than mature mice infected experimentally which fail to transmit their infection. It may likewise be of significance in this connection that the virus can lose its communicability by animal passage. A marked change (chiefly climatic and dietary) in the environmental conditions of the infected stock failed to influence the course and character of the epidemic.

Abstract: Acute nephritis of medium severity, affecting both glomeruli and tubules, was produced in rats by injections of anti-rat-kidney serum, given on 3 consecutive days. The course of the nephritis was markedly influenced by the type of diet which was fed. Rats tended to recover promptly from the induced nephritis when a low protein-high carbohydrate diet was given. On the other hand, in nephritic rats maintained on a medium protein diet the nephritis almost invariably became chronic and half the animals died of renal insufficiency during the 10½ months of observation. Finally none of the rats which received a high protein-low carbohydrate diet recovered from the acute renal injury; all developed chronic progressive nephritis and the majority died of renal failure after some months.

Abstract: In forty-eight rats kept on a basal diet deficient in the vitamin B complex and supplemented with vitamin B1 and riboflavin or with vitamin B1, riboflavin and vitamin B6, various pathological changes in the liver were observed. These changes were characterized mainly by parenchymatous and fatty degeneration, focal and massive necrosis, hyperemia and hernorrhage and, in some of the rats, by perilobular and condensation fibrosis. Addition of yeast or Peters' eluate (yeast extract) regularly prevented this hepatic injury. On the basis of the evidence obtained, it is assumed that the liver changes are of nutritional origin and should be correlated to deficiency of a part of the vitamin B2 complex.

Abstract: Experimental evidence shows that histamine is liberated when the upper layers of the skin are stimulated in the threshold range although no gross or microscopic evidence of tissue damage is demonstrable. A histamine-like substance is recoverable from the anterior chamber of the rabbit's eye on electrical stimulation of the cornea. This substance is liberated in direct proportion to the intensity of the stimulus. Histamine when injected intradermally or applied to the denuded skin (less epidermis and some cutis) or cornea causes pain. That the substance liberated is most likely histamine was shown by its action on the intestinal strip of the guinea pig, which action was not effaced by adding atropine to the bath; by its heat stability, its neutralization by histaminase and its dialysability through cellophane membranes, and by the fact that thymoxyethyldiethylamine, which appears to be a specific antagonist to histamine, neutralizes the action of the diffusates of stimulated skin and when injected subcutaneously or rectally abolishes generally the pain responses to pinching, pricking and cutting, and lowers the electrical threshold of the skin markedly without affecting the somatic sensory nerve trunks.

Abstract: A linear relationship exists between the logarithm of the quantity of epidemic influenza virus neutralized and the logarithm of the quantity of antiserum which is capable of achieving this result. This relationship is the same for the serum of a ferret convalescent from experimental influenza as for the serum of a rabbit immunized with the virus. By means of the linear relationship between virus and antiserum it is possible to determine a fixed, rather than a relative, value for the neutralizing capacity of a serum.

Abstract: Constriction of the aorta just above the origin of both main renal arteries invariably resulted in elevation of the carotid systolic and carotid mean pressure. The hypertension was not immediate, but developed in about the same time as after constriction of the main renal arteries (3). Constriction of the aorta just below the origin of both main renal arteries had no significant effect on the carotid systolic or carotid mean pressure. Since these results were first reported (1), Rytand (88, 89) has shown by an indirect method, namely, the demonstration of the development of cardiac hypertrophy, that hypertension in the upper part of the body can be produced in the rat by constriction of the aorta just above the origin of both main renal arteries. The immediate effect of constriction of the aorta either below or above the main renal arteries is a fall of blood pressure (femoral mean pressure) below the site of the clamp, the extent of the fall being directly dependent upon the degree of constriction of the aorta. Of particular interest is the eventual elevation of the femoral mean pressure above the normal in some animals with the aorta constricted or even occluded above the origin of the main renal arteries. This was most pronounced and persistent in those animals in which, in addition, the aorta below the origin of the renal arteries, and, in some animals, the main renal arteries, also were constricted. The most important factors which determined this elevation of blood pressure in the lower part of the body were probably increased flow of blood into the vascular bed below the clamp and peripheral vasoconstriction of renal and humoral origin, as in the case of the hypertension produced by constriction of the main renal arteries alone (2–86). Although elevation of the carotid systolic or carotid mean pressure occurred invariably within 24 to 48 hours after the constriction of the aorta above the site of origin of both main renal arteries, yet there was a tendency, after a variable period, for the elevated blood pressure to become lower or even to drop to the original level. Increased constriction, and finally occlusion of the aorta, above the origin of the main renal arteries, and even constriction or occlusion of the aorta below the renal arteries, in addition, failed to induce hypertension that persisted for a long time at a high level. In order to produce this effect, it was necessary to constrict the main renal arteries as well. The possible explanation of the failure of the hypertension to persist for a long time after constriction of the aorta alone, is that the initial ischemia of the kidneys disappeared due to the improvement of the blood flow through the kidneys as a result of (a) the increase of the natural accessory circulation to the kidneys; (b) the increased blood pressure above the site of the clamp and consequent increased flow of blood into the part of the aorta below the clamp; (c) increased pressure below the site of the clamp due, in great part, to peripheral vasoconstriction, and in part to the increased inflow of blood into the lower part of the body through the aorta and collateral channels. For the dog, this method is not necessary for the production of persistent hypertension. Constriction of the main renal arteries is easily performed and is effective for the production of generalized hypertension (2–11). However, constriction of the aorta in addition to constriction of the renal arteries results in greatly elevated persistent hypertension. Constriction of the aorta alone above the origin of the main renal arteries would be useful in the dog only for the production of relatively short periods of hypertension in the upper part of the body. For small animals it may be a more effective and useful method. In the dog, the only technical difficulty encountered was the erosion of the wall of the aorta by the clamp. This may not occur in small animals. In previous studies (2–11) that have dealt with the constriction of the main renal arteries, this accident rarely occurred. When the constriction of the aorta above the origin of the main renal arteries was of moderate degree, or was gradually made very great, the resultant hypertension was not accompanied by impairment of renal excretory function, as determined by urea clearance or by the quantity of urea, creatinine or non-protein nitrogen in the blood, the benign phase of hypertension (3). When the constriction of the aorta was suddenly made very great, impairment of the renal excretory function usually followed, and the animal developed fatal convulsive uremia and characteristic vascular lesions, the malignant phase of hypertension (9). These facts, are all indicative of the renal origin of the hypertension which results from the constriction of the aorta just above the origin of both main renal arteries. Hypertension did not persist for a sufficiently long time to permit any conclusive comparison between the effect of the high and low pressures on the structure of the vascular system, above and below the site of the clamp, respectively. During the period of survival of these animals, no significant differences were observed between the appearance of the vascular system of the upper part of the body and that of the lower part of the body, and significant cardiac hypertrophy did not develop. In the aorta and large arteries, intimal arteriosclerosis was not observed. In the aorta of one old animal several small plaques of calcification were found in the media, but these were present in the portion of the aorta below, as well as above the clamp, and they were no larger or more abundant than were observed in some old dogs with normal blood pressure. Dogs 3–50 and 3–83, that are still alive, with very high blood pressure above the site of the aortic clamps, and relatively low pressure (though greater than normal) below the site of the aortic clamps, will be valuable for the determination of possible differences between the effects of the two levels of blood pressure in the large and small blood vessels. In these dogs also, it will be possible to determine the effect of the persistently high blood pressure on the myocardium. The possible application of the results of this study to the problem of the pathogenesis of human eclampsia is mentioned here for consideration. Since this condition occurs in pregnancy only at a time when the uterus is greatly enlarged, it is at least possible that the mass may press on the aorta or both main renal arteries sufficiently to produce renal ischemia. The suddenness with which the uremic convulsive phase of eclampsia develops is in keeping with this idea. In the dog, an aggravating effect of pregnancy on an already established hypertension has not been noted. As a matter of fact, most of the hypertensive dogs that have become pregnant, have shown a slight or moderate fall, rather than an increased rise of pressure. Since the dog stands with the body in a horizontal position, and does not lie on its back, pressure of the pregnant uterus on the aorta and blood vessels is less than in human beings who stand erect and frequently lie on their backs. The soundness of this suggestion could be tested by placing pregnant women, in the early stage of eclampsia, in a position which could relieve possible pressure on the aorta and main renal arteries. A possible explanation of the fall of pressure in the pregnant hypertensive dogs is the compensatory effect of the normal kidneys of the pups, as in the case of an animal with one main renal artery constricted and the other kidney normal. As has been shown (3, 31, 72), the presence of one normal kidney in an animal hypertensive due to constriction of the other main renal artery, results, after a variable period, in a return of the blood pressure to normal. How the normal kidney acts to produce this effect is not known.

Abstract: Vascularization of the cornea of the rat in the absence of antecedent pathology is probably a specific and the most reliable criterion of riboflavin deficiency. Its initiation and repair may be used for testing the biological activity of compounds structurally related to riboflavin. The facts that the invading capillaries are easily visible in the living animal and that the growth and regression of the blood vessels are under dietary control and for a considerable period of time unaccompanied by other pathological reactions, make this method very suitable for the study of problems related to capillary growth. We believe that the best hypothesis in explanation is that the vascularization is a response to asphyxia of the tunica propria.

Abstract: 1. Tuberculous and vaccinated rabbits and guinea pigs mobilize mononuclear phagocytes at the site of a non-specific inflammation with greater rapidity than do normal animals, just as they respond to tubercle bacilli. 2. The succession of cells that characterizes inflammation in general is accelerated in allergic rabbits and guinea pigs in response to non specific irritants. 3. The pH at the site of reinfection with tubercie bacffli in immun ized rabbits and guinea pigs and at the site of a non-specific inflammation in the latter is slightly lower than in a similar site in a normal animal. 4. No constant relation was found between the mobifization of mononuclears and the hydrogen ion concentration at the site of inflammation. 5. The rate of mitotic and amitotic division of mononuclears in allergic rabbits and guinea pigs in response to non-specific irritants is greater than in normal animals. 6. Mononuclears derived from actively tuberculous or vaccinated guinea pigs exhibit greater in vitro phagocytic capacity for carbon particles than mononuclears obtained from normal animals. 7. Mononuclears of tuberculous rabbits ingest more staphylococci than the phagocytes of the same type originating from normal animals. 8. Mononuclears originating from actively tuberculous rabbits and guinea pigs exhibit greater in vitro phagocytic capacity for tuberde bacilli than mononuclears obtained from normal animals. 9. The enhancement of the phagocytic capacity for tubercie bacilli afforded mononuclears by vaccination with a bacillus of low virulence is lower, and of questionable significance. 10. The increased phagocytic activity of mononuclears derived from tuberculous or vaccinated rabbits and guinea pigs for tubercie bacilli and for non-specific particulate matter occurs in media containing sera derived from normal and from tuberculous individuals. 11. The more rapid mobilization of mononuclears by immunized animals in response to specific as well as non-specific irritants is associated with their increased physiological activity. The significance of this enhanced activity conferred by the tuberculous process on the mesenchyme cells is discussed in relation to the mechanism of immunity to tuberculosis and other phenomena.

Abstract: 1. The ratios between the rates of growth of the body and of the heart, kidneys, and liver are approximately uniform between 40 gm. body weight and the body weight at maturity in the albino rat. The male and female hearts grow at 0.75 times the rate of growth of the body, the male kidneys at 0.717 times, the female kidneys at 0.648 times, and the liver at 0.838 times the rate of growth of the body as a whole. 2. Formulas for the prediction of organ weight from body weight were derived from the data on 1591 albino rats kept under constant conditions. 3. A series of experiments in which dietetic and metabolic variables were introduced into otherwise constant conditions showed that the heart weight was not affected by diet, and that both kidney weight and weight of liver protein (used as a measure of effective liver size) varied in the direction of change in the protein content of the diet. Decrease in rate of metabolism induced by thyroidectomy and increase in metabolism following the administration of thyroxin led to a corresponding fall and rise of heart, kidney, and liver protein weight. These results were confirmed in experiments on fasted rats with the exception that under these conditions thyroidectomy did not appreciably decrease liver protein weight relatively to fasted controls. Increase in organ metabolism due to dinitrophenol had no effect on organ weight. 4. When experimental changes alter the composition of the body with respect to fat or water, the comparison of experimental and control organ weights in terms of any one function of body weight is fallacious. 5. Conditions that change kidney weight usually change liver protein weight in the same direction and roughly to the same degree. The possible meaning of two exceptions to this rule is discussed. 6. The observations made are regarded as supporting the hypothesis that, after weaning, change in the weight of the heart, kidney, and liver protein is determined mainly by change in the amount of work done by these organs.

Abstract: A non-antigenic mucoid polysaccharide similar to that described by Kendall, Heidelberger, and Dawson was isolated from group C hemolytic streptococci. A simple method for its quantitative estimation is described. By means of this quantitative method, as well as by the direct isolation of the carbohydrates, the size and persistence of capsules in young cultures of various strains have been related to the non-antigenic mucoid polysaccharide. Similarly, invasiveness in different strains has been related to the mucoid polysaccharide. Data indicating the non-haptene nature of this material are presented. An autolytic process, accelerated by bile, is involved in the loss of capsular material from young streptococci.

Abstract: 1. An artificial antigen containing the azobenzyl glycoside of cellobiuronic acid gives rise in rabbits to antibodies which: (a) give the Neufeld reaction and agglutinate Type III pneumococci, (b) confer passive protection on mice against infection with Types II, III, and VIII pneumococci. 2. Rabbits immunized with the artificial cellobiuronic acid antigen acquire active resistance to infection with virulent Type III pneumococci. 3. The antibodies evoked by an antigen containing the azobenzyl glycoside of cellobiose exhibit none of these phenomena.

Abstract: An acute, highly fatal epizootic disease of cats is described, which can be recognized by a fulminating and extreme leucopenia involving all types of white blood cells, aplasia of the bone marrow, including both the granulocytic and the erythrocytic series and occasionally the megakaryocytes, aplasia of lymphoid tissue, and characteristic intranuclear inclusion bodies in the cells of the intestinal mucosa and in certain cells of the spleen, lymph nodes and bone marrow. The infection has been induced in healthy cats by means of bacteria-free filtrates of emulsions of the spleen of infected animals. Collateral evidence supports the conclusion that the disease is due to a virus. The pathogenicity of the infectious agent has proved thus far to be strictly limited to the natural host.

Abstract: Experiments are described on the latency period in sensitization to poison ivy and on the time necessary for the agent to remain in contact with the skin. The chief matter of investigation concerned the manner in which the whole skin becomes sensitive following treatment at a particular site, and especially whether this is effected by way of the epidermis. Two methods were used to interrupt the continuity of the skin, one by cutting through both skin and the underlying thin muscular layer, the other by removing a strip of skin so as to spare the skin muscle. These procedures led to different results when poison ivy extract was applied to the areas thus isolated. In the first case, sensitization was mostly prevented, whereas with the second method generalized hypersensitiveness occurred almost uniformly. An explanation is to be found in the severance of the lymph vessels lying on the surface of the muscular layer, pointing to the necessity of a free lymph passage. On the other hand the experiments prove that general sensitization is not dependent upon maintaining the integrity of the skin around a treated area. An inhibition of sensitization by incisions extending through the panniculus carnosus was seen to some extent in anaphylactic sensitization with protein antigens, namely when sufficiently small amounts were employed.

Abstract: The venom of several species of poisonous snakes acts to spread India ink through the skin as do the spreading factors procurable from certain tissues and elaborated by invasive bacteria. The factor is most abundant in the venom of the Viperidae (rattlesnake) family and relatively scant in the venom of Colubridae proteroglypha (cobra) family, and it is absent from toad venom. Extracts of the supralabial glands of harmless snakes contain only negligible amounts of the factor. Rattlesnake venom heated at 65 degrees to 100 degrees loses a large proportion of its toxicity but retains the ability to spread ink. Rattlesnake venom that has lost its toxicity on standing or on heating markedly enhances the infection produced by bacterial or virus suspension in the rabbit skin. Antivenine serum inactivates both the toxic and spreading factors of venom.

Abstract: Vaccinia virus dropped into the nose of a susceptible animal does not appear in cervical lymph in less than 12 hours. After 12 hours, and thereafter continuously for 7 days, a stream of virus is entering the blood through the cervical lymph ducts. Virus passes through the lymph nodes. Virus is fixed by the lymphocytes, and the significance of this is discussed.

Abstract: 1. A substance extracted from group A hemolytic streptococcus is described, which induces active immunity in mice, and in rabbits gives rise to precipitins and to protective antibodies passively transferable to mice. 2. The active immunity in mice is principally type-specific, but some degree of non-type-specific immunity is also developed. The passively transferable protective antibodies are type-specific with only a slight suggestion of non-type specificity. In the precipitin test, the rabbit immune sera give both type-specific and non-type-specific reactions which have not been fully analyzed serologically. 3. Substances contained in the extract absorb the protective antibodies from the serum of rabbits immunized with whole hemolytic streptococci. 4. The most satisfactory method of extraction so far developed is fully described. Chemical tests on the material are consistent with the presence of protein and nucleic acid. 5. The type-specific M substance, prepared as previously described, was compared in some of its antigenic properties with the above mentioned substance. It was found capable of inducing active immunity in mice and of absorbing protective antibody from anti-bacterial immune serum in a manner qualitatively similar to that obtained with the preparations made by the newer methods.

Abstract: 1. When an emulsion containing virulent Treponema pallidum is added to serum from normal rabbits and from untreated immune syphilitic rabbits that have been infected with a homologous strain of T. pallidum the mixture incubated at 37°C., and injected intracutaneously into normal rabbits, typical syphilitic lesions commonly develop at the sites of inoculation of the normal serum-spirochete mixture, while at the sites of inoculation of immune serum-spirochete mixtures usually either no lesion develops or else the incubation period of the resulting lesions is shorter and the lesions remain smaller than those produced by normal serum-spirochete mixtures. 2. In a series of preliminary experiments, of 56 areas inoculated with serum-spirochete mixtures, in 42 the suppressive action of the syphilitic serum was manifest, in 10 areas questionable evidence of protection was noted, and in 4 areas there was no evidence that the syphilitic serum had exerted a suppressive or protective action. 3. The protective action of syphilitic serum seems to have been lessened by heating to 56°C. 4. The results of the protection test in three other series of experiments were as follows: ( a ) Of 12 areas in 6 rabbits inoculated with normal serum-spirochete mixtures typical syphilitic lesions developed, while in the same number of areas inoculated with immune serum-spirochete mixtures there was complete or partial suppression of lesions in all. ( b ) Of 45 areas inoculated with serum from 10 different immune syphilitic rabbits, definite evidence of protection was observed in 37, questionable evidence in 5, and no evidence of protection in 3. ( c ) Of 8 areas in 4 rabbits inoculated with immune serum-spirochete mixtures no lesions developed during the period of observation, while of 8 areas in the same rabbits inoculated with one of two normal serum-spirochete mixtures typical syphilitic lesions developed in each.

Abstract: 1. The fate of bacilli of reinfection at the portal of entry and in metastatic foci, and also the associated host responses, are essentially similar in rabbits and guinea pigs. 2. However, in the guinea pig tubercle bacilli of reinfection are more effectively fixed at the portal of entry than in the rabbit. 3. The guinea pig fixes at the site of reinfection unrelated substances, such as trypan blue and agar particles, more effectively than the rabbit. 4. At the site of a local non-specific inflammation precipitins from the circulating blood accumulate in higher concentration in tuberculous guinea pigs than in tuberculous rabbits. 5. These differing fixing capacities of the two species are associated with differences of extracellular character in the inflammation resulting from reinfection. (a) In the guinea pig, whose tissues are highly sensitized and greatly injured by the tubercle bacillus, the lymphatics adjoining the site of reinfection become thrombosed. In the rabbit whose tissues are moderately sensitized and less injured by the tubercle bacillus the corresponding lymphatics remain open. (b) In the guinea pig the fibrinous network at the site of inflammation forms a fine sieve-like structure. In the rabbit this network forms a coarse sieve-like barrier. 6. In rabbits and guinea pigs primarily infected, the destruction of tubercle bacilli takes place first and most extensively at the portal of entry. At this time they are less effectively destroyed in the nearest metastatic foci. Simultaneously they are still growing without hinderance in such foci in remote internal organs. 7. The cell-free body fluids of normal animals support the growth of tubercle bacilli in vivo. The body fluids of tuberculous animals under the same conditions are bacteriostatic for this microorganism. 8. Tubercle bacilli often multiply by preliminary subdivision into non-acid-fast granules, from which the acid-fast rods sprout. This confirms the work of Kahn.

Abstract: The escape of a vital dye from the lymphatics of the ears of living mice and its subsequent movement through normal and pathological connective tissue have been observed at high magnification. The dye first appears outside such channels as bristly, wavy lines of color, which can be bent and twisted by pressure with a micro probe and spring back to their original positions when the pressure is removed, as if the dye were fixed upon or between some tissue elements. Our findings indicate that this is the case, that the bristly lines of color are formed by dye moving between connective tissue fibers or along them. With the onset of mild edema, such as the dye induces secondarily, the bristles disappear, the coloration becoming diffuse and freely movable with the micro probe. When edema is induced before dye is introduced into the lymphatics, the character of its escape is wholly different. It first appears as a colored cloud, freely movable in the edema fluid, the manner of its passage into the tissues being completely changed. In the ears of mice partly dehydrated by bleeding, or in those of dead animals, the bristly or wavy lines were more evident than in normal individuals. It was plain that dehydration did not change the mode of transportation of the dye through the tissue but merely emphasized some of the characteristics of its passage. In animals injected intravenously with large amounts of physiological saline, with result in the presence of more tissue fluid than usual, the colored bristles were seldom seen. It is plain that connective tissue fibers serve indirectly as pathways for the transport of substances of large molecule. We have not been able by the dye method to demonstrate the presence of any free fluid in the normal tissues of the mouse ear.

Abstract: Tarring the ears of rabbits of one sort with a single kind of tar evoked epidermal tumors of a few sharply defined types, namely ordinary papillomas, carcinoids, carcinomas, and "frill horns." These last, relatively infrequent, are now recognized for the first time. The carcinoids have proved to be the expression of a spurious malignancy of papillomas, resulting from intercurrent influences, and they were wholly dependent upon these for their threatening aspect and behavior. Chief amongst such influences was continued tarring. It had the effect of establishing the papillomas, stimulated their proliferation, complicated their morphology, and rendered some of them disorderly, aggressive, and anaplastic. It brought all of the tissues of the ears into an excitable state, and often this state endured long after the skin had apparently returned to normal. The characters of the papilloma-carcinoids and of the frill horns were so different and distinctive as to imply the action of differing, specific causes. The papillomas were very like those induced with the Shope virus, and hence a point-to-point comparison was made of their manifestations, including the derivation of carcinomas from them. This comparison demonstrated that the unknown cause of the tar papillomas provoked neoplastic phenomena which were identical in all essential respects with those due to the virus. To suppose, for experimental purposes, that the papillomas which tarring elicits are caused by a virus rendered pathogenic by this procedure, is to demand least of the unknown. Yet it does not follow that they must be due to a virus.

Abstract: A method of estimating the purity of preparations of elementary bodies of vaccinia is described. It depends on the comparison of the number of infective units of virus in a given material with the number of elementary bodies. The latter figure is estimated from the dry weight of the preparation by means of a calculated value for the weight of a single dehydrated elementary body. Values for the ratio of infective units of vaccine virus to elementary bodies varied between 1 : 2.4 and 1 : 9.2 in seven consecutive experiments; the average was 1:4.2. These ratios indicate a high degree of purity of the preparation. Moreover, they indicate that a relatively high percentage of the elementary bodies in the preparations was infective.

Abstract: A series of deformities in the rabbit ranging from brachydactylia to acheiropodia have been described. Experimental breeding demonstrated that the occurrence of the deformities was determined by simple recessive hereditary factors and that the various types were genetically related and were not distinct hereditary entities. Embryological investigation showed the first abnormal change was a dilatation of blood vessels in affected buds. This was followed by hemorrhage and necrosis of the parts involved. Sloughing subsequently occurred, and the deformity was completely expressed by the 25th day of fetal life.

Abstract: Five strains of virus were recovered from nasal washings and feces. Four strains were of human origin, the fifth strain came from a monkey sacrificed at the height of the disease. Of the four human strains the first was isolated from the feces of a 14 year old child 7 days after the onset of illness. The second strain was from the nasal washings of a 6(1/2) year old child, 5 days after the onset of illness. The third and fourth strains were recovered from the same patient, a 2(1/2) year old child, 9 days after the onset of illness. One of these strains was obtained from nasopharyngeal washings and the other from the feces. The single monkey strain was isolated from the upper intestinal segment and appears to be the only instance of its isolation from this source in the literature. We believe that the detection of the virus in the nasal washings of two additional patients during convalescence lends further support to the belief that the virus of poliomyelitis is spread by human contact. Furthermore, the recovery of the virus from the gastro-intestinal tract with as great or greater frequency as from the upper respiratory tract, need not, it appears to us, alter our concept of the mode of entrance of the virus into the body, namely, by way of the upper respiratory tract. If the presence of the virus is conceded, then a consideration of the physiologic passage of nasal and oral secretions into the gastro-intestinal tract by reflex swallowing would serve to explain adequately the presence of the virus in those organs. It might even be further predicated that since the gastro-intestinal tract functions as a temporary reservoir for secretions from the upper respiratory tract, the gut should, after a time, contain the virus in higher concentration than any single sample of secretion obtained from the upper respiratory tract by nasal washing. It appears to us that failures to detect the virus in the gastro-intestinal tract are perhaps more indicative of inadequate procedures for its detection than of its absence. The recovery of the virus from the feces 7 and 9 days after the onset of illness takes on added significance. It indicates first, that the virus withstands the gastric acidity which under normal physiological conditions tends to keep gastric contents relatively free of bacteria. It further suggests that improper disposal of feces from patients with poliomyelitis may have serious public health consequences, particularly in smaller communities where inadequate sewage disposal may result in contamination of surrounding beaches or even local water systems.

Abstract: 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.