STUDIES UPON EXPERIMENTAL PNEUMONIA IN RABBITS : V. THE R?LE OF THE LEUCOCYTE IN EXPERIMENTAL PNEUMONIA. THE RELATION OF THE NUMBER OF ORGANISMS INJECTED TO THE MORTALITY.

1. The importance of the leucocyte in the resistance of animals to experimental pneumonia is emphasized by the fact that animals treated with benzol, a leucotoxic substance, rapidly succumb to the disease, while animals treated in like manner with toluol, a very similar chemical substance causing no leucopenia, show no decreased resistance. 2. The rôle of the leucocyte in the resistance of animals to experimental pneumonia is further emphasized by the fact that animals that respond to the pneumococcus infection with a leucocytosis, as occurs after the repeated injection of toluol, are more resistant to the pneumonia. Further, the hyperleucocytosis produced by repeated injection of nutrose before the production of pneumonia likewise seems to increase the resistance of the animals. 3. Experimental pneumonia is not necessarily fatal in rabbits. The factors determining the outcome of the disease are numerous; among these is the number of bacteria inoculated. Animals receiving small doses usually survive, while those receiving comparatively large numbers usually succumb.     

STUDIES ON THE MECHANISM OF RECOVERY IN PNEUMONIA DUE TO FRIEDL?NDER'S BACILLUS : I. THE PATHOGENESIS OF EXPERIMENTAL FRIEDL?NDER'S BACILLUS PNEUMONIA

Experimental pneumonia due to Friedländer''s bacillus was produced in white rats by the intrabronchial inoculation of the bacilli suspended in mucin. The pneumonia was lobar in type, was almost uniformly fatal, and simulated the acute form of the natural disease in human beings. The pathogenesis of the pneumonic lesion was studied by examination of microscopic sections of the lungs of animals killed at frequent intervals during the course of the infection. The histologic characteristics of the various stages of the pneumonia were essentially the same as those previously described in experimental pneumococcal (Type I) pneumonia except for the following differences: (1) In isolated areas of the lung in Friedländer''s pneumonia many more bacteria were encountered in the alveoli than were ever noted in experimental pneumococcal pneumonia. (2) Abscess formation was common in the late stages of Friedländer''s infection, whereas it was not noted in the pneumococcal lesion. (3) Organization of the alveolar exudate, rarely observed in experimental pneumococcal pneumonia, was a prominent feature of the pneumonia due to Friedländer''s bacillus. The mechanism of spread of Friedländer''s lesion appeared to be the same as that of pneumococcal pneumonia. Likewise there was noted the same phagocytosis of organisms in the lungs of even bacteremic animals dying of the infection.     

STUDIES ON EXPERIMENTAL PNEUMONIA : X. PATHOLOGY OF EXPERIMENTAL INFLUENZA AND OF BACILLUS INFLUENZ? PNEUMONIA IN MONKEYS.

1. Virulent influenza bacilli, when injected into the nose and throat of monkeys (Cebus capucinus and Macacus syrichtus), excite an acute inflammation of the upper respiratory tract, characterized by swelling and hyperemia of the mucous membrane, infiltration of the mucosa and subrnucosa with leucocytes, desquamation of epithelial cells, and the production of a mucopurulent exudate. The accessory sinuses are often implicated in the infection. 2. Experimental Bacillus influenzæ infections of the upper respiratory tract are frequently accompanied or followed by bronchiolitis, peribronchial infiltration, and bronchopneumonia with hemorrhage and edema in the early stage, emphysema and bronchiectasis in the later stages. In general, the process closely resembles uncomplicated Bacillus influenzæ pneumonia in man. 3. The injection of virulent influenza bacilli directly into the trachea of monkeys induces in them an experimental bronchiolitis and hemorrhagic bronchopneumonia, similar in all respects to spontaneous Bacillus influenzæ pneumonia. 4. In experimental Bacillus influenzæinfections of either the upper or lower respiratory tract the influenza bacillus can usually be recovered during .the acute stage by culture, either pure or in association with other bacteria. 5. In experimental Bacillus influenzæ infections in monkeys characteristic changes occur in the thymus gland—hyperplasia of the follicles, distention of the lymphatic channels, and infiltration of the parenchyma with leucocytes. This enlargement appears to be merely part of a general hyperplasia of the lymphoid structures in the cervical and thoracic regions.     

EXPERIMENTS ON THE R?LE OF LYMPHOID TISSUE IN THE RESISTANCE TO EXPERIMENTAL TUBERCULOSIS IN MICE

Mice either normal or splenectomized after exposure to X-ray are markedly more susceptible to bovine tuberculosis than are normal animals. Animals splenectomized a short time prior to inoculation are also more susceptible than normal, while those splenectomized eight to ten days before inoculation have about the same resistance as normal. The mice splenectomized three to four weeks before inoculation have a resistance increased over the normal, as has already been shown by Lewis and Margot. As X-ray in the doses used apparently affects only the lymphoid tissue and as the hypertrophy of the remaining lymphoid tissue after splenectomy is so rapid that the circulating lymphocytes may be much above the normal by the third week, it is concluded that this evidence, taken with the well known association of the lymphocytes with tuberculous lesions, points strongly to the lymphocyte as an important agent in the defensive mechanism against tuberculosis.     

EXPERIMENTS ON THE EPIDEMIOLOGY OF PSEUDORABIES : I. MODE OF TRANSMISSION OF THE DISEASE IN SWINE AND THEIR POSSIBLE R?LE IN ITS SPREAD TO CATTLE

Pseudorabies is a very fatal but non-contagious disease in cattle and the common laboratory animals. It is a relatively mild yet highly contagious disease in swine. It has been shown that in swine the nose serves both for the entrance and the exit of the virus. Furthermore, it has been observed that fatal pseudorabies infections in rabbits can be induced merely by bringing their abraded skin into contact with the noses of infected swine. The blood sera of swine on two farms where pseudorabies had occurred among the cattle were found to be capable of neutralizing pseudorabies virus. It is believed that in these instances the swine had a mild and unrecognized pseudorabies infection and transmitted their disease to the cattle with which they were associated, by transfer of the virus on their noses to the abraded skin of the cattle.     

EXPERIMENTS ON THE R?LE OF LYMPHOID TISSUE IN THE RESISTANCE TO EXPERIMENTAL TUBERCULOSIS IN MICE : III. EFFECT OF HEAT ON RESISTANCE TO TUBERCULOSIS.

Mice with high lymphocyte counts and increased activity of the lymphoid tissue induced by one exposure to intense dry heat exhibit a marked increase in the resistance to large doses of bovine tubercle bacilli as compared with that shown by control animals given a similar inoculation. This resistance, judged by the time of survival after inoculation, is increased from two- to threefold. The average length of life after inoculation for three groups of heated mice was 88, 69, and 67 days respectively, while the control groups averaged 16, 29, and 28 days respectively.     

THE R?LE OF THE THEBESIAN VESSELS IN THE CIRCULATION OF THE HEART

In summary, evidence has been presented to show a direct connection other than through the capillaries between the coronary arteries and the chambers of the heart. This connection was shown by perfusion, injections and serial sections to be through the Thebesian veins. Communications between the larger coronary veins and the Thebesian veins were also demonstrated by the same methods. Serial sections through Thebesian veins have shown capillaries draining directly into them. Under certain conditions it has been shown that as much as 90 per cent of the arterial flow may escape via the Thebesian vessels. Lastly, in the event of gradual closure of the orifices of the coronary arteries, the Thebesian vessels can supply the heart muscle with sufficient blood to enable it to maintain an efficient circulation.     

EXPERIMENTS ON THE R?LE OF LYMPHOID TISSUE IN THE RESISTANCE TO EXPERIMENTAL TUBERCULOSIS IN MICE : II. EFFECT OF CANCER IMMUNITY ON RESISTANCE TO TUBERCULOSIS.

Mice so x-rayed as greatly to reduce the lymphoid tissue are rendered highly susceptible to tuberculous infection. On the other hand) when a marked lymphocytosis is induced by first immunizing mice against, and then inoculating them with cancer, the resistance to tuberculous infection is greatly enhanced. This heightened resistance may be set aside and even changed to a state of increased susceptibility to the infection by again depleting the lymphocytes by means of the x-ray.     

THE FREQUENCY OF BACILLUS INFLUENZ? IN THE NOSE AND THROAT IN ACUTE LOBAR PNEUMONIA

1. Bacillus influenza is frequently found in association with lobar pneumonia. 2. In lobar pneumonia both Bacillus influenza and pneumococcus are frequently found in the nose. 3. The influenza bacilli found in the upper respiratory tract of cases of lobar pneumonia are of various types. 4. The exact significance of these findings is at the present time not clear.     

STUDIES ON THE MECHANISM OF RECOVERY IN PNEUMONIA DUE TO FRIEDL?DER'S BACILLUS : III. THE R?LE OF "SURFACE PHAGOCYTOSIS" IN THE DESTRUCTION OF THE MICROORGANISMS IN THE LUNG

Phagocytosis of encapsulated Friedländer''s bacilli has been demonstrated in the lungs of rats in the absence of both circulating and local antibody. The mechanism of phagocytosis independent of antibody has been shown to be due to the same surface factors that operate in the phagocytosis of Type I pneumococcus under similar conditions. Direct observation of the phagocytic process reveals that leucocytes in the lung can phagocyte unopsonized Friedländer''s bacilli only by trapping them against the surfaces of alveolar walls or bronchi, or by pinning them against the surfaces of adjacent leucocytes. Evidence is presented that Friedländer''s bacilli thus phagocyted are rapidly killed in the cytoplasm of the phagocytic cells. Reasons are discussed for the failure of prolonged chemotherapy to cure lung abscesses that not infrequently complicate the pneumonia due to Friedländer''s bacillus.     

INFECTIOUS CATARRH OF THE ALBINO RAT : I. EXPERIMENTAL TRANSMISSION IN RELATION TO THE R?LE OF ACTINOBACILLUS MURIS

A disease syndrome referred to as infectious catarrh, encountered under natural conditions of exposure in a rat colony, was transmitted to selected animals and maintained for 5 years by nasal instillation or contact. During this period 37 passages were made in 156 rats, the rates of pneumonia, otitis media, and rhinitis being 28, 63, and 87 per cent, respectively. After the 12th passage, Brucella bronchiseptica and Actinobacillus muris (B. actinoides var. muris), which were originally present, were no longer cultivable from infected rats. By reason of the maintenance of infectious catarrh in the absence of the latter and also because of its non-invasiveness on nasal instillation, it is now believed that Actinobacillus muris is of no direct etiological significance.     

THE R?LE OF THE THYROID IN THE REGULATION OF THE BLOOD CHOLESTEROL OF RABBITS

1. The blood cholesterol of rabbits on a normal diet without added cholesterol is increased only slightly (19 per cent) by thyroidectomy. 2. In rabbits with a hypercholesterolemia due to long continued cholesterol feeding, thyroidectomy causes a marked rise (137 per cent) in the blood cholesterol. This rise is usually maintained. 3. When long continued cholesterol feeding has failed to cause a rise in the blood cholesterol of rabbits, thyroidectomy abolishes this resistance and a hypercholesterolemia is promptly produced. 4. A single injection of thyroxin causes a significant drop in the blood cholesterol of rabbits with hypercholesterolemia. This reaction is not influenced by thyroidectomy. 5. Potassium iodide causes an increase in the blood cholesterol of rabbits with hypercholesterolemia. This reaction is not influenced by thyroidectomy in contrast to the effect of KI in preventing a rise in blood cholesterol when given concurrently from the beginning of cholesterol feeding, an effect which is abolished by thyroidectomy. It is suggested that two different mechanisms are involved. 6. A single injection of insulin produces a fall in the blood cholesterol of rabbits with hypercholesterolemia. If anything, thyroidectomy increases the magnitude of this effect.     

STUDIES ON THE MECHANISM OF RECOVERY IN PNEUMONIA DUE TO FRIEDL?NDER'S BACILLUS : II. THE EFFECT OF SULFONAMIDE CHEMOTHERAPY UPON THE PULMONARY LESION OF EXPERIMENTAL FRIEDL?NDER'S BACILLUS PNEUMONIA

Sulfonamide chemotherapy was found to cure rats of an otherwise fatal form of experimental Friedländer''s bacillus pneumonia when treatment was begun 6 hours after inoculation. Most of the pneumonic lesions cleared completely, but an occasional animal exhibited small residual abscesses in the previously consolidated lung. The recovery process taking place in the lungs was studied histologically at various intervals during therapy. As in the case of pneumococcal pneumonia, the principal action of the sulfonamide was upon the bacteria in the advancing edema zone at the periphery of the pneumonic lesion. The bacteriostatic action of the drug appeared to stop the spread of the pneumonia, and the Friedländer bacilli were ultimately ingested and destroyed by the phagocytic cells in the alveolar exudate. The phagocytosis of bacteria in the lung was shown to be unrelated to the presence of antibody in the blood.     

THE R?LE OF THE RETICULO-ENDOTHELIAL SYSTEM IN IMMUNITY : VI. THE EFFECT OF ENDOTHELIAL BLOCKADE ON THE STORAGE AND DISTRIBUTION OF NEOARSPHENAMINE

1. Blockade of the reticulo-endothelial system by means of a single injection of India ink caused a marked retention of neoarsphenamine in the blood of guinea pigs during the first twenty minutes of observation after intravenous injection, as contrasted with the rapid disappearance of the drug from the blood of normal controls. 2. Rabbits blocked by a single dose of India ink showed a slower elimination of the drug from the circulation following the first few hours after intravenous injection than corresponding controls. 3. The arsenic content of the liver of mice, which received neoarsphenamine intravenously after a preceding blocking injection with India ink, was appreciably lower than the arsenic content of the normal organ under similar experimental conditions.     

A STUDY OF THE CHANGES IN THE BLOOD AND BLOOD-FORMING ORGANS PRODUCED BY CYTOTOXIC SERA,WITH SPECIAL REFERENCE TO H?MOLYMPHOTOXIN

(1) The cytotoxins are not specific. (2) The changes occurring after the injection of different cytotoxins are similar and do not vary in kind. (3) The changes do, however, vary in degree in the following order, the one having the most marked effect being placed first, etc.: (a) Hæmolymphotoxin, (b) Splenotoxin, (c) Lymphotoxin, (d) Endotheliotoxin, (e) Nephrotoxin, (f) Hepatotoxin. (4) Nephrotoxin causes the most specific change. (5) The hæmolymph glands play some important part in the production of eosinophiles. The hæmolytic action of hæmolymphotoxic serum is greater than that of other cytotoxic sera. (6) The histological changes which are observed in every case are secondary to the hæmolytic factor present in all cytotoxic sera.     

ON THE APPEARANCE OF CERTAIN AM?BOID BODIES IN THE BLOOD OF VACCINATED MONKEYS (RHOESUS) AND CHILDREN,AND IN THE BLOOD FROM CASES OF VARIOLA : AN EXPERIMENTAL STUDY.

1. The claim of L. Pfeiffer that small granular amœboid bodies are present in the blood of vaccinated children and calves, and in the blood from cases of variola, during the stage of fever is confirmed. A nucleus has not been positively made out in any of these bodies. 2. Granular amœboid bodies, having a diameter about one-third that of a red blood cell, appear, also, in the blood of the monkey during the active stage of vaccinia and disappear with the decline of the local inflammation. 3. A body of like appearance, granulation and size may occasionally be found in the normal blood of monkeys and children. 4. Pale amœboid bodies, containing a few dark pigment-like granules, are present in the blood from cases of variola and in the blood of the variolated monkey. Bodies of like appearance may occasionally be found in the blood of vaccinated children and monkeys.