bluuebunny/crossref_metadata_2025 huggingface dataset:
PULMONARY HYPERTENSION IN RATS LIVING UNDER COMPRESSED AIR CONDITIONS
Authors: Bennett Granville A. , Smith F. J. C.
Published: June 2004

1. Pulmonary arterial hypertension was demonstrated in a series of rats that had been kept for 24–31 days in an environment of compressed air, having a barometric pressure of 3040 mm. Hg. The partial pressure of oxygen was 635 mm. Hg, which is equivalent to an 83.6 per cent oxygen mixture at normal barometric pressure.

2. Sclerosing changes in the pulmonary arterioles have been observed which precede the development of demonstrable hypertension in the pulmonary circulation. These vessels showed histological changes that were indicative of injury after 3 days of exposure. There was a thickening of the walls which stained more intensely with eosin, as well as marked perivascular edema and often a narrowing of the lumina. Progressive thickening, narrowing, and hyalinization of the pulmonary arterioles occurred later, after the disappearance of perivascular edema. These changes appeared very similar to the renal arterial lesions seen at autopsy in patients dying from malignant hypertension.

3. Pathological examination did not reveal significant or constant changes from normal in any organs except the lungs and heart. The blood vessels of the systemic circulation showed no pathological change.

4. The walls of the large pulmonary arteries increased in thickness rapidly after the 3rd day of exposure. This change was due to the progressive formation and condensation of fibrous tissue outside of the media and to a lesser extent to thickening of the alternate layers of elastic tissue and smooth muscle in the arterial wall.

5. Marked dilatation of the right ventricle and conus arteriosus as well as small areas of scar tissue formation in the right ventricle were present on prolonged exposure. A few hearts showed larger areas of fibrosis that were visible on macroscopic examination.

6. The systemic arterial blood pressure of a small series of rats exposed to compressed air for 38 days and examined 7 to 10 days after decompression was in each instance less than one-half the average normal pressure.

7. The findings in this study are consistent with the clinical and pathological signs of pulmonary hypertension in man.

8. The anatomical alterations observed in the alveolar units of the lungs were essentially the same as those previously described (1).

9. A method has been devised whereby pulmonary arterial hypertension, accompanied by important sclerotic changes in the arteries of the pulmonary circulation can be induced for investigation.
BLOOD PLASMA PROTEIN REGENERATION CONTROLLED BY DIET
Authors: Holman Russell L. , Mahoney Earle B. , Whipple George H.
Published: June 2004

When blood plasma proteins are depleted by bleeding and return of the washed red cells (plasmapheresis) the regeneration of new plasma proteins can be controlled at will by diet. The amount and character of protein intake is all important.

Liver protein and casein are efficient proteins to promote rapid regeneration of plasma proteins but some vegetable proteins are also efficient.

The blood plasma proteins are reduced by plasmapheresis close to the edema level (3.5–4.0 per cent) and kept at this level by suitable exchanges almost daily. The amount of plasma protein removed is credited to the given diet period.

A basal ration is used which is poor in vegetable protein (potato) and contains no animal protein. The dog on this ration can be kept in nitrogen balance but can produce only about 2 gm. plasma protein per kilo body weight per week. With liver or casein feeding this production can be increased three- or fourfold.

A reserve of protein building material can be demonstrated in the normal dog when its plasma proteins are depleted. In the first 3 weeks of depletion this reserve in excess of the final basal output may amount to 3–20 gm. protein. This may be stored at least in part in the liver. As much as 50 per cent of this reserve may be albumin or albumin producing material.

A reversal of the albumin-globulin ratio may be observed on the basal diet alone. The reversal will always follow plasmapheresis with the dog on the basal diet and the total plasma protein output will consist approximately of 2 parts globulin and 1 part albumin. Liver diet will raise the production and output of albumin and bring the ratio back toward normal. Albumin production may actually exceed the globulin output during liver diet periods. The change is less conspicuous with casein but in the same direction.
PERIVASCULAR REACTIONS IN LUNG AND LIVER FOLLOWING INTRAVENOUS INJECTION OF STREPTOCOCCI INTO PREVIOUSLY SENSITIZED ANIMALS
Authors: Hitchcock Charles H. , Camero Anthony R. , Swift Homer F.
Published: June 2004

Intravenous inoculation of small doses of non-hemolytic streptococci into previously sensitized rabbits is usually followed by the appearance of perivascular cellular aggregates in lung and liver.

The characteristic cell in these aggregates is moderately large, with vesicular nucleus, prominent nucleoli, clumped chromatin, and basophilic cytoplasm. In addition, the lesions contain small lymphocytes and granulocytes.

This lesion is easily differentiated by architecture and cell content from normally occurring lymphoid aggregates, and from spontaneous rabbit hepatic cirrhosis.

This mononuclear response does not occur when the intravenous dose is large enough to cause death of the animal within 24 hours.

In spleen and lymph nodes the characteristic basophilic cells, which normally occur in these organs, are present in increased numbers.

Following intravenous treatment alone, or sensitization without intravenous treatment, the lesions occur much less frequently, and when present are smaller and more sparsely found.

Inasmuch as in the present series of experiments this lesion was not found in normal animals, and infrequently in those treated by the intravenous route alone, it is suggested that the preliminary sensitization serves to enhance the animal's reactivity to the antigen. In this way a small dose of bacteria is capable of eliciting the cellular phenomenon, which in unsensitized animals appears only when larger doses of antigen are administered over longer periods of time. Too large a dose of antigen, however, results in shock and cell death rather than proliferation.
SINGLE CELL INOCULATIONS WITH TREPONEMA PALLIDUM
Authors: Thomas Clarence S. , Morgan Hugh J.
Published: June 2004

The injection of one or several Treponema pallidum into the testicles of rabbits does not induce syphilitic infection.

A negative tissue transfer experiment does not preclude the presence of Treponema pallidum in the inoculum nor does it indicate the absence of syphilis in the source animal.
THE VITAMIN B1 AND B2 G CONTENT OF LIVER EXTRACT AND BREWERS' YEAST CONCENTRATE
Authors: Miller D. K. , Rhoads C. P.
Published: June 2004

1. Liver extract powder, No. 343 Lilly, and the same material prepared for parenteral use, when administered daily by mouth in amounts derived from 2.5 gm. of fresh whole liver, to rats weighing from 40 to 50 gm., contain sufficient vitamin B1 to support normal growth, provided the animals receive in addition an adequate amount of vitamin B2 G. Moreover, liver extract in the forms mentioned, administered in the same amounts, does not contain sufficient vitamin B2 G to maintain normal growth of similar rate when all other necessary constituents of the diet are provided.

2. Liver extract (Lilly) in the form prepared for parenteral use, when administered daily by intraperitoneal injections, in amounts derived from 2.5 gm. of fresh whole liver, to rats under standard experimental conditions, does not contain sufficient vitamin B2 G to maintain normal growth. Furthermore, the amount of vitamin B1 present in liver extract in this form is not as effective in supporting normal growth when given by intraperitoneal injection as it is when given by mouth.

3. Vegex, when administered daily in amounts of 50, 150, and 250 mg. to rats of 40 to 50 gm. in weight contains sufficient vitamin B1 to maintain normal growth of the rats, provided the animals receive in addition an adequate amount of vitamin B2 G. However, vegex in the same amounts does not contain sufficient vitamin B2 G to support normal growth of similar rats when all other necessary constituents of the diet are provided.

4. These experiments indicate that the extrinsic, anti-anemic factor of Castle and the thermostable growth-promoting food constituent, commonly known as vitamin B2 G, are not identical.
STUDIES ON EXPERIMENTAL HYPERTENSION
Authors: Goldblatt Harry , Lynch James , Hanzal Ramon F. , Summerville Ward W.
Published: June 2004

These experiments indicate that, in dogs at least, ischemia localized to the kidneys is a sufficient condition for the production of persistently elevated systolic blood pressure. When the constriction of both main renal arteries is made only moderately severe in the beginning, the elevation of systolic blood pressure is unaccompanied by signs of materially decreased renal function. In this respect the hypertension in these animals resembles the hypertension which is associated with so called benign nephrosclerosis in man. Subsequent increase of the constriction of the main renal arteries does not materially damage renal function, probably because of adequate development of accessory circulation. More delicate methods for detecting a change may yet prove that some damage does occur. Almost complete constriction of both main renal arteries, from the beginning, results in great elevation of systolic blood pressure which is accompanied by severe disturbance of renal function and uremia. This resembles the type of hypertension which is associated with so called malignant nephrosclerosis, in the sense of Fahr (17). In several of the animals with persistent elevation of systolic blood pressure, anatomical changes were observed in the glomeruli, vessels and parenchyma of the kidneys which are most probably directly referable to the ischemia.

It is hoped that these investigations will afford a means of studying the pathogenesis of hypertension that is associated with renal vascular disease.
THE FILTERING CAPACITY OF LYMPH NODES
Authors: Drinker Cecil K. , Field Madeleine E. , Ward Hugh K.
Published: June 2004

In anesthetized dogs the popliteal lymph node alone, and the popliteal and iliac lymph nodes in series, have been perfused with solutions containing dog erythrocytes and streptococci. The perfusions have been carried out under conditions of lymph flow and pressure within the limits of those occurring in the actively moving dog, or after a severe degree of inflammatory swelling has developed. Figures for filtration are given, with protocols of typical experiments. They indicate that normal lymph nodes possess a high degree of filtering efficiency—an efficiency so great as to make it fairly certain that in a part kept at rest early in an infection, practically no microorganisms would escape the nodes in the line of drainage.
I. CHOLESTEROL AND CHOLESTEROL ESTERS IN DOG BILE
Authors: Wright Angus
Published: June 2004

The colorimetric method for the determination of total cholesterol in dog bile is consistently accurate as checked by the oxidative digitonin method. This method has the further advantages of being simple, rapid and economical.

A method for the determination of esterified cholesterol in bile is described and it is shown that there are no esters of cholesterol in normal dog bile.
II. BILE CHOLESTEROL
Authors: Wright Angus , Whipple George H.
Published: June 2004

Under uniform diet conditions the normal bile fistula dog will eliminate pretty constant amounts of cholesterol—about 0.5 to 1.0 mg. cholesterol per kilo per 24 hours.

Diets rich in cholesterol (egg yolk) will raise the cholesterol output in the bile but compared to the diet intake (1.5 gm. cholesterol) the output increase in the bile is trivial (5–15 mg.). Calves' brains in the diet are inert.

Bile salt alone will raise the cholesterol output in the bile as much and often more than a cholesterol rich diet.

Bile salt plus egg yolk plus whole bile give maximal output figures for bile cholesterol—60 mg. per 24 hours.

Liver injury (chloroform) decreases both bile salt and cholesterol elimination in the bile.

Blood destruction (hydrazine) fails to increase the bile cholesterol output and this eliminates the red cell stroma as an important contributing factor.

Certain cholagogues (isatin and decholin) will increase the bile flow but cause no change in cholesterol elimination.

The ratio of cholesterol to bile salt in the bile normally is about 1 to 100 but the bile salts are more labile in their fluctuations.

The ratio is about reversed in the circulating blood plasma where the cholesterol is high (150–300 mg. per cent) and the bile salt concentration very low.

Cholesterol runs so closely parallel to bile salt in the bile that one may feel confident of a physical relationship. In addition there is a suspicion that the bile cholesterol is in some obscure fashion linked with the physiological activity of hepatic epithelium.
III. BLOOD PLASMA CHOLESTEROL
Authors: Hawkins William B. , Wright Angus
Published: June 2004

Hypocholesteremia with dissociation of the normal ratio of esterified to total cholesterol is related to chronic liver injury caused by chloroform.

Hypercholesteremia may develop after prolonged biliary obstruction.

The hypercholesteremia of chronic biliary obstruction may be promptly reduced below normal by chloroform poisoning or bile duct infection.

Acute injury of liver due to chloroform anesthesia may cause no change in blood plasma cholesterol.

Absence of bile in the intestine with faulty fat absorption does not cause the development of hypocholesteremia with dissociation of the ester ratio.

Poor food consumption or short periods of fasting may cause no change in blood plasma cholesterol.

Liver cells injured by chloroform may subsequently become resistant to chloroform.

After prolonged biliary obstruction, the liver is apparently more sensitive to small doses of chloroform by mouth.

Analysis of blood plasma cholesterol may have a clinical application in differentiation between simple obstructive and parenchymatous lesions of the liver.
STUDIES ON TYPHUS FEVER
Authors: Zinsser Hans , Castaneda M. Ruiz
Published: June 2004

Under uniform diet conditions the normal bile fistula dog will eliminate pretty constant amounts of cholesterol—about 0.5 to 1.0 mg. cholesterol per kilo per 24 hours.

Diets rich in cholesterol (egg yolk) will raise the cholesterol output in the bile but compared to the diet intake (1.5 gm. cholesterol) the output increase in the bile is trivial (5–15 mg.). Calves' brains in the diet are inert.

Bile salt alone will raise the cholesterol output in the bile as much and often more than a cholesterol rich diet.

Bile salt plus egg yolk plus whole bile give maximal output figures for bile cholesterol—60 mg. per 24 hours.

Liver injury (chloroform) decreases both bile salt and cholesterol elimination in the bile.

Blood destruction (hydrazine) fails to increase the bile cholesterol output and this eliminates the red cell stroma as an important contributing factor.

Certain cholagogues (isatin and decholin) will increase the bile flow but cause no change in cholesterol elimination.

The ratio of cholesterol to bile salt in the bile normally is about 1 to 100 but the bile salts are more labile in their fluctuations.

The ratio is about reversed in the circulating blood plasma where the cholesterol is high (150–300 mg. per cent) and the bile salt concentration very low.

Cholesterol runs so closely parallel to bile salt in the bile that one may feel confident of a physical relationship. In addition there is a suspicion that the bile cholesterol is in some obscure fashion linked with the physiological activity of hepatic epithelium.
SELECTION WITH THE MAGNET AND CULTIVATION OF RETICULO-ENDOTHELIAL CELLS (KUPFFER CELLS)
Authors: Rous Peyton , Beard J. W.
Published: June 2004

Methods and apparatus are described where with living Kupffer cells can be procured from the liver of the rabbit and the dog for study and cultivation in vitro. Almost none of these cells can be dislodged from the normal liver by forcible perfusion; but after they have taken up finely particulate matter (India ink, iron oxide), they come away in great numbers. When they have phagocyted ferromagnetic iron oxide they can be selected with a magnet from amongst the blood elements present in suspension with them; and they are obtainable in quantity by this means. They do poorly when plated in a thin plasma clot, failing to multiply or to assume their characteristic shape; but they flourish when allowed to attach themselves to strands of lens paper bathed in serum that is frequently changed.

Bacterial infection of serum cultures of Kupffer cells from normal rabbits and dogs occurs only as the result of secondary contamination of the materials, whereas it regularly develops in cultures from animals with fever induced by the injection of nucleic acid or of killed B. prodigiosus. Kupffer cells obtained under such conditions are abnormally active, and some can be washed out of the liver of sick animals in the absence of any preliminary phagocytosis of particulate matter. The facts have a bearing both on the conditions conducing to blood invasion and on the response of the Kupffer cells in the emergency.

The characters of the isolated Kupffer cells and the results of tests of their presumptive functions will be described in later papers.
EXPERIMENTAL TYPE III PNEUMOCOCCUS PNEUMONIA IN MONKEYS
Authors: Francis Thomas , Terrell Edward E.
Published: June 2004

It has been possible by the intratracheal or intrabronchial inoculation of Type III Pneumococcus to produce in monkeys of the M. cynomolgos species an experimental pneumonia which in its clinical aspects closely resembles pneumococcus lobar pneumonia in man. The experimental disease is characterized by the development of a well localized pulmonary lesion of lobar distribution which tends to spread, the frequent occurrence of septicemia, a sustained fever, and the termination of the infection after a variable interval, in recovery or death of the animal. Wide variations in the severity of the disease in different monkeys have been noted. These variations appear to be due primarily to differences in the resistance of individual animals. The height of the septicemia accompanying the experimental pneumonia has been found to be the most valuable objective index of the probable outcome of the disease. Other factors which may influence the course and outcome of the disease are discussed.
LOUPING ILL IN MAN
Authors: Rivers Thomas M. , Schwentker Francis F.
Published: June 2004

Four instances of infection in man which are believed, because of the circumstances under which they occurred and in view of the results of neutralization tests, to represent cases of louping ill have been described. Evidence obtained by the neutralization tests is in favor of the idea that the antibodies against louping ill virus demonstrated in certain sera were most likely the result either of contact with or of infection with the active agent.
THE EFFECT OF A GROWTH-PROMOTING EXTRACT OF THE ANTERIOR PITUITARY ON THE EARLY GROWTH OF THE ALBINO RAT
Authors: Targow A. M.
Published: June 2004

Castrate male albino rats were injected with a growth-promoting extract of bovine anterior pituitary from the 21st day of life (day of castration) to the 56th day (average for group) at which time the difference in weight between the pituitary-injected animals and controls was first clearly discernible. In comparison to controls the pituitary-injected animals at this stage showed: (1) a decrease in the weight of the pituitary gland; (2) an increase in nose-anus length; (3) an increase in the weight of heart, lungs, liver, and kidneys which is shown to be of the nature of a splanchnomegaly; (4) an increase in the weight of the blood removed; (5) an increase in the water content of the skin and the kidneys; (6) a tendency toward an increase in weight of the carcass. The significance of these findings is discussed.
STUDIES ON PSEUDORABIES (INFECTIOUS BULBAR PARALYSIS, MAD ITCH)
Authors: Hurst E. Weston
Published: June 2004

After intramuscular, intradermal and subcutaneous inoculation, the pseudorabies virus reaches the central nervous system by way of the peripheral nerves, although it is circulating in the blood. Centrifugal spread from the infected nervous tissues by the neural route also occurs. After intracerebral inoculation the virus passes in the reverse direction, down the nervous axis. The Aujeszky strain invades the blood stream more readily than does the Iowa strain; but possibly with repeated passage the latter is approximating in this respect more closely the classical Aujeszky strain. After intravenous inoculation, effective with even small doses, virus is rapidly removed from the blood, and multiple infective foci are established in various organs; thence ascent of the virus by the peripheral nerves leads to infection of the central nervous system, the symptomatology differing according to whether the spinal cord or the medulla is first reached. The lack of evidence that the virus can penetrate directly the hemato-encephalic barrier deserves emphasis. When subcutaneous inoculation is practised in an area deprived of its nerve supply, the ability of the virus to invade the blood stream permits it to establish infective foci in the various viscera, and, after a predictable delay, the course of infection resembles that following intravenous injection. The pseudorabies virus is pantropic; i.e., it readily attacks cells derived from any embryonic layer. Lesions in the adrenal gland following intravenous inoculation are very like those due to herpes virus similarly introduced, this being one point of similarity in the pathogenic action of the two organisms. The relation of the pseudorabies virus to other viruses affecting the central nervous system is discussed.
SEROLOGICAL STUDIES ON AZOPROTEINS
Authors: Landsteiner E. , van der Scheer J.
Published: June 2004

A study was made of the specificity of artificial compound-antigens containing aliphatic chains.

Striking specificity was exhibited in the reactions of compounds with short chains containing a carboxyl group; for instance succinic acid could be differentiated from malonic or glutaric acid which contain one fewer and one more carbon atom respectively. With the substances containing longer chains, reactions were observed which, although specific to a certain extent, appear to depend mainly on the general physicochemical properties of long aliphatic chains.

With a limited number of substances the influence of substituents —halogen, OH, NH2—on the serological specificity was investigated.

By means of inhibition reactions it was possible to demonstrate the serological specificity of cis-trans isomers such as maleic and fumaric acid.
THE PRODUCTION OF STREPTOCOCCUS HEMOLYTICUS BACTEREMIA IN NON-SPECIFICALLY SENSITIZED ANIMALS
Authors: Burn Caspar G. , Chandler Caroline A. , Hartshorn Mildred
Published: June 2004

Rabbits sensitized to horse serum developed a bacteremia of 9 to 12 hours' duration when they were inoculated simultaneously with normal horse serum and a strain of Streptococcus hemolyticus, while the bacteria could only be isolated from the blood stream of non-sensitized animals within the first 3 hours after inoculation. On the other hand, when antisera are employed as the antigen for shocking the sensitized rabbits, there is a significant increase in the number of bacteria in the blood stream in contrast to the control animals, but there is no evidence of a prolongation of the bacteremia.
STUDIES ON HOST FACTORS IN PNEUMOCOCCUS INFECTIONS
Authors: Goodner Kenneth
Published: June 2004

The power of specific antipneumococcus serum to protect rabbits against infection with Type I Pneumococcus has been studied with reference to the capacity of the animal to utilize the specific antibodies. Under conditions ensuring relatively controlled genetic factors it was found that heavier animals and those with high white blood cell counts are much better able to utilize the passively conferred immune principles. The interrelationships of the extrinsic and intrinsic factors responsible for immunity have been discussed.
STUDIES ON HOST FACTORS IN PNEUMOCOCCUS INFECTIONS
Authors: Goodner Kenneth
Published: June 2004

In the experimental disease brought about by infecting rabbits intradermally with Type I Pneumococcus the use of relatively small or subeffective amounts of specific antipneumococcus serum leads to the survival of some individuals and the death of others. It has been shown that both the severity of the infection and the white blood cell count are factors in the determination of the outcome of the disease but that there remain other host factors which have to do with the utilization or functioning of the specific antisera.
RESULTS OF IRRADIATING STAPHYLOCOCCUS AUREUS BACTERIOPHAGE WITH MONOCHROMATIC ULTRAVIOLET LIGHT
Authors: Gates Frederick L.
Published: June 2004

The incident energies required to kill Staphylococcus aureus or to inactivate its homologous bacteriophage have been measured at the various wave-lengths of the quartz mercury vapor arc between 238 and 302 mµ and found to run strictly parallel, the readings for the S. aureus phage being obtained at a uniformly higher energy level. This difference in levels is of less significance than the striking similarity in the shapes of the energy curves, which indicate that in both instances the same organic structures are absorbing the radiations. The results are open to three interpretations. The most obvious is that the bacteriophage is a submicroscopic organism. Again, it is possible that the bacteriophage is a product of its own lytic action on the homologous bacterium and contains the essential structural units which in S. aureus also are destroyed by ultraviolet light and thus cause the death of the organism. A third, more remote explanation is that the phage, of wholly unknown nature, is absorbed on S. aureus material in so intimate a bond that the alteration of this material by irradiation renders the phage incapable of further lytic activity.
FATE OF BILIRUBIN IN THE SMALL INTESTINE
Authors: Sackey M. S. , Johnston C. G. , Ravdin I. S.
Published: June 2004

Since there was no loss of bilirubin from the jejunal loop, and no loss of bilirubin when pigment was incubated with juice from the loop segment, or juice from the entire small intestine, it may be concluded that the intestinal juice per se has no effect in converting bilirubin to urobilin in a 2 hour period, and that in the jejunal loop there was no absorption of pigment or no conversion to urobilin. The experiments showing loss of pigment in the entire intestinal tract suggest that in some place other than the jejunal portion of the intestine the combined activity of intestinal contents and intestinal cells does affect the bilirubin in the intestine. Whether the loss of bile pigment under such circumstances is due entirely to conversion, or to conversion and absorption, or to absorption of bilirubin as such, remains to be answered by subsequent investigations.
TRANSPLANTATION OF TOOTH GERM ELEMENTS AND THE EXPERIMENTAL HETEROTOPIC FORMATION OF DENTIN AND ENAMEL
Authors: Huggins C. B. , McCarroll H. R. , Dahlberg A. A.
Published: June 2004

The formation of dentin and enamel in the abdominal wall in young pups was achieved by transplantation of the soft tissues of the developing tooth germ. An interesting finding was the cytomorphosis of the epithelium of the enamel organ. When this was transplanted so that the ameloblasts were in contact with the odontoblasts the cylindrical character of the epithelial cells was preserved and enamel was produced; otherwise the cylindrical shape of these cells was lost and a stratified epithelium resulted, resembling the gingival and certain tumors (the adamantinoma) of the jaw and related structures. This degenerated epithelium did not produce enamel and had an important characteristic of not forming cysts in a closed connective tissue space, instead forming islands and cords of cells with epithelial pearl formation. Thus the influence of mesodermic connective tissue derivatives on the form and function of epithelium is presented. The odonto-blasts were found capable of survival as such and readily formed new dentin in transplantation; the stellate cells of the pulp were inert from the standpoint of inducing calcification.
THE EFFECT OF ANTECEDENT INFECTION AND IMMUNIZATION WITH STREPTOCOCCI UPON THE REACTIVITY OF RABBITS TO HORSE SERUM
Authors: Schultz Mark P. , Swift Homer F.
Published: June 2004

1. The cutaneous responses of rabbits to small doses of horse serum intracutaneously is described. After an original injection of 0.1 cc. a secondary reaction often occurs about the 9th day, and tests at 3 day intervals with 0.001 cc. quantities indicate that general skin hypersensitivity is established at this time. Circulating precipitins for horse serum appear later. As the degree of sensitivity increases, lesions resulting from test doses reach a maximum development more quickly.

2. The reactivity of rabbits to horse serum is greatly increased by antecedent sensitization of the animals with repeated small intracutaneous inoculation of indifferent streptococci or immunization with large intravenous injections of either indifferent or hemolytic streptococci. Doses of indifferent streptococci precisely comparable to those producing greatly enhanced reactivity when given intracutaneously, increase reactivity to horse serum irregularly and to slight degree when injected intravenously.

3. Increases in reactivity (allergic irritability) are made evident by the occurrence of larger skin lesions at the site of the primary horse serum injections, the earlier development of more distinct secondary reactions in a higher percentage of animals, and by the more rapid appearance of skin sensitivity to the small test doses which may be first evidenced by delayed reactions at these injection sites. Accompanying these evidences of increased reactivity, there is an early appearance of blood serum precipitins in high titer.

4. There was no evidence of residual inflammation in any of the animals at the time reactivity to horse serum was tested. No attempt was made to determine the duration of this altered reactive capacity. It has been encountered in tests begun from 8 to 14 days after the last preliminary inoculation.

5. It is suggested that the increased reaction described is brought about by a persisting alteration in the functional activity of the reticulo-endothelial system.
THE INFLUENCE OF SEXUAL MATURITY UPON THE REACTIVITY OF RABBITS TO HORSE SERUM
Authors: Schultz Mark P.
Published: June 2004

1. Normal rabbits in the course of their development, after infancy, vary in their responses to minute doses of horse serum given intracutaneously.

2. There is increased reactivity in males as they mature, beginning, in the stock employed in these experiments, at about the age of 13 weeks when a weight of 1,700 gm. has been attained.

3. The reactivity of normal females remains at a constant level and the increase demonstrated in males does not take place.

4. The divergence in degree of reactivity between males and females, beginning with the establishment of estrus, indicates that factors associated with sexual maturity in females are responsible for their low reactivity.

5. The suppression of estrus by operative removal of the ovaries results in an increase of reactivity which, however, in the experiments reported here is probably not great enough to account entirely for the difference in reactivity between mature males and females.
BACTERIOLOGICAL STUDIES ON AN EPIZOOTIC OF INTESTINAL DISEASE IN SUCKLING AND NEWLY WEANED MICE
Authors: Syverton Jerome T. , Olitsky Peter K.
Published: June 2004

It is now quite generally conceded that the presence in animals of bacteria of Salmonella type is indicative of an active, or potentially active, pathogenic agent (26). In the present instance bacteriological studies of the organs of acutely ill infant mice revealed the presence of one of the Salmonella group. It showed itself to be such by an absence of fermentation of lactose and saccharose, by other cultural reactions, and by cross-agglutination with certain members of the Salmonella group in very low dilutions of their antisera.6 However, the bacterium cannot be included in any of the known species of the group because of its indol-forming properties, differences in carbohydrate reactions, and specific serological reactions. Its presence in affected mice, growth on artificial media, ability to cause the disease following enteral and parenteral inoculations, and the fact that it can be recovered from artificially infected mice fulfill the postulates of Koch. Furthermore, agglutinins are present in the blood of recovered mice and not in that of normal animals, and recovery of mice from natural infection evokes an apparent resistance against the special recovered Salmonella bacterium. The organism would appear to fall in the Asiaticusdivision of the genus, as designated by Castellani and Chalmers (27).
THE METABOLISM OF COPPER AND IRON IN SPLENECTOMIZED RATS FREE FROM BARTONELLA MURIS INFECTION
Authors: Sandberg Marta , Perla David
Published: June 2004

Removal of the spleen in albino rats free from Bartonella muris infection is followed by an increased elimination of copper in the feces, which commences 2 weeks after splenectomy. This is associated with a persistent negative copper balance.

An increased retention of iron occurs during a period of 4 to 6 weeks after splenectomy with a return of the iron metabolism to normal after this period.

No disturbance in creatine or creatinine metabolism occurs. The uric acid amount is unchanged. There is an increase in the retention of nitrogen, which is first noted 3 weeks after splenectomy.

The spleen is essential for the utilization of copper in the body.
RABBIT POX
Authors: Greene Harry S. N.
Published: June 2004

The lesions found in animals with epidemic rabbit pox have been described in this paper. The most distinctive gross lesion in all organs and tissues was the small nodule or papule which was found to consist of mononuclear infiltration and necrosis. Diffuse lesions were also found in which the infiltration was widespread and accompanied by edema, hemorrhage and extensive necrosis of affected tissues and organs. The possibility of the diffuse lesions being due to the action of secondary invaders was considered, but available evidence indicated that the different types, including pneumonia, represented reactions to a single causative agent. Moreover, an intimate relationship was observed to exist between lesions and small blood vessels in which primary endothelial damage was usually apparent. The degree of vascular damage generally corresponded to the extent of the lesion and it is probable that this in turn corresponded to the dose of the causative agent.

The close analogy between the clinical manifestations and pathological processes of this disease in the rabbit and small pox in man led to the conclusion that the disease in the rabbit is essentially the same as small pox, and that it is probably produced by a virus closely related to the virus of small pox. Available evidence indicated that the infection originated in the Institute and that it spread in atypical form or masked by some other disease until it reached the breeding colony as a clearly defined epidemic infection.
BIOLOGICAL STUDIES OF THE TUBERCLE BACILLUS
Authors: Steenken W. , Oatway W. H. , Petroff S. A.
Published: June 2004

1. The H37 strain of human tubercle bacillus has been dissociated into two variants,—the R, or avirulent, and the S, or virulent, variants.

2. When their dissociation is complete, colony morphology for each is distinctive and typical.

3. The morphology of the individual bacilli of the two variants is different and characteristic.

4. The R variant develops best in an acid medium; the S develops best in an alkaline medium.

5. A method of assortment to facilitate the procedure of forced dissociation has been described.

6. The difference in virulence has been proven by observations on the pathogenesis of the variants.
HEMORRHAGES IN SKIN LESIONS OF GUINEA PIGS FOLLOWING INTRAVASCULAR INJECTION OF TOXINS (SHWARTZMAN PHENOMENON)
Authors: Freund Jules
Published: June 2004

1. Filtrates from B. coli, B. typhosus, or meningococci injected into the skin of guinea pigs do not produce visible inflammation. When these injections are followed by intravascular injections of the same material, hemorrhages do not occur in the skin.

2. Guinea pigs sensitized to horse serum react with redness and edema to 0.1 or 0.01 cc. of horse serum injected into the skin, and subsequent intravascular injection of typhoid filtrate does not produce hemorrhage at the site of the reaction to horse serum.

3. When guinea pigs are injected into the skin with diphtheria toxin and these injections are followed by intravascular injection of filtrates from B. typhosus, hemorrhage occurs in the skin at the site of the reaction to diphtheria toxin.

4. When silver nitrate is injected into the skin of guinea pigs, redness, edema, and necrosis follow, and in a few guinea pigs small areas of hemorrhage can also be noticed. About half of the guinea pigs that have received an intravascular injection of typhoid filtrate react with hemorrhage at the site of the injection of silver nitrate.
A VIRUS-INDUCED MAMMALIAN GROWTH WITH THE CHARACTERS OF A TUMOR (THE SHOPE RABBIT PAPILLOMA)
Authors: Rous Peyton , Beard J. W.
Published: June 2004

Rabbit papillomas developing on the skin as the result of virus inoculation can be readily transferred to the inner organs of favorable hosts by implanting bits of the living tissue. The growths thus produced proliferate actively as a rule and frequently cause death. Often they are markedly invasive and destructive; and they tend to recur after excision. Bacterial infection may greatly enhance their malignancy. Accidental dissemination may occur during operation, and distribution to the peritoneal surface has been repeatedly noted. There may be no cellular reaction whatever about the invading epithelium of interior growths, but usually some new formation of connective tissue takes place, its amount varying inversely with the rate of epithelial proliferation. An immediate reason exists for the inflammatory changes and scarring found beneath long-established skin papillomas, in the trauma and secondary infection to which the projecting, necrotizing masses have been subjected. In animals dying of progressively enlarging interior growths the skin papilloma may long have been stationary in size.

The growths appearing after the transfer of papillomatous tissue to the inner organs are due to the survival and multiplication of transplanted cells. However, the virus can be readily recovered from them, in the case of wild rabbits. No distinctive changes in the blood of the host have been found. The virus itself is highly specific for the epithelium of the skin, failing to act not only upon that of the other organs thus far tested but even upon embryonic skin.

The papilloma frequently penetrates into the blood and lymph vessels, especially at the edge of implantation growths. The intravascular injection of fragments of it sometimes results in pulmonary nodules of characteristic morphology. These are due to survival and proliferation of the injected cells. Secondary nodules have been encountered at autopsy in a lymph gland and in the lungs, but under conditions more suggestive of operative dissemination of the growth than of true metastasis.

Implantation growths of the papilloma in favorable hosts have the morphology of epidermoid tumors of greater or less malignancy. They behave as these do and elicit similar changes in the surrounding tissue.

The attributes and potentialities of the papilloma will be further considered in Papers II and III.
A VIRUS-INDUCED MAMMALIAN GROWTH WITH THE CHARACTERS OF A TUMOR (THE SHOPE RABBIT PAPILLOMA)
Authors: Rous Peyton , Beard J. W.
Published: June 2004

Experimental study of the rabbit papilloma of Shope, a growth caused by a virus, has shown that it possesses the immediate characters whereby tumors are recognized. Often it looks and acts like a malignant neoplasm. It differs from the tumors as a group, however, in its incidence which is that of an infectious process, and from other mammalian tumors in that its cause has been demonstrated. The possible bearing of the findings upon the problem of tumor causation is discussed. The morphology and behavior of the generality of tumors can no longer be taken to exclude the possibility that these are produced by extraneous, living entities. The incidence of some of the tumors at least, and the failure to demonstrate their cause can both be explained on the assumption that they are due to such entities, widely distributed in or upon the animal population but effective only under special circumstances. Present knowledge makes this assumption reasonable as a basis for further work.
II. HEMOGLOBIN AND BILE PIGMENT OVERPRODUCTION IN THE SPLENECTOMIZED BILE FISTULA DOG
Authors: Knutti R. E. , Hawkins W. B. , Whipple G. H.
Published: June 2004

Blood destruction associated with Bartonella or with a drug (hydrazine) in bile fistula dogs yields a large pigment excess. These dogs form large amounts of new hemoglobin and bile pigment on a diet which permits of but little new hemoglobin production in standard anemic dogs.

When hemoglobin formation and hemoglobin destruction are occurring rapidly and simultaneously, estimations of the percentage of circulating hemoglobin alone, though showing the eventual total increase or decrease of this substance, do not permit one to determine the actual amounts formed or destroyed.

It is suggested that the body can produce readily a large amount of the pyrrol aggregate (four pyrrol rings) which may go to form new hemoglobin. At the same time the globin is probably saved from destroyed red cells and turned over into new hemoglobin for new red cells.

It is certain that globin may be a determining factor under certain circumstances in the construction of new hemoglobin for new red cells. Our knowledge about the construction and internal metabolism of globin is extraordinarily limited.
THE DEMONSTRATION OF A TUMOR GROWTH-INHIBITING FACTOR FROM NORMAL HUMAN CONNECTIVE TISSUE
Authors: Morton John J. , Beers Daniel N.
Published: June 2004

Extracts from fresh normal human connective tissue (rectus sheath) exhibited a decided inhibiting action on grafts of Rat Tumor 256 transplanted into test animals. There was complete inhibition of tumor growth in 66 per cent of the animals; there was a marked retardation in the rate of growth in another 15 per cent, the tumors in these instances being much smaller than the controls transplanted at the same time. In only one experiment was there failure to obtain a lasting growth-inhibitory effect. The tumors in these animals (19 per cent) although showing an initial retardation in growth, apparently overcame the restraint and at the end of 5 weeks were larger than the control series. Extracts from fresh normal human muscle tissue, on the other hand, showed no such inhibiting action on grafts of Rat Tumor 256.
STUDIES ON ANAPHYLAXIS WITH POLLEN
Authors: Bernstein Clarence
Published: June 2004

1. Guinea pigs injected intracutaneously and subcutaneously with extract of the pollen of burweed marsh-elder in relatively small amounts did not show anaphylactic response to intravenous shock doses of this material 3 weeks later.

2. If, however, the animals were sensitized with horse serum either before, or along with the same pollen injections, they could then be shocked after an interval of 3 weeks with pollen extract alone.

3. The possible rôle of this underlying sensitivity is discussed.
THE EXPERIMENTAL PRODUCTION IN DOGS OF ACUTE STOMATITIS, ASSOCIATED WITH LEUCOPENIA AND A MATURATION DEFECT OF THE MYELOID ELEMENTS OF THE BONE MARROW
Authors: Miller D. K. , Rhoads C. P.
Published: June 2004

An ulcerative stomatitis associated with leucopenia and granulopenia can be induced in dogs by means of a diet causing black tongue. The decrease of circulating leucocytes is due to a suppression of maturation of the erythropoietic elements of the bone marrow. The changes as a whole have a resemblance to those occurring in human beings with acute agranulocytosis.
THE SEROLOGICAL DIFFERENTIATION OF PATHOGENIC AND NON-PATHOGENIC STRAINS OF HEMOLYTIC STREPTOCOCCI FROM PARTURIENT WOMEN
Authors: Lancefield Rebecca C. , Hare Ronald
Published: June 2004

1. The majority of strains of hemolytic streptococci from puerperal infections of the uterus were identified serologically as members of the Group A described by Lancefield.

2. The majority of strains isolated from the birth canal of women whose puerperium was afebrile were not members of Group A.

3. The existence of two new serological groups of hemolytic streptococci, Groups F and G, is described.
GRADING OF LOCAL SKIN REACTIVITY TO BACTERIAL FILTRATES
Authors: Shwartzman Gregory
Published: June 2004

In this paper there are described methods for grading the local skin reactivity induced by bacterial filtrates. The grading is accomplished by titration of the skin-preparatory factors; and by studies on the duration of ensuing reactivity.

It was found that the duration of reactivity depends upon the mode of preparation of filtrates and the microorganisms employed. Thus, it lasts for 96 hours with meningococcus "agar washings" filtrates; for 72 hours with B. typhosus "agar washings" filtrates; it disappears within 48 hours with B. typhosus tryptic digest broth culture filtrate and B. typhosus "agar washings" filtrates previously heated in the Arnold sterilizer for 20 minutes.

Comparative titrations of the preparations employed demonstrate that the duration of reactivity is in direct relationship to the reacting potency.

It is also shown that the skin-preparatory potency of the filtrates and the duration of the ensuing local reactivity are not modified by cellular anaphylactic sensitization (Arthus phenomenon) to animal proteins.

The exposure of tissues to the effect of certain soluble bacterial factors induces a high susceptibility to humoral toxic principles resulting from intravascular antigen-antibody interaction.
FURTHER STUDIES WITH TOXIC SERUM EXTRACTS OF HEMOLYTIC STREPTOCOCCI
Authors: Weld Julia T.
Published: June 2004

1. The same Streptococcus hemolyticus organisms may be subjected to extraction six times in 2 days with untreated inactivated serum with no loss in potency of the later extracts when the organisms are kept frozen solid during the night between the extractions.

2. The serum extract toxins of hemolytic streptococci can be preserved without deterioration for at least 6 months if kept frozen solid.

3. No toxins stronger than those containing 10 units per cc. for mice have been prepared. Reasons for thinking that this is due to the saturation of the serum with the toxin at this point are given.

4. Half saturation with (NH4)2SO4 precipitates out practically all of the hemotoxin in a preparation.

5. Serum extracts were made from strains of hemolytic streptococci other than the Gay strain and attempts were made to correlate the virulence and toxin production from each strain. No such correlation could be established.

6. The principal pathologic finding in mice inoculated with the streptococcus serum extract toxin is a marked degeneration of the tubular epithelium of the kidney.