bluuebunny/crossref_metadata_2025 huggingface dataset:
IMMUNITY STUDIES OF ROCKY MOUNTAIN SPOTTED FEVER
Authors: Noguchi Hideyo
Published: June 2004

Freshly prepared mixtures of spotted fever virus and immune rabbit serum in neutral or superneutral proportions confer complete immunity on guinea pigs.

The mixtures undergo a considerable loss in immunizing power when heated to 60°C. for 20 minutes, but are still capable, if used in sufficient quantity, of conferring a degree of immunity on the vaccinated animal such that a subsequent experimental infection is rendered less severe and non-fatal.

Unheated mixtures which had been preserved in the refrigerator at 4°C. for a period of 32 days still retained a certain degree of immunizing property.

The virus alone, or mixed with normal rabbit serum, when allowed to die out by prolonged preservation at refrigerator temperature, or when killed either by heating at 60°C. for 20 minutes or by chemicals (chloroform, ether, xylene) does not induce immunity in guinea pigs.
ROENTGEN RAY INTOXICATION
Authors: Warren S. L. , Whipple G. H.
Published: June 2004

These experiments show that the common laboratory animals are about equally sensitive to the x-ray given over the abdomen. The clinical reaction following a M.L.D. is very similar and the intestinal pathology almost identical. The rat and guinea pig are slightly more sensitive to the x-ray than are the dog, cat, and rabbit.

By contrast birds, frogs, and reptiles are very resistant to the x-ray and may tolerate two or three doses of radiation lethal for dogs. We can offer no convincing explanation for this fact which is discussed above.

These data strengthen our belief in the scattered and incomplete observations on human cases which indicate that the human intestinal tract is likewise sensitive to radiation. This fact must be given careful consideration in conditions where abdominal or pelvic radiation is being used because such injury done to intestinal epithelium is always serious and in some cases irreparable.
OBSERVATIONS ON SOME CAUSES OF GALL STONE FORMATION
Authors: Rous Peyton , McMaster Philip D. , Drury Douglas R.
Published: June 2004

Gall stones frequently form in dogs intubated for the collection of bile under sterile conditions, in the absence of stasis and of gall bladder influence. The stones consist almost entirely of two substances—calcium carbonate and calcium bilirubinate—and they are remarkably uniform in character, as would follow from the limiting conditions of their development. They are not the result of bile loss, for similar ones may be recovered from the wall of glass tubes interpolated in ducts with intestinal connection undisturbed. The study of them has brought out evidence on the general problem of cholelithiasis. Some factors in their causation and that of gall stones as a class will be considered in succeeding papers.
OBSERVATIONS ON SOME CAUSES OF GALL STONE FORMATION
Authors: Rous Peyton , Drury Douglas R. , McMaster Philip D.
Published: June 2004

A day-to-day study has been made of the sediment in the sterile liver bile of intubated dogs. There exists a marked tendency for calcium carbonate to be deposited therefrom. After hepatic or duct injury a great deal of organic débris of various sorts may be present in the bile, but it never causes deposition out of the fluid save when it accumulates in quantity on the tube wall. Particles of the material of which "bile thrombi" are composed may be found in the bile when the liver has been appropriately damaged, but these fail to act as centers of stone formation. On the other hand, there are to be found in the secretion after many sorts of hepatic injury little nuclei which undoubtedly serve in this way. These nuclei consist of a mixture of calcium bilirubinate and carbonate with an organic shadow or scaffolding. They do not occur in normal bile, but, coming down on special occasions, prove favorable to deposition out of the secretion elaborated at later periods. We have found nuclei strikingly similar in their relationship to stone formation, but consisting almost wholly of carbonate, in the sterile bile from human gall bladders which contained large calculi. Many of them were encountered in a free state, and others with layers of cholesterol and organic matter upon their surface, while others yet were recognizable deep within matured stones.

The factors concerned in the genesis of gall stones consisting of calcium carbonate have been reviewed at some length in this paper and the preceding one. The evidence we have collected supports the view that the development of carbonate stones in human beings as well as in the dog may be a consequence, not of changes in the bile brought about by microorganisms, nor of the elaboration of an inflammatory exduate rich in calcium salts, but merely of inflammation such as leads to lessened motility of the duct system with the accumulation of organic débris. The fact that infection is almost the sole agent whereby such inflammation is set up and maintained in clinical instances had led too often to the conclusion that it serves as the essential agent in the process of calcification.

The present findings taken with those described in a preceding paper suffice for an understanding of the immediate history of the gall stones which develop in intubated dogs. But the factor of individual differences, as yet undefined in nature, bulks large in the problem of the lithiasis, as does that of the local physiological safeguards against it.
STUDIES ON PNEUMOCOCCUS GROWTH INHIBITION
Authors: Robertson Oswald H. , Sia Richard H. P.
Published: June 2004

Somewhat discordant results which have been reported by others who have investigated the property of the whole blood of resistant animals to cause inhibition of growth or death of pneumococci have led us to investigate this matter and to develop a new technique in which the conditions as they are present in the animal body are more nearly imitated. The observations already made have rendered it probable that phagocytosis plays some rôle in any destructive power for pneumococcus which whole blood possesses. We have, therefore, employed mixtures of serum and leucocytes in our tests, since when blood is coagulated the conditions become highly artificial. Furthermore, in order to imitate more nearly the conditions in the circulating blood the mixtures have been constantly, though gently, agitated. For this purpose a specially devised apparatus has been employed. The mixtures of serum and leucocytes have been inoculated with varying numbers of pneumococci in the active growth phase and after varying intervals of time the tubes containing the mixtures of serum, leucocytes, and bacteria have been opened, examined microscopically, and cultures made.

Employing this technique it has been found that the growth of pneumococci having low virulence for cats is markedly inhibited in mixtures of cat serum and cat leucocytes. It was impossible to recover pneumococci from the tubes showing no apparent growth, either when the contents were transplanted into various kinds of culture media, or when the contents were injected into mice of a variety highly susceptible to pneumococcus infection. 10,000 times the number of pneumococci sufficient ordinarily to kill a mouse failed to do so after a 24 hour sojourn in the cat serum-leucocyte mixture. Mixtures of dog serum and leucocytes exert a similar action. The serum and leucocytes of animals susceptible to pneumococcus infection (rabbits and guinea pigs,) on the other hand, failed to injure pneumococci even in extremely small quantities.

These results indicate that the blood of resistant animals, at least of the dog and cat, possesses destructive properties for pneumococci, and that this destructive power is not possessed by the blood of certain susceptible animals. The experiments suggest that natural immunity depends chiefly, if not entirely, upon this property. The leucocytes play an active part in this process, but whether the destruction of the pneumococci occurs entirely within the leucocytes or not is not determined. That the serum also plays a part is shown by the fact that when the serum of resistant animals was inactivated before being used in the serum-leucocyte mixture, the growth of even very small numbers of pneumococci was not prevented.

Further experiments with cat serum and leucocytes were carried out to determine the optimum rate and time of agitation, the amount of serum and leucocytes required, and also the period of incubation necessary for the inhibition of growth and death of the pneumococci to occur.
THE RELATION BETWEEN THE INGESTION OF COLOSTRUM OR BLOOD SERUM AND THE APPEARANCE OF GLOBULIN AND ALBUMIN IN THE BLOOD AND URINE OF THE NEW-BORN CALF
Authors: Howe Paul E.
Published: June 2004

The coincidence of the appearance of euglobulin and pseudo-globulin I in the blood and urine of the new-born calf following the ingestion of colostrum and the absence of these proteins when milk is fed support the inference that the proteinuria of the new-born calf is due to the ingestion of colostrum. In this passage the proteins are in part unaltered.

The absorption and excretion of the proteins of blood serum have been observed.

The high protein content of the feces of young calves—during the first few days—is to be ascribed, in part at least, to ingested colostrum.
THE INFLUENCE OF THE ADRENAL GLANDS ON RESISTANCE
Authors: Scott W. J. M.
Published: June 2004

1. The resistance of rats to bacterial intoxication is greatly decreased after double adrenalectomy.

2. This decreased resistance is dependent upon a functional insufficiency of the adrenal cortex.

3. A dose of killed streptococci or staphylococci can be obtained that is invariably fatal to adrenalectomized rats, before hypertrophy of cortical accessories, but never kills control rats.
THE EFFECT OF PILOCARPINE ON THE NUMBER OF SMALL LYMPHOCYTES IN THE CIRCULATING BLOOD FOLLOWING LIGATION OF THE THORACIC DUCT
Authors: Lee Ferdinand C.
Published: June 2004

In a series of animals in which the thoracic duct had been tied it was found that the relative increase in the number of small lymphocytes in the circulating blood following the intraperitoneal administration of pilocarpine nitrate was the same as for the control animals. While support is brought for Harvey's view that pilocarpine causes a lymphocytosis through the contraction of plain muscle, on the other hand evidence is presented which indicates that the spleen is no more specialized in the production of small lymphocytes than any other portion of the lymphopoietic system.
STUDIES ON THE RELATION BETWEEN TUMOR SUSCEPTIBILITY AND HEREDITY. I
Authors: Lynch Clara J.
Published: June 2004

In this preliminary report there are presented some of the results obtained from crossing mice from tumor strains with males from other sources. The comparison of the tumor incidence in the inbred and backcross daughters, though the numbers given are small, supports the theory that the tendency to develop neoplasms is hereditary and the frequency with which tumors appear in the first filial generation of such crosses, indicates that the character is dominant.

Additional experiments involving larger numbers are in progress.
THE PATHOGENESIS OF RHEUMATIC FEVER
Authors: Swift Homer F.
Published: June 2004

It is evident that there are two distinct types of response on the part of the body to the infectious agent of rheumatic fever; viz., proliferative and exudative. The perivascular proliferative type of lesion, resembling an infectious granuloma, explains the subacute and chronic character of the clinical symptoms in many patients with this disease. Marked exudation of serum into the periarticular tissues and of serum and cells into the joint cavities are concomitants of the acute arthritis occurring with high fever and general intoxication; these acute exudations disappear following the administration of certain drugs. But their disappearance does not mean necessarily that all lesions of the proliferative type have resolved. In fact, we know that these last mentioned lesions, when present in the subcutaneous tissues, often continue for months; and from analogy we may conclude that they have a similar persistent character in other tissues of the body invaded by the causative agent of rheumatic fever.
THE EFFECT OF DIGESTIVE JUICES ON THE POTENCY OF BOTULINUS TOXIN
Authors: Bronfenbrenner Jacques J. , Schlesinger Monroe J.
Published: June 2004

Botulinus toxin resists a degree of acidity equivalent to that of the stomach even when exposed thereto for 24 hours at 37°C. It is less resistant to alkali, however, as shown by the fact that in a medium of weakly alkaline reaction its potency is reduced to less than one-tenth in 24 hours. It is unaffected by peptic and tryptic digestion. Because of its instability in mildly alkaline solutions and resistance to acid, there is reason to believe that the toxin is in the main absorbed from the upper portion of the digestive tract; that is to say, from the stomach and upper duodenum.
EXPERIMENTS ON THE SURVIVAL OF THE FEBRILE HERPETIC AND ALLIED VIRUSES IN VITRO
Authors: McCartney James E.
Published: June 2004

These studies fail to confirm the statements previously made that microorganisms of the class of the globoid bodies of poliomyelitis may be cultivated in the Smith-Noguchi medium from the so called virus of encephalitis lethargica. They show equally that the herpes virus does not multiply in this medium. The experiments indicate, moreover, that the medium is unfavorable to the survival of the virus, while ordinary broth under aerobic conditions is more favorable for maintaining the activity of both the encephalitic and the herpes viruses. Probably no multiplication of either takes place in the latter medium but merely a survival, and for a maximum period of 6 days in the broth itself, and 12 days in the fragment of brain tissue immersed in the broth. Finally, it has been shown that with a suitable technique the viruses can be passed from the brain of one rabbit to that of another through a long series without contamination with cocci or other common bacterial forms. Hence we regard all reports of the finding of ordinary bacteria in the brain of cases of epidemic or lethargic encephalitis as instances of mixed or secondary infection arising during life, or examples of postmortem invasion of the body, or of faulty technique at the autopsy.
STUDIES ON OXIDATION AND REDUCTION BY PNEUMOCOCCUS
Authors: Avery Oswald T. , Neill James M.
Published: June 2004

1. Sterile broth extracts of unwashed pneumococci, entirely free from living or intact cells, actively reduce methylene blue.

2. Sterile extracts prepared by extracting washed pneumococci in phosphate solution are unable by themselves to reduce methylene blue. Upon the addition of meat infusion or yeast extract, these washed cell extracts actively reduce methylene blue.

3. The system or systems in pneumococcus extracts responsible for methylene blue reduction are destroyed by exposure to temperatures practically identical with those which have been previously found to destroy the peroxide-forming activity of the same extracts.

4. It is suggested that peroxide formation and methylene blue reduction by pneumococcus extracts are functions of the same or closely related systems, the particular reaction induced depending upon whether molecular oxygen or methylene blue serves as hydrogen acceptor or oxygen donator.
EXPERIMENTAL OBSERVATIONS ON THE "CURE" OF SYPHILIS IN THE RABBIT WITH ARSPHENAMINE
Authors: Chesney Alan M. , Kemp Jarold E.
Published: June 2004

1. The intravenous administration of six doses of arsphenamine to syphilitic rabbits in amounts of 10 mg. per kilo, 127 days after inoculation is sufficient to render the popliteal nodes of such animals incapable of transmitting the infection to normal animals.

2. Syphilitic rabbits that have been treated in this manner and whose popliteal nodes 32 to 38 days after treatment have been shown to be incapable of transmitting the infection to normal animals are, as far as can be judged by the absence of a local lesion, refractory to a second inoculation of active virus of the same strain, if the inoculation be made intradermally at the base of the ear and carried out 209 days after the first inoculation.

3. Untreated syphilitic rabbits are also refractory toward a second inoculation made in a similar manner and at a similar interval following the first inoculation.

4. Evidence is offered in favor of the view that the most satisfactory method of evaluation of antisyphilitic agents in experimental syphilis of the rabbit is that of lymph node transfer.

5. Evidence is offered in support of the view that the state of refractoriness toward a second inoculation exhibited by syphilitic rabbits may be explainable upon the basis of either an acquired immunity or persistence of a focus of living treponemata in the body.
THE CORRELATION OF CERTAIN PHENOMENA OCCURRING DURING THE GROWTH OF PNEUMOCOCCUS
Authors: Morgan Hugh J.
Published: June 2004

The growth of a culture of pneumococcus was followed together with the time relations of some of the phenomena incident thereto. There were, roughly speaking, three periods of growth: first, the period of maximum rate, or logarithmic period; second, a brief stationary period; and third, the period of decline, during which actual death of individual organisms in the culture occurred. It has been pointed out that the usual preliminary latent period was avoided by the use of relatively large inoculum, obtained from a culture which was itself in the logarithmic period of growth.

During the height of growth activity of the culture certain changes in the substrate became demonstrable. Between the 7th and 10th hours the reaction of the medium was changed by the production of acid and the soluble specific substance was detected. At a somewhat later time in the logarithmic period of the culture peroxide was demonstrable and, simultaneously with the appearance of this substance, the substrate acquired the ability to change catalase-free crystalline hemoglobin to methemoglobin. Moreover, changes then occurred in the cultural fluid, such that, after the removal of the parent organisms by filtration, it no longer supported growth when seeded with either the pneumococcus or staphylococcus. These changes occurred early in the logarithmic period of growth of the culture.
THE INTERACTION OF TWO FRAGMENTS OF PULSATING HEART TISSUE
Authors: Fischer Albert
Published: June 2004

Fragments of heart from the same species, when cultivated in vitro, are capable of uniting and pulsating synchronously. This happens not only in fragments derived from the same heart but with those from different individuals of the same species. It was not possible, on the other hand, to obtain, under the conditions of experiment, any physiological union of a heart fragment from a duck embryo with one from a chicken embryo, though both pulsated in the same medium and though the tissue cells of the duck were capable of growth and multiplication.

From the experiments it is evident that cell contact is essential for the development of physiological identity as just described. Since such a physiological identity cannot be obtained through the union of a fragment of a duck heart and a fragment of a chicken heart, one may suppose that anastomosis between the cells must play a very significant rôle in it.
THE DIFFERENTIATION AND KERATINIZATION OF EPITHELIUM IN VITRO
Authors: Fischer Albert
Published: June 2004

The organization, or, according to Drew, differentiation, of epithelial cells grown in vitro is not due to a specific influence of the associated connective tissue. It occurs in all old pure cultures of epithelium, when the tissue fragment becomes thick and suffers from lack of oxygen and nourishment. Under the same circumstances, keratinization occurs in cultures of epithelium.
EXPERIMENTAL STUDIES WITH A SPIRAL ORGANISM FOUND IN A WILD RAT
Authors: Mooser H.
Published: June 2004

1. Two cases of rat-bite fever with a typical fever course and a maculopapular exanthem came under my observation in Mexico.

2. A spiral organism morphologically identical with one known in Japan as the causative agent of Sodoku was found in a Mus decumanus caught in Mexico City.

3. The organism was found to be pathogenic for white rats and guinea pigs, the infection being fatal for guinea pigs.

4. The bite of an infected guinea pig led in one of two instances to infection and death of the animal bitten.

5. The microscopical findings in the guinea pigs infected with this microorganism closely resemble in many respects the findings in Blake's case and in Kaneko and Okuda's first case, the only ones of human rat-bite fever which have been closely studied at post mortem.

6. Eye lesions were found in all the infected guinea pigs and the spiral organisms were demonstrated in the discharge from the eyes and also within the cornea.

7. Similar eye lesions were found in most of the infected rats and the secretion from the eyes of one of them was demonstrated to be infectious for guinea pigs.

8. The eye lesions constitute an evident source for the spiral organisms transmitted by biting, and not improbably the only one.

My experiments may give an explanation for the transmission of some other spirochetal diseases besides rat-bite fever. Cases of Weil's diseases are reported to be caused by the bite of a rat and it is noteworthy that eye lesions occur in spirochætosis icterohæmorrhagica (Manson).
THE REVERSE SELECTIVE BACTERIOSTATIC ACTION OF ACID FUCHSIN
Authors: Burke Victor , Skinner Charles E.
Published: June 2004

1. The reverse selective action attributed to acid fuchsin can be explained on the basis of spore resistance. This action does not apply to the vegetative cells of Gram-positive spore bearers. It cannot be extended to include the Gram-negative spore bearers.

2. The selective action of acid fuchsin is that of an ordinary weak disinfectant and is not comparable to the selective action of the triphenylmethane dyes.

3. A lack of parallelism between the bactericidal and bacteriostatic action of acid fuchsin can be explained on the basis of spore resistance and it does not exist when spores are excluded.

4. Acid fuchsin is a weaker disinfectant than basic fuchsin for both Gram-negative and Gram-positive bacteria. The process of sulfonation by which acid fuchsin is made from basic fuchsin results in a reduction in the bactericidal action of the dye for Gram-negative and Gram-positive bacteria.

5. The most significant fact in the action of the dyes on bacteria is the toxic effect of the triphenylmethane dyes on Gram-positive spore-bearing organisms.
AN IMMUNIZING STRAIN OF THE VIRUS OF POLIOMYELITIS
Authors: Flexner Simon , Amoss Harold L.
Published: June 2004

In this communication we have described a strain of the virus of poliomyelitis derived from a rapidly fatal human case, which exhibits mild degrees of infective power and marked degrees of protective effect for the monkey. While Macacus rhesus displays perceptible differences in suceptibility to the attenuated virus, nearly all individuals respond to the inoculation and none succumbs to the infection induced. As compared with previously described examples of experimental poliomyelitis, the modified disease described in this paper is distinguished by its relatively benign nature and its tendency to end in recovery rather than, as with the earlier observed instances, in death.
EXPERIMENTS ON ANAPHYLAXIS TO AZOPROTEINS
Authors: Landsteiner K.
Published: June 2004

From the experiments which have been reported, it follows that animals sensitized with one azoprotein react not only to the antigen used for the sensitization, but also to other azoproteins made up from the same simple azo-compounds and another protein. Although the specificity of the reaction has not yet been tested with various azo-components, its actual existence can reasonably be assumed on the basis of the phenomena observed in precipitation reactions. The sensitization is brought about with less facility than sensitization against the usual antigens and the effects are not uniform. Still, after sufficient treatment, 40 per cent of the animals succumbed with typical anaphylactic symptoms, mostly within a short time while 16 per cent showed severe symptoms.

The experiments show that it is possible to make animals hypersensitive against a simple chemical group like para-arsanilic acid, and from this point of view connection would seem to be established with the phenomena of drug allergy in human beings.

There is an essential difference, however, in that the sensitized animals did not react on injections of simple compounds such as para-amino-phenyl-arsanilic acid and phenyl-4-arsonic-acid-azo-tyrosine uncombined with protein. It remains to be determined whether under changed conditions positive results in this direction can be obtained. For this purpose it seems advisable to make experiments with isolated organs, according to the method of Schultz and Dale. While the simple substances failed to elicit direct reactions, they protected (as was foreseen by Doerr) against a subsequent injection of the active antigen. Similar compounds not containing the arsanilic acid group were considerably less active. The phenomenon is comparable to the inhibition of precipitin reactions already described. Considering the protection as a condition of antianaphylaxis, one would suppose that the simple substances mentioned are fixed by the cells in which the anaphylactic reaction takes place.

It may be concluded that:

1. Animals can be sensitized through injections of one azoprotein—protein combined with diazotized para-arsanilic acid—against another compound containing the same azo-component but a different protein.

2. Injections of related simple compounds, as for instance para-arsanilic acid and phenyl-4-arsonic-acid-azo-tyrosine did not cause shock in the sensitized animals under the conditions of the present experiments.

3. The simple compounds mentioned and other related substances as well protect against the anaphylactic action of azoprotein, by inducing a state of antianaphylaxis.
STUDIES ON THE RESPIRATORY MECHANISM IN LOBAR PNEUMONIA
Authors: Binger Carl A. L. , Brow George R.
Published: June 2004

1. The functional residual air (defined as the lung volume at the end of normal expiration) has been determined in a series of normal individuals and in ten patients with lobar pneumonia at different stages of the disease.

2. The rate, depth, and minute volume of respirations were measured in the same individuals by a graphic method.

3. When appreciable cyanosis was present the oxygen content and capacity of the arterial blood were determined.

4. A constant relationship has been found to exist between the persistence and disappearance of symptoms (fever, accelerated heart rate, rapid and shallow breathing, cyanosis) and fluctuations of the functional residual air. When these symptoms persisted the functional residual air decreased; during their disappearance the volume of the functional residual air rose towards normal. The rise was detected soon after the crisis.

5. A close parallelism has been observed also between alterations in radiographic shadow, physical signs, and the volume of the functional residual air. The lung volume, measured at normal expiration, is diminished during the persistence of pathological signs in the lungs, and returns to normal as the pathological signs disappear. The average time required, in cases which recovered, for the functional residual air to become constant was 11 to 12 days, counting from the onset of the disease.
THE RELATION OF BLOOD PRESSURE TO THE AMOUNT OF RENAL TISSUE
Authors: Anderson Hilding C.
Published: June 2004

The removal or destruction of about 70 per cent of the kidney tissue in rabbits does not produce hypertension even when prolonged renal insufficiency results.
THE INFLUENCE OF RESISTANCE ON THE CHARACTER OF DISEASE IN EXPERIMENTAL RESPIRATORY INFECTION
Authors: Jones F. S.
Published: June 2004

An organism of the Pasteurella group (Pasteurella avicida) has been shown to possess considerable pathogenicity for rabbits when injected into the trachea. 1 cc. of bouillon containing 1/100 cc. of a 24 hour bouillon culture introduced by means of a curved metal tube passed through the larynx gives rise to a rapidly fatal septicemia in which the lungs are not particularly involved. Rabbits may be made completely resistant to this intratracheal infection by means of intratracheal, intraperitoneal, or subcutaneous injections of killed cultures. Vaccination and subsequent injection of living culture beneath the skin resulted in extensive abscess formation about the site of inoculation. Vaccines sprayed on the mucous membranes of the nose and throat failed to raise appreciably the resistance against subsequent intratracheal injection.

Rabbits whose resistance has been stimulated within narrow limits by a small dose of vaccine beneath the skin become more resistant to the experimental respiratory infection. The character of the disease is changed from a rapidly fatal septicemia without lung involvement to a more prolonged pneumonia. The blood remains sterile for varying periods. Consolidations of the more dependent lobes occur with considerable regularity. In two instances a characteristic empyema developed in the course of the experiments.
STUDIES ON OXIDATION AND REDUCTION BY PNEUMOCOCCUS
Authors: Avery Oswald T. , Neill James M.
Published: June 2004

In the present work on oxidation and reduction by sterile extracts of pneumococcus, the preparations employed contain among other constituents, a hemolytic substance the properties of which have been described by Cole (1, 2) in his studies on pneumococcus hemotoxin. Pneumococcus extracts prepared by the methods described are actively hemolytic, 0.005 cc. of extract causing complete lysis of 2.5 cc. of a 1 per cent suspension of red cells from rabbit blood. This hemolytic property of pneumococcus extracts is destroyed by 10 minutes exposure to 55°C. When pneumotoxin-containing extracts are protected from the action of molecular oxygen, their hemolytic activity remains unimpaired for considerable periods of time. In the presence of air, on the other hand, the stability of the hemolytic substance depends upon whether the particular type of extract contains a "complete" or "incomplete" oxidation-reduction system. Sterile broth extracts of unwashed pneumococci are reactive with molecular oxygen, and as a result of this union peroxide is formed whenever these extracts are exposed to air. The hemolytic activity of "complete" extracts of this type is rapidly decreased and finally destroyed in the presence of molecular oxygen. On the other hand, the "incomplete" type of extract prepared by saline extraction of washed pneumococci may be exposed to air with little or no loss of hemolytic power. This "incomplete" washed cell extract, unless reactivated, does not undergo autoxidation in the presence of air; under these circumstances peroxide is not formed and the hemolytic activity of this type of extract is not impaired by exposure to air. The stability of the hemolytic agent in the "incomplete" type of extract is evidence that this substance is itself not reactive with or affected by molecular oxygen, even in the presence of the cell enzymes. The destruction of the same hemolytic substance in extracts capable of undergoing autoxidation may be ascribed to the action of some peroxide formed by the union of molecular oxygen with easily oxidized or autoxidizable substances of the extract. It is now known that a peroxide, having the reactions of hydrogen peroxide, accumulates in sterile pneumococcus extracts during oxidation. It has been shown in the present study that the addition of preformed hydrogen peroxide destroys the hemolytic activity of pneumococcus extracts, although higher concentrations were required than were detected in oxidized extracts themselves. These facts and the known action of superoxides in analogous types of reaction make it seem not unlikely that the active agent in the destruction of pneumotoxin in oxidized cell extracts may be a peroxide; either hydrogen peroxide or some higher organic peroxide formed during autoxidation of the extract.
THE EPIDEMIOLOGY OF A RABBIT RESPIRATORY INFECTION
Authors: Webster Leslie T.
Published: June 2004

The bacteria constituting the nasal flora of rabbits at The Rockefeller Institute may be enumerated as follows in the order of their frequency: (1) Micrococcus catarrhalis group, 80 per cent; (2) Bacterium lepisepticum, 70 per cent; (3) Gram-negative cocci which ferment dextrose, lactose, saccharose, maltose, and mannite, but not salicin and Bacillus bronchisepticus, 40 per cent; (4) Staphylococci, streptococci, and various intestinal bacilli which probably are localized at the external nares, 10 per cent.

Bacterium lepisepticum is the predominating organism in the nasal passages of the rabbits affected with snuffles.
THE CONCENTRATION OF THE PLASMA PROTEINS IN NEPHRITIS
Authors: Linder G. C. , Lundsgaard C. , Van Slyke D. D.
Published: June 2004

In nephrosclerosis (Volhard and Fahr classification of nephritis) there was no decrease in the plasma proteins. With heart failure the ratio of albumin to globulin fell from the normal 1.7 ± 0.3 to about 1.

There is a sharp difference between the two types of glomerulonephritis in the effect on plasma proteins. In the vascular-interstitial type the effect was the same as in nephrosclerosis. There was no decrease in the plasma proteins until shortly before death.

In the glomerulotubular or nephrotic type, active or recently active, the total plasma proteins were less than 5 gm. per 100 cc. This decrease from the normal 5.5 to 7.5 occurred whether edema was present or absent. The decrease affected chiefly the albumin, the globulin being usually diminished but little, and sometimes slightly increased. Consequently the ratio of albumin to globulin was reduced to less than 1, and occasionally to 0.6.

In nephrosis similar changes were found in the total protein concentration but in severe cases the decrease in albumin was greater than in nephrotic glomerulonephritis while the globulin was either very slightly reduced or was increased. The albumin : globulin ratio was therefore lower than in nephrotic glomerulonephritis, ranging down to 0.26.

With the disappearance of edema there was usually an increase in the plasma protein concentration, but this was not invariable, and concentrations of 4.5 per cent or less were compatible with the persistent absence of edema. The ratio of albumin to globulin showed an irregular tendency to rise. Whenever the total concentration was less than 4 per cent there was some edema present, but it was sometimes slight in amount.

With recovery in acute cases, and remission with decrease of proteinuria in chronic cases, normal concentrations were regained. The albumin : globulin ratio remained low in some instances for a longer period on account of an absolute increase in globulin concentration.

In "functional proteinuria" no change in plasma proteins was found.

Low plasma protein concentrations were always associated with considerable losses of protein in the urine, but these losses did not provide an explanation for all our observations. A disturbance in the production of the plasma proteins appears probable.
FAT METABOLISM IN NEPHRITIS
Authors: Hiller A. , Linder G. C. , Lundsgaard C. , Van Slyke D. D.
Published: June 2004

Determinations of the plasma lipoids and of the respiratory quotient and total metabolism (Tissot method) have been performed with nephritics and normal subjects before and after they ingested fat in the proportion of 1 gm. per kilo body weight.

After fat ingestion a greater increase of fatty acids and lecithin was noted in the plasma of nephritics with initially high blood lipoids than in the plasma of normal subjects or of nephritics without constant lipemia. In cholesterol no differences were found.

The nephritic patients with constant lipemia were able to burn fat as efficiently as normal individuals.

The accumulation of fat in their blood may be due to a disturbance in the mechanism for transferring lipoids from the blood to the tissue depots.
ACTION OF FORMALDEHYDE ON ENZYMES AND ON CERTAIN PBOTEIDS
Authors: Bliss C. L. , Novy F. G.
Published: June 2004

The following general conclusions may be drawn from the preceding work:

Fibrin is altered by formaldehyde and is then less easily digested by pepsin and by trypsin. Papaïn is apparently unable to digest fibrin even when this is exposed to very weak formaldehyde (1:1000) for a very short time.

The casein of milk, on contact with formaldehyde, undergoes rapid alteration and is as a result not coagulated by rennet, or but very slowly. Such altered casein, like similar fibrin, is not readily digested by the proteolytic ferments. The longer the formaldehyde acts on casein and on fibrin the more marked is the result.

Pepsin is not affected by a one per cent solution of formaldehyde, even when the mixture has stood for four weeks. Even a five per cent solution of formaldehyde acting for three weeks has no effect on pepsin. Contrary results obtained by others are due to an alteration of the fibrin by the formaldehyde. A putrid solution of pepsin in distilled water one month old digests fibrin as readily as a fresh solution.

Rennet is not affected even by a four per cent solution of formaldehyde acting for several weeks. The absence of coagulation at times is due to the action of formaldehyde on the casein of the milk and not on the rennet ferment.

Papaïn is very quickly altered by formaldehyde, even in very dilute solution. Moreover, it is unable to digest fibrin that has been exposed to the action of a very dilute solution of formaldehyde for a short time.

Trypsin is altered by formaldehyde to such an extent that digestion of fibrin will not take place, or but very slowly. The extent to which trypsin is affected by formaldehyde depends largely upon the amount of organic matter present, as well as on the amount of ferment in the solution.

Amylopsin is not destroyed by very dilute solutions of formaldehyde, but stronger solutions decrease the activity of the ferment, and if used in sufficient concentration will destroy it completely.

Ptyalin, like the diastatic ferment of the pancreas, is not destroyed by dilute solutions of formaldehyde. If the latter is used in rather strong concentration and allowed to act for some time it will destroy the ferment. The action of formaldehyde is more rapid and more marked at a slightly elevated temperature than at ordinary room temperature.

Malt diastase, unlike the diastatic ferments of the saliva and pancreatic solution, is not destroyed by formaldehyde when this is used in moderate amount and at ordinary temperature. Unlike pepsin, a solution of malt diastase readily undergoes decomposition on standing even for one or more days. This destruction is undoubtedly due to bacteria since it does not take place when formaldehyde is present. Consequently the favoring action which formaldehyde apparently exerts on diastase really consists in the inhibition of the growth of micro-organisms, and hence the diastase is protected against decomposition.
STUDIES ON THE TOTAL BILE
Authors: McMaster Philip D.
Published: June 2004

The development of a method for the collection of total bile from dogs in a sterile state and uninfluenced by the gall bladder, day after day for weeks, has rendered possible an accurate study of the influence of diet upon the cholesterol output of the secretion.

When a diet rich in cholesterol is given the amount of the substance in the bile greatly increases. Not only this but the concentration per cc. is, in almost every instance, greater. An increase in the total food intake, by the addition to the ordinary ration of a bone mash diet containing only a slight additional amount of cholesterol (200 mg.) produces a similar, though lesser, increase. In the fasting dog, the cholesterol yield is greatly cut down.

The increase in the cholesterol after food rich in the substance does not depend on the cholagogue action of this latter, though it is true that the concentration of cholesterol in the bile usually increases with the bile volume.

Though fasting cuts down the cholesterol of bile, the concentration of the substance per cc. is greatly increased. On an ordinary diet the yield of it fluctuates abruptly and considerably from day to day. In general the rule holds that an animal eating largely puts out not only much more bile but much more cholesterol. The relation between bile quantity and cholesterol yield is anything but a fixed one, however.

The cholesterol yield of the bile does not parallel that of bilirubin. The pigment output from day to day remains relatively constant as compared with that of cholesterol.
THE PERMEABILITY OF THE LINING OF THE LOWER RESPIRATORY TRACT FOR ANTIBODIES
Authors: Jones F. S.
Published: June 2004

The experimental results indicate that the walls of the lower respiratory tract are relatively as impermeable for antibodies as they are for serum proteins. The kind of serum employed does not influence this fact. Antibodies contained in homologous (rabbit) serum failed to enter the blood stream when injected into the trachea in greater concentration than those contained in heterologous (guinea pig and cow) sera.

That a little serum and its contained substances are absorbed after intratracheal injection has been shown both by the experiments dealing with sensitization and anaphylaxis previously reported and by the experiments recorded in this paper.

Besredka's assertion that the laryngotracheal method is an efficient one for the administration of serum in the treatment of disease has not been borne out by the experimental evidence here presented. From the results one would conclude that it is one of the least efficient routes for administration.

In contrast to the relative impermeability for proteins of the mucous membranes of the lower respiratory tract is the relative permeability of the endothelium of the peritoneal cavity. Antibody is there absorbed readily, whether it be in heterologous or in homologous serum. The indications are that a considerable portion of the antibody injected into the peritoneal cavity reaches the blood stream in 2 or 3 hours.
CAUSE OF IMMEDIATE DEATH BY LARGE DOSES OF BOTULINUS TOXIN
Authors: Bronfenbrenner Jacques J. , Schlesinger Monroe J. , Orr Paul F.
Published: June 2004

Parenteral introduction of amounts of the culture filtrate of Bacillus botulinus greatly in excess of the minimum lethal dose has been observed to cause the practically immediate death of mice. This result is due to the presence in the filtrates of a chemical poison possessing properties distinct from those of the contained botulinus toxin which itself acts only after a well defined period of incubation. This chemical poison is not neutralized by botulinus antitoxin; it is effective only when large amounts of the culture filtrate are given; it is thermostable, not being destroyed when heated in the autoclave in a sealed tube, though when it is heated in an open container its toxicity diminishes with a coincidental volatilization of basic material. The volatile substance can be identified as ammonia.

Death resulting from the injection of comparatively large amounts of ammonium salts (0.1 gm.) is easily distinguished from that due to botulism, both through the character of the symptoms and the absence of an incubation period. However, when the amount of toxic salts injected is smaller (0.01 gm.), the symptoms of poisoning are not so characteristic and death may be delayed long enough to suggest a period of incubation similar to that observed in botulism (Table IV). This circumstance is of importance in connection with the examination of partly decomposed food products in which the presence of botulinus toxin is suspected. As a rule such suspected material is injected in massive doses (0.5 to 1 cc.) in mice. It is conceivable that such spoiled foods may be contaminated with common putrefactive bacteria yielding ammonia during their growth and thus may cause death of the test animals. If in such tests mice passively protected by the preliminary injection of an excess of antitoxin be used in addition to normal animals, the chances of an error in the interpretation of the results will be materially reduced, though not ruled out. Unfortunately for such a procedure, botulinus antitoxin is not readily available, while furthermore, recent findings indicate that it may not always be effective owing to the existence of a group of toxin-producing bacteria very similar to Bacillus botulinus, but not homologous immunologically with either of the known types of the latter.

The test of thermostability of the toxic constituents of suspected food may conceivably help to determine the true nature of the poison.
ON THE SPECIFICITY OF AGGLUTININS AND PRECIPITINS
Authors: Landsteiner K. , van der Scheer James
Published: June 2004

The results of the partial saturation of precipitins with antigens related in derivation to the homologous one give no conclusive evidence of the regular existence in a single immune serum of multiple antibodies which act specifically on various chemical groups of the antigenic proteins. It seems possible to explain at least a part of the facts by the assumption that a single antibody will react to different degrees with several similar substances.

By the partial absorption of hemagglutinins with heterologous blood, specific fractions were obtained. By such means one may readily differentiate the blood of related species, even when precipitins show but little difference.

The peculiarities in specificity manifested by precipitinogens and agglutinogens suggest an essential difference in the chemical structures which determine the specificity of the two kinds of antigens.