bluuebunny/crossref_metadata_2025 huggingface dataset:
THE ASSOCIATION OF PNEUMOCOCCI, HEMOPHILUS INFLUENZAE, AND STREPTOCOCCUS HEMOLYTICUS WITH CORYZA, PHARYNGITIS, AND SINUSITIS IN MAN
Authors: Webster L. T. , Clow A. D.
Published: June 2004

Pneumococci, H. influenzae, and S. hemolyticus are known to be frequent inhabitants of the upper respiratory tract, but most workers have not recognized any definite relationships between their presence and coryza, sore throat, influenzal, and sinusitis attacks (2–5). Dochez, Shibley, and Mills, however, in their experimental studies of common cold, state that in both the spontaneous and experimentally induced "colds" in anthropoid apes, the "most significant change observed has been the increase of activity on the part of the potential pathogens habitually present in the throat flora. Coincident with the appearance of symptoms, pneumococci, S. hemolyticus, and B. pfeifferi have developed in greatly increased numbers and have spread over a wide area of the nasopharyngeal mucous membranes. These organisms became at this time conspicuous even in the nose, where they are seldom or never present under normal conditions. The same phenomena have not been observed in human beings" (6, 7).

The essential facts of the present observations are that persons free of pneumococci, H. influenzae, and S. hemolyticus are in general free of coryza, sore throat, influenzal and sinus attacks; that persons who are occasional or periodic carriers of these organisms may be negative on tests over long healthy periods, but generally become positive during or following attacks and subsequently become negative again; finally, that persons who are chronic carriers show during these illnesses increasing numbers of organisms in the throat and extension of the organisms to the nose.

That these organisms may be the actual incitants has been claimed by Park (8); that they are secondary invaders is the view of Shibley, Mills, and Dochez who state as a result of their experimental work on this subject that "the most important significance of viruses of this type [common cold] seems to lie in their capacity to incite activity on the part of the more dangerous pathogenic organisms that infect the upper respiratory tract" (7). The present observations bring out the intimate relationship between these pathogens and upper respiratory tract symptoms, but do not disclose the nature of this relationship.

Finally, an addition has been made to the knowledge of the mode of spread of these organisms. A focus of growth and dissemination has been determined in the nasal passages and throat of individuals with chronic upper respiratory tract disease and increases in numbers of the organisms at the focus and their spread to contacts have been related to the winter season and to the occurrence of symptoms in the carrier. The observations suggest that the dosage of these organisms in a community is controlled by the resistance of the carrier and of the contacts. This view is in agreement with the facts derived from studies of native animal infections (9).
THE EFFECT OF TESTICLE EXTRACT ON THE GROWTH OF TRANSPLANTABLE MOUSE TUMORS
Authors: Tanzer Radford C.
Published: June 2004

Grafts of a transplantable mouse sarcoma designated as No. 180, and those of an attenuated strain of a more malignant Sarcoma S/37, treated with testicle extract, either fail to grow on inoculation or result in tumors of a lower growth rate than the controls. Autografts of spontaneous mouse tumors so treated show little if any effect, while the Bashford adenocarcinoma and the unattenuated S/37 are unaffected. The factor in testicle extract responsible for the retarding activity passes readily through a Berkefeld filter and is thermostable.
STUDIES ON THE NATURE OF THE AGENT TRANSMITTING LEUCOSIS OF FOWLS
Authors: Furth J. ,   With the Assistance of Charles Breedis and Ruth Klingelhofer
Published: June 2004

The concentration of the transmitting agent of leucosis in fowls, as determined by titration, is approximately the same in the suspensions of blood cells and in cell-free plasma; the smallest amount of plasma producing leucosis was 0.000001 cc. and of cell suspension 0.00001 cc. This observation excludes the possibility that transmission of leucosis by plasma is due to the presence of a small number of leucemic cells in the plasma.

The success of inoculations with plasma (20 to 28 per cent of fowls) is, within wide limits, independent of the amount injected (10–1 to 10–6 cc.). The percentage of successful inoculations with varying quantities of plasma is lower than with corresponding amounts of suspensions of cells (33 to 71 per cent).

When plasma containing the transmitting agent is injected in decreasing amounts the incubation period of the leucosis is conspicuously lengthened. With decreasing amounts of a suspension of leucemic cells the incubation period is not so frequently nor so greatly prolonged.
STUDIES ON THE NATURE OF THE AGENT TRANSMITTING LEUCOSIS OF FOWLS
Authors: Furth J. ,   With the Assistance of Clara B. Taylor and Charles Breedis
Published: June 2004

The filterable agent transmitting leucosis resists drying, retaining its activity for at least 54 days. The conditions of successful desiccation have not been precisely ascertained. By the addition of glycerin the agent can be preserved for at least 104 days. It is not inactivated by freezing in liquid air. At 37.5°C. it loses its activity within 14 days, but retains some of its activity for at least 14 days when kept at 4°C.
INFLUENCE OF LIGATION OF PANCREATIC DUCTS OF DOGS UPON SERUM AMYLASE CONCENTRATION
Authors: Johnson Carl E. , Wies Carl H.
Published: June 2004

A sharp contrast has been demonstrated in regard to the post-operative amylase concentration of the sera of dogs, depending upon whether ligation of the pancreatic ducts was or was not a part of an otherwise prescribed operation. The characteristic feature is a marked rise of several hundred per cent in serum amylase concentration, sustained for several days, which is observed when the pancreatic ducts have been ligated.
AN EXAMINATION OF THE MECHANISM OF PNEUMOCOCCUS IMMUNITY BY MEANS OF BACTERICIDAL MEASUREMENTS
Authors: Ward Hugh K.
Published: June 2004

1. Type III antipneumococcus serum, after absorption with the specific carbohydrate, no longer forms a precipitate with the carbohydrate, but still has a definite, though diminished bactericidal action on virulent pneumococci in a bactericidal test.

2. Such an absorbed antiserum still retains some of its power to neutralize the antibactericidal effect of the specific carbohydrate in a bactericidal test, showing that absorption with the carbohydrate does not remove all the anticarbohydrate antibody from an antiserum.

3. This carbohydrate neutralization test is a very much more delicate method for detecting the anticarbohydrate antibody (precipitin) than the precipitin test.

4. There is therefore no necessity to predicate another antibody to explain the bactericidal action of a carbohydrate-absorbed antiserum, or a similar result in a mouse protection test.

5. The specific carbohydrate has a definite antibactericidal action, but it is demonstrated that, were it present in this form in the body during pneumonia, it could not conceivably be produced in sufficient quantity to influence the disease.
AN EXAMINATION OF THE MECHANISM OF PNEUMOCOCCUS IMMUNITY BY MEANS OF BACTERICIDAL MEASUREMENTS
Authors: Ward Hugh K.
Published: June 2004

1. There is in the filtrate of a 5 day broth culture of Type III pneumococcus a type-specific substance which has a very powerful antibactericidal action. If the precipitinogen content of the broth filtrate and the specific carbohydrate is taken as the basis of comparison, it requires approximately one thousand times as much antiserum to neutralize the broth filtrate as is necessary to neutralize the specific carbohydrate. The active substance in the broth filtrate appears to be related to the specific carbohydrate. Its possible nature is discussed.

2. A similar substance, but in stronger concentration, was found in the filtrate of a lung from a Type III pneumonia autopsy. The influence of this substance on the disease is discussed.

3. One specimen of Type III convalescent blood, though comparatively weak in anticarbohydrate antibody (precipitin) was better able to neutralize the broth filtrate and the lung filtrate than a corresponding mixture of normal blood and antiserum. Two other specimens of Type II convalescent blood neutralized the Type III broth filtrate efficiently.
THE FURTHER SEPARATION OF TYPES AMONG THE PNEUMOCOCCI HITHERTO INCLUDED IN GROUP IV AND THE DEVELOPMENT OF THERAPEUTIC ANTISERA FOR THESE TYPES
Authors: Cooper Georgia , Rosenstein Carolyn , Walter Annabel , Peizer Lenore
Published: June 2004

The unclassified strains known as Group IV have been separated into twenty-nine types which are designated by the Roman numerals IV and XXXII. Only a small percentage of the pneumococcus strains isolated in New York City for this study were left unclassified.

The majority of the types gave very slight cross-reactions, the exceptions being Types II and V, III and VIII, VII and XVIII and XV and XXX.

In the series of cases studied, Types IV, V, VII and VIII were found more prevalent in the lobar pneumonia of adults and Types V, VI a and XIV in children.

The majority of the types were also found in normal individuals and in persons having respiratory infections other than pneumonia. Types VI a and XIX were most prevalent in the limited number of strains studied by us.

Fourteen of the types were found in pneumococcus meningitis; Type XVIII was found most often.

Antisera suitable for clinical trial have been prepared for fourteen types. From the majority of the horses inoculated for more than a year, antisera having 500 to 1000 units per cc. were obtained. Antisera of lower potency were concentrated and preparations obtained equal to or stronger than high grade unconcentrated serum.

Potent bivalent antisera have been prepared for types which were found to give marked cross-agglutination reactions.

The results with each type as to prevalence, severity of cases, presence in normal individuals, and in spinal meningitis, potency of antisera produced for therapeutic trial and virulence of strains for mice have been considered under the different type headings.
QUANTITATIVE STUDIES ON THE PRECIPITIN REACTION
Authors: Heidelberger Michael , Kendall Forrest E.
Published: June 2004

A method, based on the precipitin reaction, is given for the micro determination of the specific polysaccharide of Type III pneumococcus. As little as 0.01 mg. of S III can be determined. The method should be applicable to any specific polysaccharide upon standardization of an homologous antibody solution or antiserum in the region of excess antibody.
STUDIES ON THE CULTIVATION OF THE TYPHUS FEVER RICKETTSIA IN THE PRESENCE OF LIVE TISSUE
Authors: Nigg Clara , Landsteiner K.
Published: June 2004

1. Rickettsia prowazeki can be cultivated for many generations in vitro, without diminution in numbers or virulence, in media similar to those described by Maitland, Rivers, and others for the cultivation of certain viruses. In all probability, such cultures can be maintained indefinitely.

2. It has been impossible, thus far, to cultivate the typhus rickettsia without employing living tissue.
THE MAINTENANCE OF A NORMAL PLASMA PROTEIN CONCENTRATION IN SPITE OF REPEATED PROTEIN LOSS BY BLEEDING
Authors: Barnett C. W. , Jones R. B. , Cohn R. B.
Published: June 2004

1. Experiments on five dogs are described consisting in the daily removal of blood plasma in amount from 25 to 100 cc. the red cells being returned to the circulation in Locke's solution. In no case was there a significant drop in plasma protein concentration.

2. A gravimetric method for the determination of total plasma protein is described.

3. A case is reported of cirrhosis of the liver in which over 10 gm. of protein daily was lost in the ascitic fluid during a period of 7 months without any lowering of plasma protein concentration.

4. The constancy of the plasma protein level and the adequacy of the mechanism of regeneration is pointed out.
THE EFFECTS OF PARATHORMONE AND AMMONIUM CHLORIDE ON THE BONES OF RABBITS
Authors: Jaffe Henry L. , Bodansky Aaron , Blair John E.
Published: June 2004

1. A very large single dose of parathormone produced rapid and extensive decalcification of the bones of a young rabbit.

2. Gradually increased doses of parathormone failed to produce significant changes in the bones of young and fully grown adult rabbits.

3. Ammonium chloride, administered by stomach tube was without effect on the bones, when given to rabbits treated with parathormone or to otherwise untreated rabbits.

4. Calcium lactate did not promote the appearance of signs of parathormone overdosage in rabbits during treatment, nor were metastatic calcifications observed in the soft tissues after termination of the experiment.

5. The rabbit is relatively very resistant to the decalcifying effects of gradually increased repeated doses of parathormone, and therefore is not satisfactory material for experimental studies of bone changes of chronic hyperparathyroidism.

6. The appearance of actively transforming bones of a young growing rabbit, particularly at the sites of rapid growth, is not to be confused with the more severe fibrous processes produced by parathormone in guinea pigs, dogs and rats.
THE RACES THAT CONSTITUTE THE GROUP OF COMMON FIBROBLASTS
Authors: Parker Raymond C.
Published: June 2004

1. The ability of fibroblasts to mature and to manifest their various potencies in any particular medium is inversely proportional to the growth energy which they exhibit in that medium. Fibroblasts having access to high concentrations of food substances in their environment do not mature, regardless of their origin or the age of the animal from which they were derived. They behave as embryonic cells.

2. Fibroblasts cultivated in vitro are potentially able to produce cells with the structural and functional properties commonly attributed to macrophages. This is true regardless of their origin or the length of time which has elapsed since their isolation from the origin.

3. The fibroblast and the macrophage are considered to represent extreme functional and structural variations of the same cell type.

4. The structural and functional characteristics displayed by fibroblasts in vitro vary according to their origin and to the changes which take place in the composition of the medium in function of time.
ON THE SEROLOGICAL SPECIFICITY OF PEPTIDES
Authors: Landsteiner K. , van der Scheer J.
Published: June 2004

With the idea that studies on the serological properties of peptides may ultimately aid in the understanding of the precipitin reactions of proteins, antigens have been prepared containing aminobenzoylated dipeptides, namely glycyl-glycine, glycyl-d, l-leucine, d, l-leucyl-glycine and d, l-leucyl-d, l-leucine. These four antigens were found to be different serologically, their specificity depending on the structure of the terminal amino acid carrying the free carboxyl group, and to a less degree also on the second amino acid. The results were obtained by means of precipitin and inhibition tests. Analogies to observations on enzyme specificity are discussed.
CORNEAL REACTIONS TO BACTERIUM GRANULOSIS AND OTHER MICROORGANISMS
Authors: Olitsky Peter K. , Knutti Ralph E. , Tyler Joseph R.
Published: June 2004

The conclusions which may be drawn from the results of the experiments here presented are:

1. The cornea of the rabbit is highly sensitive to the action of various injected bacteria. The lesions vary from insignificant, transient changes to severe, destructive panophthalmitis, with fine gradations from the mildest to the violent form of inflammation. Moreover, animals that receive the same organisms show like changes.

2. The varying degree of inflammatory reaction is related to the pathogenicity of the special culture employed; as, for example, is shown by the reactions to Type I pneumococci and to Bacterium granulosis. It is evident that when a microorganism having a certain degree of virulence is used, a lesion of localized vasculonebulous keratitis resembling pannus tenuis or vasculosus of human trachoma can be induced. Thus Bacterium granulosis, Bacillus xerosis, Hemophilus influenzae, Pneumococcus Type II, Streptococcus viridans, and gonococcus can cause the pannus-like corneal changes in the rabbit. Of these organisms, however, only Bacterium granulosis induces early, uncomplicated and enduring keratitic lesions; the others cause first, diffuse keratitis with suppurative lesions; then, as a residual effect, transient, localized, vasculonebulous changes in the cornea. These changes, in contradistinction to the granulosis lesions, are, therefore delayed, complicated, and transient. When, on the other hand, the invasiveness and infecting power of the organisms are low, as is the case with the filtrable, Gram-negative bacillus and the small, Gram-negative bacilli ultimately derived from cases of folliculosis, no marked effect is produced by their intracorneal inoculation. If the pathogenicity of bacteria is high (as shown by Pneumococcus Type I, hemolytic streptococcus, and the remaining bacteria), intracorneal inoculation of the microorganisms leads to serious suppurative or destructive changes.

3. The results of experiments with monkeys indicate that while pannus is not a sequel of experimental trachomatous conjunctivitis, a lesion resembling it follows intracorneal inoculation of Bacterium granulosis.

4. One can infer from these results, therefore, that the stimulus necessary to produce corneal changes in animals, similar to those of trachomatous pannus, is an agent having a definite but extremely low power of invasiveness and infectivity.
THE PURIFICATION AND CONCENTRATION OF DIPHTHERIA TOXOID
Authors: Wadsworth Augustus , Quigley James J. , Sickles Gretchen R.
Published: June 2004

By precipitation with acetone at 4°C. a refined diphtheria toxoid was obtained as a dry powder, readily soluble in aqueous solutions. The powder itself appears to be stable. When dissolved in half the original volume of physiological salt solution, the toxoid remained stable, in the cold room, for a period of 7 months. Only toxoids should be used which have been completely detoxified by the treatment with formalin. The formalin is immediately and completely removed by precipitation with acetone.

Filtration through a Mandler filter or the addition of a preservative did not appear to have any deleterious effect.

Incubating at 39°C. and freezing for 20 hours did not impair its activities.

The flocculating value of the purified toxoid containing phenol was almost completely destroyed by freezing, while when merthiolate was the preservative, it was unchanged.

Approximately 62 per cent of the nitrogen was eliminated in the process with approximately 15 per cent loss in flocculating value.

The flocculating values were nearly double those of the original material and thus corresponded with the concentration, which was onehalf the volume. By this method, the antigenic activity of a toxoid below standard may be increased to a satisfactory standard. The antigenic activity of the refined product in the immunization of guinea pigs may in general parallel its flocculating values but the relation between the results of these tests may not be proportional nor constant. As an immunizing agent in the guinea pig, the refined toxoid possesses an antigenic activity that is equal to, or greater than, that of the unconcentrated toxoid.
COMPARISON OF THE REDUCING POWER OF SOME TYPICAL TRANSPLANTABLE TUMORS AND OF TUMORS PRODUCED BY FILTERABLE VIRUSES
Authors: Barron E. S. Guzman
Published: June 2004

1. The tissues of Rous chicken sarcoma and of the infectious myxoma of the rabbit do not possess the oxidation-reduction enzyme succinodehydrogenase, which is present in normal tissues and in transplantable tumors.

2. Filterable virus diseases (rabbit Virus III, rabbit neurovaccine, rabbit herpes, fowl-pox) produce in the tissues affected by them a partial inhibition of succinodehydrogenase.
SPONTANEOUS AND ACQUIRED ACTIVE IMMUNITY TO THE PHENOMENON OF LOCAL SKIN REACTIVITY TO BACTERIAL FILTRATES
Authors: Shwartzman Gregory
Published: June 2004

Spontaneous active immunity to the phenomenon of local skin reactivity to bacterial filtrates has been demonstrated. In one experiment, the immunity was non-specific, while in others it appeared limited to one or two bacterial species.

Intradermal vaccination of rabbits with bacterial filtrates induced active immunity to the phenomenon. The specificity of this immunity was tested with graded amounts of toxic factors. The combined intradermal and intravenous immunization in these experiments elicited two types of response:—

1. Specific immunity, which was obtained in rabbits highly susceptible to the phenomenon (i.e., showing reactions with 1 reacting unit).

2. Non-specific immunity which was elicited in rabbits with partial spontaneous immunity (i.e. showing no reactions with 1 reacting unit, but susceptible to 15 units 1 week later). Comparative studies on the reacting potency of "agar washings" and disintegrates (Besredka's method, freezing and thawing method) showed that the first washings of bacterial cells are considerably stronger than subsequent washings and disintegrates. These facts demonstrate once again the extracellular nature of the material necessary for the phenomenon.

Tentative explanations of the mechanisms involved in the specific and non-specific immunity to the phenomenon are discussed.
A VIRUS DISEASE OF PARROTS AND PARRAKEETS DIFFERING FROM PSITTACOSIS
Authors: Rivers Thomas M. , Schwentker Francis F.
Published: June 2004

The virus of parrots and parrakeets discovered by Pacheco, Bier, and Meyer is unrelated to the agent causing psittacosis either in birds or in man. The virus is fairly species-specific and manifests itself chiefly by the production of areas of focal necrosis in the liver and acidophilic intranuclear inclusions in affected cells.
THE THERAPEUTIC VALUE OF INTRAMUSCULAR DOSAGE OF TYPE I PNEUMOCOCCUS ANTISERA
Authors: Curphey Theodore J. , Baruch Herman B.
Published: June 2004

1. Intramuscular dosage of antipneumococcus sera in a standard dermal pneumococcic infection in rabbits is as effective as intravenous dosage provided the degree of blood stream invasion be not unusually high.

2. The immediate bactericidal effect of doses of serum given intramuscularly is equal to that of the same doses given intravenously in the cases of mild and moderately severe bacteremias.

3. The intramuscular method of serum administration in human beings with lobar pneumonia deserves a carefully controlled clinical trial.
VIBRIOS FROM THE INTESTINAL TRACT OF THE GRAY RAT
Authors: Jones F. S. , Little Ralph B. , Orcutt Marion
Published: June 2004

Vibrios obtained from the intestinal tracts of wild rats are described. The organism is a normal inhabitant of the lower ileum and cecum of the rat and may be cultivated from these regions. While these rat organisms are in their growth characters and morphology like those found in an intestinal disease of cattle they differ serologically from the cow organisms.
THE ANEMIA OF SCURVY
Authors: Mettier Stacy R. , Chew William B.
Published: June 2004

1. Weight loss, progressive anemia, and a moderate increase in reticulated red blood cells occurred in seventeen guinea pigs on a diet deficient in vitamin C.

2. The histological changes of the bone marrow removed from guinea pigs with scurvy showed large numbers of erythrogenic cells, but scant evidence of active maturation to the adult erythrocyte.

3. A reticulocyte response was induced in guinea pigs with scurvy when fed orange juice daily.

4. The histological changes of the bone marrow removed from guinea pigs during the reticulocyte response showed large numbers of mitotic figures and relatively more adult red blood cells than in the bone marrow from guinea pigs with scurvy that had not been treated with orange juice.

5. It is concluded from this study that the anemia of experimentally induced scurvy in the guinea pig is largely dependent upon vitamin C deficiency resulting in retarded maturation of the red blood cell.
STUDIES ON GALL BLADDER FUNCTION
Authors: Riegel Cecilia , Johnston C. G. , Ravdin I. S.
Published: June 2004

The data obtained from the experiments on dogs reported in this paper lead us to conclude that bile pigment is not absorbed from the gall bladder bile. The mean loss of pigment is so small when compared with the amount of water lost that it is negligible.

Our cholesterol data do not support the concept that this substance is secreted into the gall bladder bile of the dog under normal conditions. In the majority of experiments there was a loss of cholesterol. Indeed we have failed to find any evidence of definite secretion or absorption save in the case of the infected gall bladder. We are led to conclude, as did Rous and McMaster (15) with regard to bile pigment, that normally there is no absorption of cholesterol.
PROPERTIES OF THE CAUSATIVE AGENT OF A CHICKEN TUMOR
Authors: Murphy James B. , Sturm Ernest
Published: June 2004

The presence of an inhibiting substance in the chicken tumor is shown by the fact that a desiccate of the tumor is more active after it has been washed two or three times with water, and that an extract of the tumor is more potent after some factor is removed by adsorption on aluminum hydroxide.

When the tumor-producing factor in an extract of a slow-growing tumor has been destroyed by heating at 55°C. it is found to have the property of neutralizing a highly active tumor extract. This inhibiting property is destroyed by heating over 65°C.
PROPERTIES OF THE CAUSATIVE AGENT OF A CHICKEN TUMOR
Authors: Murphy James B. , Sturm Ernest , Favilli Giovanni , Hoffman Donald C. , Claude Albert
Published: June 2004

The injection of tumor extracts and their active protein fractions into rabbits induced the formation of precipitins and neutralizing antibodies. When the major portion of proteins in the tumor extract had been eliminated it induced the formation of neutralizing antibodies, but not of precipitins. The tumor agent, more highly purified by removal of the viscous fraction, did not induce precipitins, and only 2 out of the 15 sera gave any evidence of neutralizing bodies. After the removal of the major portion of protein, the extracts showed insufficient interaction with the sera to fix complement.
STUDIES ON VIRULENCE
Authors: Felton Lloyd D.
Published: June 2004

From the study of different tissue extracts as media for the growth of pneumococci used in an automatic transfer device, certain inferences are warranted:

1. Media made from calf lung or heart, or from horse skeletal muscle maintain virulence over a long period of time. Conversely, media made from calf spleen lead to a decrease in virulence.

2. Lung medium causes an increase in virulence of seven strains of pneumococci.

3. Virulence is maintained in normal horse serum; but, it rapidly decreases in immune serum, or in pneumococcus antibody solution, a finding which confirms the work of Stryker. Immune serum freed from protective antibody gives results similar to normal serum.

4. Rabbit medium made from the entire animal apparently is less suitable for the maintenance of virulence of pneumococci than medium made in the same way from guinea pig.
TYPHUS FEVER
Authors: Pinkerton Henry , Hass G. M.
Published: June 2004

In tissue cultures grown at 32°C., typhus Rickettsiae increase rapidly within the cytoplasm of infected cells up to about the 14th day. At this time practically every cell is infected and the majority of cells are distended with organisms.

This condition remains constant as long as successful cultures of the cells can be maintained (up to 52 days).

Loss in virulence does not take place during this period in vitro.

The number of Rickettsia-filled cells found in sections and the incubation period of the infection resulting from inoculation of cultures from each age group are definitely correlated.

The behavior of typhus Rickettsiae in dividing cells is described and methods of spread of the infection other than by mitosis of cells are discussed.

Normal tissues do not become infected in vitroto any considerable extent in spite of prolonged proximity to heavily infected cultures of scrotal sac exudate.

Complete anaerobiosis and alterations in pH do not alter the intracellular location of the organism in tissue cultures.

The organisms are not seen within nuclei of infected cells. They remain intact and infective for several weeks in cells which are kept alive but not multiplying. They disappear in less than 1 week, however, when the cells undergo degeneration.
SPOTTED FEVER
Authors: Pinkerton Henry , Hass G. M.
Published: June 2004

Spotted fever infection has been studied in tissue cultures grown at 32°C. The behavior of spotted fever Rickettsiaeis compared and contrasted with that of typhus Rickettsiae under similar conditions. The spotted fever organisms multiply extensively in the nuclei of cells where they form spherical clusters of various sizes. These structures are compared and contrasted with intranuclear inclusion bodies.
STUDIES ON VIRULENCE
Authors: Felton Lloyd D.
Published: June 2004

The growth of a virulent Type I pneumococcus in an automatic transfer device on a medium which aerobically maintains virulence results in a decrease in the presence of pure oxygen or pure carbon dioxide, but in no change in the presence of nitrogen. Whereas partial pressures of oxygen, that is 5 parts with 95 parts nitrogen by volume, and 10 parts with 90 parts nitrogen, resulted in a decrease in virulence, with 20 parts oxygen and 80 parts nitrogen, the decrease was almost negligible. Media which under aerobic conditions failed to furnish suitable constituents for maintenance of virulence, that is spleen, aminoid peptone, powdered milk, beef infusion, whole rabbit, and rabbit muscle, also failed under nitrogen. Media from whole guinea pig kept the organism virulent for 246 transfers under nitrogen, but with some decrease. Media made from discard mice, survivors of pneumococcus infection, furnished conditions under nitrogen, which caused first a decrease of virulence, but later after 246 transfers, a restoration to a more virulent state. Gradual increase in temperature over a period of 10 days from 36.5°C. to 42°C. in a sample of medium, which was otherwise suitable for maintenance of virulence under aerobic conditions, resulted in a decrease in virulence.
CELLULAR REACTIONS IN THE MENINGES OF RABBITS TO TUBERCULO-LIPOID, PROTEIN, AND POLYSACCHARIDE, COMPARED WITH THE EFFECTS OF TUBERCLE BACILLI
Authors: Bickford J. Van Allen
Published: June 2004

1. Both living and dead tubercle bacilli, as well as tuberculophosphatide, give rise to lesions in which the same type of cell is found, a cell which may prove characteristic of the meningeal reaction. After the phosphatide this cell is produced by the phagocytosis of lipoidal material. The vacuoles of these cells are slowly broken into smaller and smaller size until they correspond to the type found in the epithelioid cells with coarse vacuoles. This change is much slower in the cells of the meninges than in the cells of the omentum and subcutaneous tissue.

2. Intrathecal injections of tuberculo-protein produce a characteristic rise in temperature in normal and tuberculous rabbits. Both normal and tuberculous rabbits, after repeated intrameningeal injections of a given dose of tuberculo-protein, may fail to give a rise in temperature and later react to a larger dose.
BODILY CHANGES AND DEVELOPMENT OF PULMONARY RESISTANCE IN RATS LIVING UNDER COMPRESSED AIR CONDITIONS
Authors: Smith F. J. C. , Heim J. W. , Thomson R. M. , Drinker C. K.
Published: June 2004

1. 244 albino rats from standard Wistar Institute stock have been kept for periods up to 72 days under the following conditions.

(a) Barometric pressure: 3040 mm. Hg. This means a partial pressure of oxygen of 635 mm. Hg and is equivalent to an 83.6 per cent oxygen mixture at normal barometric pressure.

(b) Temperature: 28°C.

(c) Humidity: 50 per cent relative.

(d) Rate of ventilation: 2660 liters per minute for all animals.

(e) Food and daily care were provided which induced normal growth in rats in the usual laboratory quarters.

2. The harmful factor in this environment was the increased oxygen tension. In our experiments the acute effects were active hyperemia and edema of the lungs, just as have been described by many investigators.

3. Only a small percentage of rats die from acute oxygen poisoning at the pressure employed. The majority return to good health objectively and survive several months of exposure.

4. Rats under 1 month of age display no clinical signs of acute oxygen poisoning, while in older animals the severity of the reaction and the mortality is directly proportional to the advance in age.

5. The symptoms of acute oxygen poisoning appear on the 3rd day of exposure in adults and reach maximum intensity during the 4th day, all deaths occurring at this time.

6. A continued weight loss is found in old rats, while the young gain weight, but not with normal vigor.

7. Adaptation to this toxic oxygen tension occurs in the albino rat during the first exposure, so that on reexposure acute oxygen poisoning does not develop.

8. Respiratory infection occurred sporadically in roughly 20 per cent of the normal adult rats in our laboratory colony. About the same incidence was found in the experimental rats during exposure; in most of these, chronic bronchiectasis and bronchopneumonia followed and proved fatal, indicating a lowered resistance in exposed animals.

9. Most rats exposed to an 80 per cent oxygen tension late in pregnancy have premature litters and die of acute oxygen poisoning, but if exposed early in pregnancy the majority survive.

10. Litters born during the first exposure of the mother are approximately 50 per cent underweight and die during the first 24 hours after birth.

11. A female, rendered resistant by a first exposure, produced a healthy litter during second exposure.

12. The continuous failure of adults to gain in weight and the fact that young animals grow slowly, together with the slowly progressing pulmonary pathology (11), indicate that high oxygen tensions not only produce acute changes in the lungs but also some alteration in the normal physiological processes, which may be termed "chronic oxygen poisoning."
STUDIES ON INFLAMMATION
Authors: Menkin Valy
Published: June 2004

A concentrated urea solution effectively dissolves fibrin.

The injection into the peritoneal cavity of a urea solution (30 or 50 per cent) together with or after an inflammatory irritant (aleuronat) prevents wholly or in part the local fixation of graphite particles or ferric chloride introduced subsequently. The histologic picture in the retrosternal lymphatics explains how this comes about. When free dissemination of graphite to the retrosternal nodes occurs, the lumen of the lymphatic vessel is unobstructed, whereas partial dissemination is accompanied by small fibrinous thrombi occluding the lumen in part only.

Trypan blue injected at the periphery of an inflamed skin area treated with a concentrated urea solution and bacteria (Staph. aureus) penetrates readily into the area, whereas it fails to do so when introduced around an inflamed area consequent on the injection of distilled water and bacteria (Staph. aureus).

Concentrated urea per se is an inflammatory irritant. Graphite particles injected into a peritoneal cavity previously treated with concentrated urea penetrate freely to the retrostemal lymphatic nodes; the lymphatic vessel is relatively unobstructed. Trypan blue injected into the circulating blood accumulates rapidly in cutaneous areas almost immediately after the latter have been treated with concentrations of urea ranging from 50 per cent down to 20 per cent.

The results of this study furnish evidence, in addition to that already provided, that fixation of foreign substances is primarily due to mechanical obstruction caused by a fibrin network and by thrombosed lymphatics at the site of inflammation. The significance of fixation in relation to immunity and its bearing upon some of the other processes involved in the inflammatory reaction have been stressed.
THE EFFECT OF LYMPHOCYTOSIS INDUCED WITH EMBRYONIC EXTRACT ON THE COURSE OF EXPERIMENTAL TUBERCULOSIS IN RABBITS
Authors: Smithburn Kenneth C.
Published: June 2004

1. Chick embryo extract given intravenously did not favorably influence the course of experimental tuberculosis in rabbits, although it did cause lymphocytosis and lymphoid hyperplasia.

2. The tuberculous animals treated with chick embryo extract showed lower values for hemoglobin and red blood cells than tuberculous controls inoculated from the same suspension.

3. Under the conditions of these experiments an increase in the number of young, immature cells in the lymph nodes was accompanied by more extensive tuberculous lesions in the lymph nodes and especially in the germinal centers of the nodes. A possible analogy to lymphatic tuberculosis in children is suggested.

4. The observations of previous investigators on the progression and later regression of lesions in experimental tuberculosis have been confirmed. The distribution, character, and extent of lesions have been studied and are presented in tabular form.

5. The presence and significance of tuberculous thrombi in the lungs are discussed.
THE DIPHASIC NATURE OF TUBERCULOSIS IN RABBITS AFTER INTRAVENOUS INOCULATION WITH BOVINE TUBERCLE BACILLI
Authors: Thomas R. M.
Published: June 2004

It has been shown that in a large group of rabbits inoculated intravenously with bovine tubercle bacilli the disease which follows resolves itself into two distinct phases. The first phase manifests itself in widespread diffuse lesions which subsequently regress. The mortality rate shows a rise and fall during this period, which have been correlated with the extent of lesions and with the changes in the blood cells. The duration of this phase is approximately 80 to 90 days. Following this period the mortality rate again rises and falls, during a period when all animals show lesions of a chronic nature. In an infected group the number of fatalities in the first phase is a function of the size of the dose. When the size of the dose and other conditions are held constant, a definite basis upon which to compare the reactions of treated animals is established.

Studies of the blood cells during the course of the disease show that the changes in these cells reflect the course of the lesions in the first phase when other signs are lacking and offer a valuable means of making an estimate of the state of resistance of the animal from time to time.

Studies of blood counts made on rabbits before their inoculation with tuberculosis were analyzed with regard to the relative longevity of the animals. It was found that those animals whose blood cells of various sorts deviated least from the modal value for the entire group survived longer than those animals whose counts were significantly high or low.
I. THE PERMEABILITY OF THE WALL OF THE LYMPHATIC CAPILLARY
Authors: Hudack Stephen , McMaster Philip D.
Published: June 2004

A technique has been developed for the demonstration of lymphatic capillaries in the ear of the mouse by means of vital dyes and for tests of their permeability under normal and pathological conditions. The lymphatics become visible as closed channels from which the dyes escape secondarily into the tissue. Some of them, cross-connections, with extremely narrow lumen, would seem ordinarily not to be utilized.

There is active flow along the lymphatics of the mouse ear under ordinary circumstances. The movement of dye was always toward the main collecting system. The valves of the lymphatics as well as fluid flow prevented distal spread. There was in addition slow migration, apparently interstitial in character, but in the same general direction, of dots of color produced by the local injection of dye.

The normal permeability of the lymphatics was studied with dyes of graded diffusibility. Their walls proved readily permeable for those highly diffusible pigments that the blood capillaries let through easily, but retained those that the latter retained. Finely particulate matter (India ink, "Hydrokollag"), they did not let pass. No gradient of permeability was observed to exist along them such as exists along the blood capillaries of certain organs.

The observed phenomena of lymphatic permeability, like those of the permeability of the blood capillaries, can be explained on the assumption that the lymphatic wall behaves like a semipermeable membrane.
THE DEGREE OF COMPENSATORY RENAL HYPERTROPHY FOLLOWING UNILATERAL NEPHRECTOMY
Authors: MacKay E. M. , MacKay L. L. , Addis T.
Published: June 2004

Compensatory hypertrophy of the kidney in albino rats becomes less as age advances. There is a rapid decrease from 5 days to 60 days of age and then a slow diminution throughout adult life.
THE PRODUCTION OF OSTEOGENIC SARCOMATA AND THE EFFECTS ON LYMPH NODES AND BONE MARROW OF INTRAVENOUS INJECTIONS OF RADIUM CHLORIDE AND MESOTHORIUM IN RABBITS
Authors: Sabin F. R. , Doan C. A. , Forkner C. E.
Published: June 2004

The observations in this work suggest that with certain doses of radioactive material, the fundamental damage in the lymphoid tissues is to the stem cell and that the damage is to the chromatin of the nuclei of these cells. The erythroid tissues are apparently less susceptible to radioactive material than the lymphoid tissues but an original anemia of secondary type from peripheral destruction may eventually be changed to one of primary type through decreased maturation of primitive cells in the marrow. The damage of lymph nodes and bone marrow leads to atrophy of these organs. The cells of the liver and thymus suffer nuclear damage of the same general character as is seen in the lymph nodes, and there is an atrophy of these organs.

The storage of the radioactive material in the bones gave rise to osteogenic sarcomata in two out of seven rabbits surviving from 11 to 19 months. A repetition of the experiment has been undertaken with more intensive studies to test the validity of the findings.
HISTOLOGICAL STUDIES ON HOG CHOLERA
Authors: Seifried O. , Cain C. B.
Published: June 2004

In cases of acute hog cholera the earliest and most pronounced lesions occur in the capillaries and smaller arteries. Larger arteries and veins are less frequently involved. The lesions consist of swelling and proliferation of endothelial cells together with retrogressive changes in them and in the other parts of the blood vessel walls.

The character and degree of these lesions seem to be dependent upon the virulence of the virus and, to some extent, upon the presence of secondarily invading bacteria. We believe that these lesions should be considered a principal feature of the histopathology of hog cholera.
HISTOLOGICAL STUDIES ON HOG CHOLERA
Authors: Seifried O. , Cain C. B.
Published: June 2004

1. The hemorrhages, foci of necrosis, and anemic infarcts met with in the various organs in virus hog cholera, result primarily from the vascular lesions described in a previous paper of this series. Although they are not dependent on the presence of secondarily invading bacteria, their severity is influenced by these organisms.

2. The lesions in the lymph nodes, spleen, kidneys, and central nervous system seem to be of special diagnostic value in questionable cases of hog cholera. The presence of an encephalitis alone does not justify the diagnosis of hog cholera because in the central nervous system of swine similar inflammatory lesions occur in other diseases.
THE INFLUENCE OF THE PLASMA COLLOIDS ON THE GRADIENT OF CAPILLARY PERMEABILITY
Authors: Smith Frederick , Dick Macdonald
Published: June 2004

The influence of osmotic conditions on the gradient of capillary permeability disclosed by the distribution into mammalian muscle of vital dyes has been tested experimentally. The percentage of circulating blood proteins was increased in rabbits by the injection of compatible plasma, or of compatible serum concentrate obtained by means of a new method of ultrafiltration which has proved both rapid and effective. It was found that when this had been done and the circulatory conditions had stabilized themselves, the gradient of capillary permeability still existed, though its effective extent was less than under normal circumstances. When the percentage of circulating blood proteins was reduced, on the other hand, by repeated bleedings with return of the cells, either as such or suspended in the protein-free fluid obtained by dialysis of serum, the extent of the gradient of capillary permeability was broadened and dye passed out into the tissue more readily than usual from the capillary as a whole. In contrast to these findings injection of a very hypertonic dextrose solution during the period when dye was escaping had no perceptible effect on the gradient of capillary permeability.

The observed phenomena cannot be explained by a flow of dye-stained fluid into or out of the blood vessels. The gradient of capillary permeability exists independently of osmotic conditions, though its extent can be markedly influenced by altering the amount of circulating blood proteins. A considerable proportion of the dye used to study the gradient is adsorbed upon these proteins, as subsidiary experiments have shown. This happening provides a sufficient cause for the differences observed in the extent of the gradient when the percentage of proteins is increased or diminished.

The evidence like that of previous papers indicates that the cause for the gradient is to be found in a structural differentiation along the capillary, such that the barrier offered by its wall progressively diminishes on the way to the venule. Most current estimates of the effective osmotic pressure of the blood proteins fail to take into account the existence of local differences in permeability along the capillary.
SEROLOGICAL REACTIONS WITH SIMPLE CHEMICAL COMPOUNDS (PRECIPITIN REACTIONS)
Authors: Landsteiner K. , van der Scheer J.
Published: June 2004

Experiments are described demonstrating the precipitation of azodyes by immune sera prepared by the injection of azoproteins containing the same azo component. These precipitin reactions prove conclusively the view already advanced on the basis of inhibition reactions that antibodies combine specifically with substances of small molecular weight. Although in this respect both phenomena have the same significance, the precipitin reactions with dyes are simpler in that the aid of a protein antigen is eliminated.

That specific serological precipitin reactions can take place with substances other than proteins has been amply demonstrated by studies on bacterial antigens (14) (polysaccharides (15)). The present findings show that for the precipitation with immune sera not even a high molecular weight of the reactive substance is required. Factors determining the tendency to separate out from the liquid upon combination with antibody seem to be the colloidal state of the solution and the chemical composition of the substance. With regard to the influence of chemical composition, a striking example is provided by the suberic acid dye which gives particularly strong precipitin reactions, most probably on account of its long aliphatic side chains.

The results reported may be of use for studies on the mechanism of serological precipitation.
THE INFLUENCE OF PLASMA PROTEIN ON THE CHLORIDE CONTENT OF THE CEREBROSPINAL FLUID
Authors: Coombs Herbert I. , Thompson Kenneth Wade
Published: June 2004

1. When the plasma protein of dogs is lowered by plasmapheresis, the concentration of chloride and sodium in the plasma and the cerebrospinal fluid tends to become the same, a diminishing of the usual disparity which exists in the presence of a normal plasma protein.

2. This is in accord with the theory that the cerebrospinal fluid is a dialysate, with the choroid plexus acting as a simple dialyzing membrane.