bluuebunny/crossref_metadata_2025 huggingface dataset:
OBSERVATIONS ON RESISTANCE TO THE FLOW OF BLOOD TO AND FROM THE LUNGS
Authors: Moore Richmond L. , Binger Carl A. L.
Published: June 2004

1. Embolism of pulmonary arterioles and capillaries produced by the intravenous injection of starch grains results in a dilatation of the pulmonary artery and the right chambers of the heart. This has been demonstrated both by x-ray studies and direct inspection.

2. The dilatation of the pulmonary artery and heart occurs synchronously with the acceleration of respirations.

3. Dilatation of these structures produced by other means, such as obstruction to the flow of blood to and from the lungs, by gradually clamping either the pulmonary artery (cat and dog) or pulmonary veins (cat) does not, however, give rise to rapid and shallow breathing.

4. The effect of these maneuvers on respiration does not become apparent until respirations suddenly cease.

5. Neither does sudden restriction of the pulmonary vascular bed by clamping the left branch of the pulmonary artery give rise to rapid and shallow breathing, though this procedure may cause an increase in CO2 tension and in hydrogen ion concentration of the blood.

6. Since rapid and shallow breathing is not the result of (1) anoxemia, (2) increased pCO2 and hydrogen ion concentration of the serum, (3) restriction of pulmonary vascular bed by nearly half, (4) increase in resistance to the flow of blood to and from the lungs) (5) the presence of starch grains in the lungs acting as a local irritant, it must be the result of the secondary pathological changes which occur in the pulmonary parenchyma following embolism.

7. The nature of these changes, congestion and edema, has been discussed elsewhere. Whether they operate directly on nerve endings or through their influence on lung volume and tissue elasticity is not certain.

8. Various important clinical analogies have been emphasized.
EXPERIMENTAL BONE MARROW REACTIONS
Authors: Muller Gulli Lindh
Published: June 2004

1. The effect produced by intravenous administration of gum shellac solution varied directly with the strength of the solution and the amount injected.

(a) Strong solutions were intensely toxic and fatal to all the animals injected. Toxicity was abolished by the presence of carbon particles in the solution.

(b) Medium strength solutions produced a marked normoblastosis followed by an erythroblastosis if injections were continued, accompanied either by an initial rise of red blood cells and hemoglobin followed by a decrease or an initial decline followed by an increase. The decrease of erythrocytes and hemoglobin did not amount to an actual anemia, and was usually concomitant with the greatest outpouring of nucleated red cells.

(c) Small doses elicited the same kind of response except that the normoblastosis was less marked, the decrease of red cells and hemoglobin minimal or absent, the increase of red blood cells and hemoglobin marked in most instances.

(d) Minimal doses elicited no appreciable reaction.

2. The bone marrow in animals killed after a course of injections showed intense erythrocytic hyperplasia. This disappeared after a variable length of time with a return of the bone marrow to apparently normal condition.

3. Toxic effects with non-fatal doses in form of hemorrhages were produced mainly in the bone marrow and occasionally in the kidney under the following conditions.

(a) After one injection in an animal with hyperplastic marrow (hemorrhages ih the bone marrow only).

(b) After the fourth and fifth dose when administered at long intervals (4 to 19 day intervals).

(c) After one injection given 40 days after several successive injections (one animal only).

4. Small and divided doses administered at long intervals produced no apparent ill effect.

5. Subcutaneous administrations did not elicit any marked systemic reactions. Locally there was induration and edema.

6. The conclusion was drawn that gum shellac solution stimulates markedly the production of erythrocytes in the bone marrow. The mechanism of stimulation is not clear, but it seems unlikely that it is due to destruction of red blood cells in the peripheral blood stream.
THE OCCURRENCE OF DEGRADED PNEUMOCOCCI IN VIVO
Authors: Reimann Hobart A.
Published: June 2004

It is conceivable that a change from the virulent, non-phagocytable S form of Pneumococcus to the avirulent phagocytable R form may take place in pneumococcus disease, but the experiments here reported do not settle the question whether or not this is an important factor in determining the outcome in natural infection. It has been shown experimentally that the degradation from the S form to the R form actually does take place in cultures of Pneumococcus growing in agar subcutaneously embedded in guinea pigs, in agar enclosed in vials subcutaneously embedded in rabbits, and spontaneously in the blood stream of infected horses. However, it was not possible in any of the experiments here cited to demonstrate the complete change from S to R pneumococci before the bacteria disappeared from the body. When the intermediate or R forms did appear, they were always accompanied and usually exceeded in number by the S forms and all three forms disappeared together. S organisms may disappear entirely without evidence of first going through the intermediate and R stages. On the other hand, contrary to expectations, pure cultures of R forms remained viable in subcutaneous foci for weeks although apparently freely accessible to the action of phagocytes. It seems of some significance that the R forms appeared early in the vials (inoculated with S pneumococci) in immunized and normal rabbits alike, indicating that the presence of demonstrable specific immune bodies was not alone responsible for the variation of the bacteria.

Of some importance also is the fact that R forms were never derived from similarly prepared control cultures growing in vitro at the same temperature and immersed in normal serum, although the S forms remained viable and unaltered for 6 weeks. It is likely that variations of pneumococci do not occur readily when S cultures are exposed to normal serum in vitro, especially when growing in closed vials under a diminished oxygen supply, for it has previously been shown (2) that only slight variation occurs even after prolonged (240) transfers in heterologous serum broth in the test-tube. It is possible, therefore, that the variation which occurred among pneumococci growing in agar vials embedded in normal rabbits was actually provoked by unknown influences in the living tissue fluids.

Although R forms have been shown to occur in vivo, no positive evidence can be derived from these experiments to prove that recovery from pneumococcus infection depends upon the degradation of the virulent S forms of pneumococci to the avirulent R forms and the subsequent destruction of the latter by phagocytes.
STUDIES ON THE PHYSICAL AND CHEMICAL PROPERTIES OF THE VIRUS OF FOOT-AND-MOUTH DISEASE
Authors: Olitsky Peter K. , Boëz Louis
Published: June 2004

The virus of foot-and-mouth disease exhibits a remarkable resistance to such bactericidal agents as the narcotic solvents (alcohol, ether, chloroform), or such antiseptics as phenol, bichloride of mercury, or cresol, as shown by tests made by others and ourselves. We have shown, however, that the resistance of the incitant to these chemicals is really masked. It is due to the fact that the reagents coagulate the proteins of the medium in which the virus is, as a rule, suspended. As a result the active agent is protected by the coagula which prevents direct contact with the chemicals. On the other hand, if advantage is taken of the periodic phenomenon attending such processes, and coagulation is prevented, the virus can then be brought under direct action of the antiseptics. Under these conditions, the incitant is more sensitive to destruction by the chemicals than is the living staphylococcus. As a corollary, the virus is destroyed as rapidly, or even more so, than are staphylococci by substances such as sodium hydrate (1 to 2 per cent solutions), or antiformin (1 per cent solution) which do not form coagula. We are therefore compelled to contradict the opinion that the extraordinary resistance to certain chemicals of the virus of foot-and-mouth disease, as it ordinarily occurs admixed with proteins, is an indication of its inanimate character.

The results of a large series of experiments lead to the conclusion that of a number of antiseptics employed the sodium hydrate in 1 to 2 per cent solutions is an effective virucide. It is capable of killing the virus within 1 minute as shown by tests on cattle and guinea pigs. Furthermore, its effectiveness is not diminished even when the virulent material is admixed with cattle's urine, with manure, or with garden soil. The experimental evidence and the cheapness suggest its use in field practice as a disinfectant.
STUDIES ON THE PHYSICAL AND CHEMICAL PROPERTIES OF THE VIRUS OF FOOT-AND-MOUTH DISEASE
Authors: Olitsky Peter K. , Boëz Louis
Published: June 2004

No multiplication of the virus in vitro was observed. We have found, however, that the optimum conditions necessary for the preservation of the virus in artificial media are as follows:

The hydrogen ion concentration of the medium should be 7.5 to 7.6, not only at the beginning, but, and more important, at the conclusion of the period of observation. A strict anaerobic atmosphere is also favorable, as is a temperature below 37°C. A semisolid structure of the medium appears to be advantageous and this can be effected by the use of ¼th per cent agar or 10 per cent gelatin. Of the two, the gelatin is more desirable, and of the latter the most effective material is gelatin from which the impurities have been most thoroughly removed, namely the gelatin employed by Loeb for his isoelectric determinations. This material is best adjusted to the proper hydrogen ion concentration (7.5–7.6) with potassium hydroxide and not with buffer phosphate.

Gelatin is the simplest of protein media available and its employment is in keeping with the principle we have found that the requirements for life of the virus of foot-and-mouth disease are of the simplest. The addition of organic or complex protein substances, such as dextrose, broth, serum, lipoids, etc., to a simple basic medium interferes with the effectiveness of the latter. It is thus not surprising that we were unable to confirm the cultural results of Frosch and Dahmen for neither their medium nor its components or their method satisfies the essential conditions necessary to maintain artificially the life of the virus.

Furthermore, from the standpoint of technique it was found necessary when comparing 2 or more media for their value in preserving the incitant, to employ all of them in a parallel experiment with the same sample of virus, for the factors of potency of the active agent, contamination, and changes in hydrogen ion concentration, if variable, may give rise to faulty interpretations. Moreover, activity in 3 successive subplants may be regarded as mere preservation but not multiplication of the virus.

Finally, we discuss the status of the virus from the point of view of its fluid or particulate, and its animate or inanimate, characters.
OXYGEN POISONING IN MAMMALS
Authors: Binger Carl A. L. , Faulkner James M. , Moore Richmond L.
Published: June 2004

1. Oxygen in concentrations of over 70 per cent of an atmosphere is poisonous to dogs, rabbits, guinea pigs and mice.

2. The poisonous effects manifest themselves in drowsiness, anorexia, loss of weight, increasing dyspnea, cyanosis and death from oxygen want.

3. The cause of oxygen want is a destructive lesion of the lungs.

4. The lesion may be characterized grossly as an hemorrhagic edema. Microscopically there is to be seen in varying degrees of intensity (a) capillary engorgement with hemorrhage, (b) the presence of interstitial and intraalveolar serum, (c) hypertrophy and desquamation of alveolar cells, (d) interstitial and alveolar infiltration of mononuclear cells.

5. The type of tissue reaction is not characteristic of an infectious process and no organisms have been recovered at autopsy from the heart's blood or from lung puncture.

6. The poisonous effects of inhalations of oxygen-rich mixtures do not appear to be related to impurities in the oxygen, nor are they related to faulty ventilation, excessive moisture or increased carbon dioxide in the atmosphere of the chambers in which the experimental animals were confined.
STUDIES ON THE BACTERIOPHAGE OF D'HERELLE
Authors: Bronfenbrenner J. , Muckenfuss R.
Published: June 2004

We have been able to confirm the observations of Twort as well as of Gratia, that dead staphylococcus may undergo lysis if, in addition to a suitable bacteriophage, there is also present live staphylococcus. Moreover, we have endeavored to ascertain the mechanism of this phenomenon and have found that in order to elicit it it is necessary to control the numbers of live and dead bacteria in the mixture. An excess of dead bacteria interferes with lysis by adsorbing the bacteriophage before it has the opportunity to initiate necessary changes in the live bacteria, so that all lysis is prevented. The phenomenon is specific, that is, the lysis of live bacteria is accompanied by lysis of dead bacteria of the same species only. Lysis of dead bacteria occurs best with staphylococcus, an organism which easily undergoes spontaneous autolysis under appropriate conditions. In the case of B. coli or B. dysenteriæ the lysis of the dead bacteria is uncertain. Dead bacteria need not be present in the mixture at the beginning of the experiment; they will be dissolved if added any time before, during, or after the completion of lysis of live bacteria.

If the test is performed so that a suitable semipermeable membrane is interposed between the dead and live bacteria, the dead bacteria are not dissolved, in spite of the lysis of live bacteria on the other side of the membrane. The agent determining the lysis of dead bacteria is not diffusible, while the principle initiating the lysis of live bacteria diffuses freely and is demonstrably present on both sides of the membrane. The complete independence of the agent causing dissolution of dead bacteria from bacteriophage can also be shown by separating the two agents by means of filtration, or by adsorption on bacteria.

The ferment-like substance responsible for the lysis of dead bacteria is different from the bacteriophage. It is not diffusible through collodion, it is easily adsorbed on clay filters, it is heat-labile, and is inactivated on standing.

An agent possessing identical properties was found in cultures of staphylococcus undergoing spontaneous autolysis in the absence of bacteriophage, but in this instance the agent appeared in the filtrates considerably later than it did when phage was present.
BACTERIUM LEPISEPTICUM INFECTION
Authors: Webster Leslie T. , Burn Caspar
Published: June 2004

In this paper we have attempted to describe the manner of spread of an endemic, native, respiratory infection and a method for its control. The essential factor determining the prevalence of such an endemic disease is, we believe, host susceptibility, which is controlled by hereditary and environmental influences. Furthermore, it seems probable that the amount of this population susceptibility determines the dosage of specific microbes available to the population.

An increase in dosage in the herd is followed by an increase in the spread and severity of the infection, and a decrease by a corresponding alleviation. Hence, two methods for the prevention of epidemics are available: (1) an enhancement of population resistance, and (2) the reduction to a minimum of available dosage. These procedures have proved successful for 3 years in maintaining a population of breeding rabbits, in the midst of a badly infected community, entirely free from Bact. lepisepticum infection.

Confirmation of the above conclusions has been gained from other studies in the field of experimental epidemiology. Dr. D. T. Smith (2), at Saranac, New York, found that changes in population susceptibility were responsible for a severe outbreak of Bact. lepisepticum infection and septicemia. Freund (3), at Berlin, has just published an interesting account of respiratory epidemics of rabbits and guinea pigs, apparently brought about by sudden changes in temperature and housing conditions. Pneumonia and Pasteurella infection, endemic in the population, increased suddenly in extent and severity. Nevertheless, neither endemic nor epidemic strains of the microorganisms were found to be especially virulent. Dr. Theobald Smith (4), in a study of paratyphoid epidemics of guinea pigs, has made similar observations. He noted that pregnant females acted as the foci of infection, and that from these individuals, presumably of lessened resistance, the bacteria were given off and infection was spread.

The studies in experimental epidemiology are rapidly reaching a stage where they may be applied to the problems of human disease. Indeed, more recent observations of the mode of spread of pneumonia (5–7), scarlet fever (8), typhoid (9, 10), plague (11), diphtheria (12–14), measles (15), and tuberculosis (16–18) increasingly show a tendency to discard the theory of fluctuating microbic virulence and to emphasize the importance of the host factors.
THE ACTION OF THE SYMPATHETIC UPON THE EXCITATORY PROCESS IN THE MAMMALIAN HEART
Authors: Andrus E. Cowles , Martin Louis E.
Published: June 2004

Stimulation of the sympathetic nerve endings, after paralysis of the vagus, accelerates the transmission of the excitatory process in the dog's auricle.

Following the functional exclusion of the vagus ergotamine slows the rate of the sinus rhythm, depresses A-V conduction, and delays the transmission of the excitatory process in the auricle.

The relation of the sympathetic and parasympathetic nerves in the control of the cardiac rhythm is discussed.
ON THE INFLUENCE OF ACID GROUPS ON THE SEROLOGICAL SPECIFICITY OF AZOPROTEINS
Authors: Landsteiner K. , van der Scheer J.
Published: June 2004

The method of partial synthesis of antigens as employed in the foregoing experiments obviously cannot be substituted for the chemical study of natural antigens. But some questions of a rather general nature not easily accessible to investigations of the latter sort, may be approached by the use of artificial protein compounds. Thus the results reported indicate a peculiarity of certain chemical structures such as acid radicals.

The group of immune sera obtained by injecting azoproteins made from non-acid azo components had a wide range of activity. Substituents like CH3, OCH3, NO2, Cl, Br, I, in the aromatic nucleus altered the reactions to a moderate degree only, in most cases. The effects were dependent more on the position than on the nature of the substituents. Two substances were found, however, which had a pronounced effect on the specificity of the compound protein, namely acetyl-para-phenylenediamine and para-aminoacetophenone. In consideration of the above facts it is uncertain whether the antigenic changes noticed by Obermayer and Pick (7) after treating proteins with nitric acid, nitrous acid or iodine are mainly due to the substitution of hydrogen in the benzene ring by NO2 and I, as is the general belief, or to other changes of the protein. This question had been raised already by the observation that the proteins treated with HNO3 or HNO2 containing respectively the nitro or the diazo group, did not differ substantially in their serological properties (8).

The antigens made from acid compounds form a group with distinctive features. In the first place the presence of acid radicals destroys the reactivity with the immune sera for the non-acid substances. This influence is so marked that even the reaction with the species specific part of the protein, if such is present, appears to be diminished. Also the sera produced with the acid antigens react but feebly with the non-acid azoproteins. Accordingly it was possible to show that by hydrolysis of the ester of an aromatic acid contained in an azoprotein the serological reactions of the antigen underwent a radical change.

The presence of a free carboxyl group in the antigens not only determines the characteristics mentioned but there is reason to believe that it increases markedly the degree of specificity exhibited by the antigens and the corresponding immune sera, when cross-tests are made with a number of acid azoproteins and their antisera. This is brought out by a comparison of the results of the present investigation with those described previously (3). It is of interest in this respect that the specific carbohydrates found by Avery and Heidelberger in pneumococci and pneumobacilli are mostly, if not in all cases, compounds of distinctly acid character.
THE DEVELOPMENT OF AGGLUTININS AND PROTECTIVE ANTIBODIES IN RABBITS FOLLOWING INHALATION OF PNEUMOCOCCI
Authors: Stillman Ernest G.
Published: June 2004

1. Following repeated inhalations of Type I pneumococci agglutinins and protective antibodies can be demonstrated in the serum of rabbits.

2. The percentage of rabbits whose serum shows agglutinins remains stationary after the 5th exposure, but the percentage of rabbits showing protective antibodies in their sera steadily rises.
PHYSICAL, CHEMICAL, AND BIOLOGICAL STUDIES ON THE VIRUS OF VESICULAR STOMATITIS OF HORSES
Authors: Olitsky Peter K.
Published: June 2004

A taxonomic study of the virus of vesicular stomatitis is presented along with evidence additional to that already reported1 to show the similarity of this virus to that of foot-and-mouth disease. The connection of the two is discussed and the deduction drawn that their generic relationship is close. On the contrary, the differences between these two viruses and the herpetic are sufficiently marked to indicate a lack of generic connection among the three.

The results of a comparative study on the effects of particular wave-lengths and energies of monochromatic ultra-violet light on the virus and on Staphylococcus aureus reveal that the adsorption of specific energies by the two is parallel. Since the adsorption of specific energies is an index of chemical character, these experiments suggest that the virus is similar in character and chemical constitution to bacterial protoplasm.
SURFACE TENSION OF SERUM
Authors: du Noüy P. Lecomte
Published: June 2004

Experiments are reported which indicate that a shift toward higher concentrations is observed in the minimum value of the static surface tension when plasma instead of serum solutions is used. The amount of the shift, expressed as a function of the concentration, shows that the figures are in satisfactory agreement with the determined amount of fibrinogen in the plasma.

Some evidence is given that "plasma molecules" capable of organizing themselves on adsorbing surfaces exist in plasma, and that their length would be approximately 4.3 mµin round figures,instead of 4.0 mµ for the serum. The area occupied in the plane of adsorption by one individual molecule is, however, smaller than that occupied by the "serum molecule," thus indicating a marked structural difference between the two, the "plasma molecule" being narrower but longer than the "serum molecule." This difference may be due either to a different orientation accompanied by an increase in one of the dimensions, or else to an actual difference in structure with respect to the main axis, resulting in a decrease in the mean diameter of the "serum molecule" with an increase in the length of its main axis. The mass of the "plasma molecule" is about 6.3 per cent larger than that of the "serum molecule, " in the case of rabbit serum.
THE SURFACE COMPOSITION OF THE TUBERCLE BACILLUS AND OTHER ACID-FAST BACTERIA
Authors: Mudd Stuart , Mudd Emily B. H.
Published: June 2004

Acid-fast bacteria in the boundary surface between salt solution and a test oil (tricaprylin) are spontaneously wet and enveloped by the oil. This behavior contrasts with that of all other cells studied by the interfacial tension method.

Four strains of human tubercle bacillus and an atypical bovine strain are an exception to the first statement above. These have possessed stability in the saline-oil interface; this stability is slight, however, and not comparable with that of non-acid-fast bacteria.

Acid-fast bacteria subjected to prolonged extraction with alcohol show resistance to wetting by oil comparable to that of non-acid-fast bacteria. These "defatted" bacteria nevertheless retain their acid-fast staining properties. Acid fastness cannot then depend on the integrity of a surface membrane.

Study of the cataphoresis of acid-fast bacteria by Freund has rendered the presence of protein in the surface highly probable. We are forced then to regard the surface of acid-fast bacteria as complex, containing at least lipoid and protein. Not improbably also carbohydrate is present.
CELL RESPIRATION STUDIES
Authors: Daland Geneva A. , Isaacs Raphael
Published: June 2004

1. The oxygen consumption of blood of normal individuals, when the hemoglobin is saturated with oxygen, is practically zero within the limits of experimental error of the microspirometer used.

2. The oxygen consumed in a microspirometer by the blood of patients with chronic myelogenous leucemia with a high white blood cell count, and of one with leucocytosis from sepsis, was proportional to the number of adult polymorphonuclear neutrophils in the blood.

3. No correlation could be made between the rate of oxygen absorption and the total number of white blood cells in the blood, or the total number of immature cells, or the number of red blood cells, or the amount of oxyhemoglobin.

4. The blood of patients with chronic myelogenous leucemia continued to use oxygen in the microspirometer longer than that of normal individuals, and the hemoglobin, in the leucemic bloods, became desaturated even though exposed to air.

5. In blood in which the bulk. of the cells were immature and the mature cells few, the oxygen consumption was lower than in blood in which the mature cells predominated. The rate of oxygen consumption of the immature cells was relatively low as compared to the mature.

6. The slower rate of oxygen absorption by the immature leucocytes in chronic myelogenous leucemia as compared to the mature cells, places them, in accord with Warburg's reports, in the class of the malignant tissues in this respect rather than in the group of young or embryonic cells.
EFFECT OF HOST IMMUNITY TO A FILTERABLE VIRUS (VIRUS III) ON THE GROWTH AND MALIGNANCY OF A TRANSPLANTABLE RABBIT NEOPLASM
Authors: Pearce Louise , Rivers Thomas M.
Published: June 2004

Experiments are reported in which were studied the course and character of a transplantable malignant neoplasm in normal rabbits and in rabbits immunized with a filterable virus, Virus III.

The disease which developed in immunized rabbits was extremely mild and much less severe than in normal animals.

The effect upon the tumor process displayed by Virus III immune rabbits in the direction of diminished malignancy is considered to be entirely non-specific in character, and the suggestion is made that it is accomplished through a more effective resistance of the host.
STUDIES IN EXPERIMENTAL EXTRACORPOREAL THROMBOSIS
Authors: Rowntree Leonard G. , Shionoya Takuji
Published: June 2004

A new method has been described for the study in vivo of thrombus formation in blood circulating extracorporeally in an artificial loop. This method permits of control of many factors, and hence of intensive study of thrombus formation under many and varied conditions. It admits of separate study of the formation of white thrombi and of the deposition of fibrin, which may apparently be independent processes.
STUDIES IN EXPERIMENTAL SYPHILIS
Authors: Chesney Alan M. , Halley Charles R. L. , Kemp Jarold E.
Published: June 2004

Syphilitic rabbits, whether untreated or treated after the 90th day of infection, were found to be more refractory to subsequent inoculation with the homologous strain of Treponema pallidum than to inoculation with heterologous strains of the same organism, when clinical criteria alone were employed in judging the outcome of reinoculation. The incidence of second infection with homologous strains was 5.4 per cent, as against 50 per cent with heterologous strains.2 The resistance which develops in rabbits during the course of a syphilitic infection appears therefore to be strain-specific rather than species-specific. The protection afforded against homologous strains was found to persist for at least as long as 6 months after treatment was discontinued.

A given strain may afford a higher degree of protection against some strains than against others, but whether this is to be explained upon the basis of biologic relationship or of differences in virulence, or possibly as the result of both of these factors was not disclosed by the experiments. Rabbits infected with a strain (Nichols) which had been adapted to this species for over a decade could be infected with strains which had been recovered recently from the human body. The previous existence of a syphilitic lesion in the testis which was used as the site for reinoculation did not seem to exert any influence upon the incidence of successful second infections obtained with heterologous strains of Treponema pallidum. Sometimes the course of the second infection produced by inoculation with heterologous strains was less pronounced than that observed in the controls, but in most instances no significant alteration was observed.

In syphilitic rabbits treated late in the course of the disease and reinoculated with heterologous strains of Treponema pallidum no lesion may develop at the site of reinoculation but nevertheless the Wassermann reaction may become positive and remain so for weeks thereafter. It is suggested that such animals may be examples of asymptomatic reinfection.
STUDIES ON PNEUMOCOCCUS GROWTH INHIBITION
Authors: Robertson Oswald H. , Sia Richard H. P.
Published: June 2004

A study was made of the pneumococcidal action of serum-leucocyte mixtures of pneumococcus-resistant animals with a view to determining whether this property of the blood is to be accounted for by the presence of certain serum constituents or by cellular characteristics which are lacking in the blood of susceptible animals. By means of a method specially developed for this purpose, it was found that, after adequate contact with the serum of pneumococcus-resistant animals, virulent pneumococci were phagocyted actively not only by the homologous leucocytes but also by the leucocytes of other resistant and susceptible animals. On the other hand, pneumococci exposed to the action of the serum of pneumococcus-susceptible animals were not taken up by the leucocytes of either the resistant or susceptible species. All the resistant animals tested, dog, cat, sheep, pig and horse, showed marked opsonic properties in their blood serum which were not found in the serum of susceptible ones, rabbit, guinea pig and human. There appeared, however, to be no essential difference in the phagocytic activity of the leucocytes from the various animals.

It was then shown that the pneumococcus-destroying power of serum-leucocyte mixtures was entirely abolished when heated serum was substituted for fresh serum and that such heated serum had lost much of its opsonic potency. Neither the living leucocytes alone nor extracts of the leucocytes were observed to exert any killing action on pneumococci. Further evidence of the controlling influence of opsonic action in the antipneumococcus defence mechanism of the blood, and its importance in natural resistance, was afforded by a study of the opsonin content and leucocytic functions of the blood of full grown and young rabbits as related to their widely varying degrees of pneumococcus susceptibility.
LOCAL SPECIFIC THERAPY OF EXPERIMENTAL PNEUMOCOCCAL MENINGITIS
Authors: Stewart Fred W.
Published: June 2004

1. Extensive acute, fibrinopurulent meningitis may be produced in dogs by the intracisternal injection of virulent Type I pneumococci.

2. Given an equal number of virulent infecting organisms, the rate of establishment of infection depends upon the phase of growth and the quantitative growth per cc. of culture plus an uncontrollable individual factor in the animal.

3. The pathology of pneumococcal meningitis is discussed. It resembles very closely the similar disease in man.

4. Systematic lavage and treatment with optochin-serum mixtures by the method of quadruple puncture, as described above, have resulted in cures of Type I pneumococcal meningitis in dogs.

5. The important factor in obtaining cures is to bring all regions of the meninges into frequent contact with the therapeutic agent.

6. In the absence of such contact, incomplete sterilization results and "reinfection" is almost inevitable.

7. Protocols show the necessity of repeated negative cisternal fluids, both on smear and on culture, before sterilization can be assured.

8. Recovered dogs subjected to meningeal reinfection show some degree of resistance.
THE SYSTOLIC BLOOD PRESSURE OF THE NORMAL RABBIT MEASURED BY A SLIGHTLY MODIFIED VAN LEERSUM METHOD
Authors: Dominguez R.
Published: June 2004

The blood pressure and pulse rate of 90 normal rabbits have been studied for various periods of time, from 1 day (accidental death interrupting the observation) to 15 months. The main data are presented in a table containing the blood pressure and pulse rate on the 1st day of observation, the maximum and minimum of both during the entire period of observation of each animal, together with the sex and weight of the animal. Separate tables are given showing the distribution of blood pressure, pulse rate and the "maximum" blood pressure by animals. Detailed data on two animals observed for the longest time are given in tabular form. The anatomical changes that occur in some carotids enclosed in a loop are described and discussed. Considerations on "excitement" and pathological conditions which arise spontaneously in rabbits are given. A criterion for a pathologically high blood pressure in rabbits is proposed.

The blood pressure of the normal rabbit ranges between 70 and 170 mm. Hg. The pulse rate, taken simultaneously with the blood pressure, fluctuates between 112 and 300 per minute.
STUDIES ON THE BIOLOGY OF STREPTOCOCCUS
Authors: Dochez A. R. , Stevens Franklin A.
Published: June 2004

Rabbits immunized with filtrates of cultures of hemolytic streptococcus from erysipelas show cutaneous allergy. Two periods of allergy have been observed, an early and a late phase. The earliest reactions occurring in the first period of allergy can be neutralized with erysipelas immune sera.

The rash of scarlet fever and the Dick reaction are apparently allergic reactions to products of Streptococcus scarlatinæ.
THE RHYTHMIC RANGE OF THE WHITE BLOOD CELLS IN HUMAN, PATHOLOGICAL LEUCOPENIC AND LEUCOCYTIC STATES, WITH A STUDY OF THIRTY-TWO HUMAN BONE MARROWS
Authors: Doan Charles A. , Zerfas Leon G.
Published: June 2004

In a study of twenty clinical cases with a wide range of diagnoses, repeated total counts of the white cells at 15 minute intervals reveal a large fluctuation at various levels comparable to that found for the normal (1, 2). The granulocytes seem to follow a more or less hourly rhythm, the most marked shift to the left in the Ameth pattern and the moment of greatest percentage of motility coinciding with the peaks.

The independence found existing between the peripheral blood concentrations of individual strains of white cells and the red cells, as determined by total and differential counts, their differential response to pathological and pharmacological stimuli, and their normal relative relations, all indicate some separate physiological mechanism of control for each type of cell, either working through, or independently of, their sources of origin.

The many factors to which the circulation of the blood, as such, is subject, the complexity of the influences on origin, maturation, delivery, longevity, and destruction of each cell group, the limitations inherent in the present involved, indirect technics of counting, combine to make any single observation subject to grave misinterpretation. The value to the clinician must come in repeated observations, at times when the diagnosis or a therapeutic procedure is in doubt, at frequent intervals, at other times over longer or shorter periods, but always with the relation between consecutive counts, rather than the absolute values, the important point for consideration.

Both the red and the white cells probably change their relative concentrations in the peripheral blood from time to time over a considerable range that is quite within normal physiological limits, so that, in theoretical considerations and in practical functional estimations, a zonal concept with adequate individual extremes should always be kept in mind for both physiological and pathological states.

A cytological analysis of thirty-two bone marrows from human biopsy and autopsy material shows the striking reciprocity found to exist between the myelocytes and the mature polymorphonuclear leucocytes. This, together with the observed focal uniformity of maturation found in bone marrow, and the periodicity of the fluctuations of the neutrophils in the peripheral blood, leads to the formulation of the hypothesis of a constant functional withdrawal of granulocytes from the peripheral blood with a periodic delivery of new cells from the marrow, which in leucopenia and in leucocytosis represents a depression or a stimulation, respectively, of the normal mechanism. The nature and degree of the response are an approximate index of the cellular factor in the complex of the "resistance" of the particular individual.
MICROBIC VIRULENCE AND HOST SUSCEPTIBILITY IN PARATYPHOID-ENTERITIDIS INFECTION OF WHITE MICE
Authors: Pritchett Ida W.
Published: June 2004

When 5 per cent of butter fat or cod liver oil is added to a bread and milk diet, in itself adequate to promote the breeding and rearing of a healthy stock of mice through a period of years, the resistance of these mice to per os infection with the paratyphoid mouse typhoid bacillus (B. pestis caviæ), as compared to that of mice on the unmodified diet, is definitely increased. A similar effect may be obtained with a McCollum "complete" diet, even when the butter fat is omitted, and with a bread and milk diet in which the milk used has been rayed with a mercury vapor lamp. When an inactive fat like Crisco is added to the bread and milk diet, the results obtained are not very clear-cut. While seasonal fluctuations in resistance to mouse typhoid were not completely eliminated by the various modified diets, they were nevertheless reduced, the modified diets tending to stabilize the death rate at a point lower than that usually reached by the mice on the control diet.
AN EXPERIMENTAL STUDY OF DIATHERMY
Authors: Binger Carl A. L. , Christie Ronald V.
Published: June 2004

1. Prevention of the access of air to one lung, while its circulation is intact, results in little, if any, change in the rate of heating of the lung by the diathermy current.

2. Occlusion of a main branch of the pulmonary artery during the flow of the current results in a sudden rise in temperature in the lung whose artery has been occluded, with subsequent heating, however, at the original rate. Under these circumstances death of the animal is accompanied by a precipitous rise in the temperature of both lungs.

3. When the pulmonary veins as well as the artery to one lung are ligated the circulation through the bronchial vessels is also stopped. Diathermy then results in a local rise in temperature in the lung equivalent to that seen in the other lung after death.
THE SOLUBLE SPECIFIC SUBSTANCE OF FRIEDLÄNDER'S BACILLUS
Authors: Goebel Walther F. , Avery Oswald T.
Published: June 2004

1. Methods are given for the isolation of specifically reacting nitrogen-free polysaccharides from Type A and Type C Friedländer's bacillus.

2. The properties of these specific carbohydrates have been outlined.
A STUDY OF THE PERIVASCULAR TISSUES OF THE CENTRAL NERVOUS SYSTEM, WITH THE SUPRAVITAL TECHNIQUE
Authors: Kubie Lawrence S.
Published: June 2004

1. The presence of clasmatocytes in the adventitial sheath of the blood vessels of the normal brain has been shown. Thus far, these are the only mesodermal phagocytes, the presence of which in the central nervous system has proven to be demonstrable by the supravital technique.

2. The clasmatocytes are vacuolated even normally.

3. The vacuolation increases in the clasmatocytes of the whole brain as result of a localized injury, and it increases also throughout the central nervous system in the early stages of an herpetic encephalitis, even before gross damage to nerve cells or myelin can be demonstrated.

4. The endothelial cells of blood vessels have not exhibited any signs of multiplication or of vacuolation. They have not apparently given rise to any of these phagocytes, nor taken any part in the phagocytic reaction themselves.

5. Along capillaries, the phagocytic cells are seen only rarely, and it is possible that they have wandered along these vessels from the nearby venules and arterioles.

6. Trypan blue, injected without pressure into the subarachnoid space, finds its way rapidly down the perivascular sheath and enters the clasmatocytes of the sheath, deep within the substance of the brain. From this fact may be deduced the functional patency of the perivascular channels and their continuity with the subarachnoid space.

7. Lymphocytes are seen normally in the perivascular sheath, and the presence of the large young forms along with the intermediate and the small old cells suggests that they develop in this situation and give rise to the lymphocytes of the cerebrospinal fluid by wandering out into the subarachnoid space.

8. In response to an herpetic encephalitis, as well as other injury, a huge increase in the number of lymphocytes and of clasmatocytes occurs in the perivascular tissues.

9. The multiplication of both cell types seems to begin simultaneously, but never at the same spot, any one point along a vessel exhibiting a marked preponderance of either one form or the other.

10. The resting clasmatocytes cannot readily be differentiated from any other fusiform cell in sections of fixed tissues; while the lymphocyte may appear, in such sections, as an apparently isolated small round mononuclear cell, with no visible relation to the perivascular apparatus.
THE RELATION OF MONOCYTES AND CLASMATOCYTES TO EARLY INFECTION IN RABBITS WITH BOVINE TUBERCLE BACILLI
Authors: Sabin Florence R. , Doan Charles A.
Published: June 2004

1. The early reaction to intravenous tubercular infection in the various organs of the rabbit reveals a pathognomonic response in the lungs within 24 hours; the specific response in the liver, spleen, lymph glands, and bone marrow, follows from the 6th to the 14th days.

2. The development and extent of the pathologic process has been analyzed in terms of the activity of monocytes and clasmatocytes.

3. The criteria for differentiating these mononuclear phagocytic cells into two strains have been analyzed and the technics discussed.

4. The clasmatocyte phagocytizes tubercle bacilli freely and fragments them, as it does all cellular and other debris.

5. The monocyte stimulated to metamorphose into the typical epithelioid and giant cell of the Langhans type retains the tubercle bacilli intact, with power to survive and multiply, over long periods of time.

6. The normal number of monocytes or the degree to which monoblasts may be stimulated to development and maturation, together with the activity of the clasmatocytes in destroying bacilli, in any particular region, would appear to be a function of the rapidity and extent of the local tubercular involvement.
THE BIOLOGICAL REACTIONS IN RABBITS TO THE PROTEIN AND PHOSPHATIDE FRACTIONS FROM THE CHEMICAL ANALYSIS OF HUMAN TUBERCLE BACILLI
Authors: Sabin Florence R. , Doan Charles A.
Published: June 2004

1. The clasmatocyte, the cell with the power of fragmenting tubercle bacilli, the cell making the lesion of the so called interstitial pneumonia, has been shown to be the overwhelming response to the special protein fractions, 304 and 903. Multiple hemorrhages, high fever, and toxicity have marked the use of these fractions in every instance.

2. The epithelioid and the giant cell of the Langhans type, making typical tubercular tissue, have been the massive and specific response of the peritoneal cavity to intraperitoneal injections of the phosphatide fractions, A-3 and A-4. These fractions have been entirely non-toxic in the dosages used.
THE EFFECT OF SERUM UPON THE GERMICIDAL ACTION OF SOAPS
Authors: Eggerth Arnold H.
Published: June 2004

1. Far more information about the effect of serum or other substances upon the germicidal action of soaps can be obtained by determining the germicidal titers over a wide range of pH than by determining the titer at a single pH. In this way a characteristic curve for each test substance is obtained.

2. The curve for a particular concentration of serum bears a definite relationship to the curve for salt solution (buffer) alone. Wherever the titer in salt solution is high, very small amounts of serum greatly diminish that titer. Wherever the titer in salt solution is low, small amounts of serum leave the titer unchanged. Thus small additions of serum flatten the curves and make them more nearly horizontal. If further large amounts of serum are added, a further reduction in titer takes place at all reactions.

3. The calcium of serum has only a very slight effect upon the soap titer.

4. The protein of serum is probably inhibitory to soaps; but the curve for partially defatted serum, and the curves for other protein substances tested, do not run parallel to the serum-soap curves.

5. The various lipoids that are known to be present in serum are inhibitory to the action of soaps, both as emulsions and as clear solutions.

6. The action of serum upon soaps may be regarded as a complex reaction, in which lipoids, protein, and, to a lesser extent, calcium salts take part. Their effect is due to the fact that these substances, by combining with the soaps, remove them from the field of germicidal action.
THE INFLUENCE OF PROTEIN-FREE LIVER AND SPLEEN EXTRACTS ON THE BLOOD REGENERATION AND RESPIRATORY EXCHANGE OF ANEMIC RABBITS
Authors: Jeney A.
Published: June 2004

1. Respiratory exchange measurements may be used for gaining further evidence concerning the body changes during anemia, and are complementary to the hematological and histological data.

2. The heat production during anemia was slightly decreased. At the 3rd week it began to rise.

3. A protein-free liver extract has accelerated blood regeneration and at the same time increased the respiratory exchange of anemic animals.

4. A protein-free spleen extract has distinctly lowered the respiratory exchange of normal animals. The metabolism of anemic animals thus treated was practically the same as before bleeding and treatment.

The recovery of the spleen extract-treated animals was not complete during the period of observation. This extract may have been somewhat toxic. In spite of this disturbing factor we are not inclined to accept the view of C. D. and E. W. Leake (15) and Thalhimer (16) that the spleen takes part in the stimulating effect upon blood regeneration when given in combination with red bone marrow by mouth.