bluuebunny/crossref_metadata_2025 huggingface dataset:
STUDIES ON THE ETIOLOGY OF RABBIT POX
Authors: Rosahn Paul D. , Hu Ch'uan-K'uei , Pearce Louise
Published: June 2004

The results of serum neutralizing tests with the viruses of pox, vaccinia, and virus III disease herewith reported generally agree and supplement the results of reinoculation experiments on immune rabbits reported in the previous paper (1).

The finding that pox virus is neutralized by pox immune serum indicates that the refractory state of recovered pox rabbits to reinoculation with pox virus and the failure of recovered pox rabbits to contract a second pox infection after adequate exposure is to be explained upon the basis of the development of an active immunity.

The failure of virus III immune serum to neutralize pox virus is in agreement with the previous conclusion drawn from the positive results of reinoculation and exposure experiments that there is no specific relationship between pox virus and virus III.

Rabbits which had recovered from a pox infection were completely refractory to inoculation with dermo-(culture) vaccine, while rabbits which had recovered from vaccinia were partially refractory to inoculation with pox virus. Vaccine immune adult rabbits did not show any clinical evidence of pox upon exposure to florid cases, but young recently weaned vaccine immunes developed definite although comparatively mild pox infections. The serum neutralization tests showed that pox immune serum neutralized vaccine virus although the action was not complete as shown by the positive results obtained with high dilutions of serum; vaccine immune serum possessed some but comparatively slight neutralizing properties against pox virus. The results of the crossed inoculation and serum neutralizing experiments with pox and neurovaccine viruses resembled those obtained with pox and dermo-(culture) vaccine but the differences were less pronounced. The differences in virus neutralizing ability on the part of the three immune sera paralleled the differences in virus potency as indicated by the character of the local lesions at the site of injection and by the general character of the clinical manifestations of the infection. The potency or virulence of pox virus was much greater than that of neurovaccine and vastly greater than that of dermo-(culture) vaccine.

The complete identity of pox and vaccine virus could not be established, but a definite relationship between them was demonstrated and this was shown to have an immunological basis. From a practical standpoint vaccination with vaccine virus as a prophylactic measure against rabbit pox was clearly indicated.
MENINGITIS IN MAN CAUSED BY A FILTERABLE VIRUS
Authors: Rivers Thomas M. , Scott T. F. McNair
Published: June 2004

Evidence was presented substantiating the idea that our active agent is a virus. The reactions produced in laboratory animals by the active agent were described, and a comparison of it with other viruses was made. The results of experiments indicating the immunological identity of our virus, Armstrong and Lillie's virus of lymphocytic choriomeningitis, and Traub's virus were given in detail. Finally, the evidence in regard to its natural host and its importance as a factor in diseases of human beings was presented and discussed.
STUDIES ON AN UNCOMPLICATED CORYZA OF THE DOMESTIC FOWL
Authors: Nelson John B.
Published: June 2004

Minute coccobacilliform bodies have regularly been found in the nasal exudate of fowl infected both by injection and by contact with the coryza of slow onset. These bodies are commonly less than 0.5µ in diameter and are predominantly extracellular. They have consistently failed to grow in artificial media. They are held back by Berkefeld V filters which are impermeable to Hemophilus gallinarum but may pass through filters which are permeable to the test organism. The coccoid bodies are morphologically similar to a cultivable non-infective bacterium which may occasionally be isolated from exudate of the infected fowls.
CONCERNING THE RELATION OF ENVIRONMENTAL TEMPERATURE TO RESISTANCE TO THYROID AND THYROXINE, AND THE CREATINE CONTENT OF THE HEART AND OTHER TISSUES IN EXPERIMENTAL HYPERTHYROIDISM
Authors: Bodansky M. , Pilcher J. F. , Duff Virginia B.
Published: June 2004

Experiments have shown that the survival period of thyrotoxic rats is markedly influenced by the environmental temperature, being of much longer duration at low than at high temperatures. Between 22° and 37.5°C., the relation of temperature to the survival period is approximately linear. The tolerance to relatively large doses of thyroid and thyroxine is considerably increased below 20°C., but is especially striking at 4–6° C.

Hyperplasia of the thyroid, which results from exposure to cold, may be prevented by the administration of desiccated thyroid or thyroxine.

The diminished concentration of creatine of the myocardium, which is a conspicuous finding in rats treated with thyroid substance, does not occur in physiological hyperthyroidism resulting from long continued exposure to a low thermal environment.

In rats kept at high temperatures, whether treated with thyroid substance, or not, there is apparently no storage of colloid in the gland. The significance of the relatively high values for heart creatine in these animals at time of death is briefly discussed.
AN EPIDEMIC IN A MOUSE COLONY DUE TO THE VIRUS OF ACUTE LYMPHOCYTIC CHORIOMENINGITIS
Authors: Traub Erich
Published: June 2004

A filtrable virus, identical with that which causes acute lymphocytic choriomeningitis, has been found to cause a disease in white mice.

Naturally infected mice usually show no symptoms, but such animals inoculated intracerebrally with sterile bouillon or other materials develop characteristic symptoms. The same symptoms are produced by intracerebral injection of the virus into mice from a disease-free stock. Guinea pigs are very susceptible and are therefore useful for detecting the virus and for neutralization tests. The disease in both naturally infected and inoculated animals is discussed and the pathological findings given.
RELATION OF THE HYPOPHYSIS TO THE SPLEEN
Authors: Perla David
Published: June 2004

1. Removal of the hypophysis in adult rats is followed by progressive atrophy of the spleen. At the end of 2 months the ratio of spleen weight to body weight is one-half the normal. The administration of hypophyseal emulsion repairs to a considerable degree the atrophy of the spleen in such animals.

2. Hypophysectomy completely inhibits the regeneration of splenic tissue after partial splenectomy. Administration of anterior hypophyseal emulsion restores the regenerative capacity of splenic tissue of the hypophysectomized rat to the normal.

3. The daily administration of anterior hypophyseal emulsion of cattle or of alkaline extracts of fresh or acetone-dried anterior hypophysis during a period of 10 days in normal Bartonellacarrier or Bartonella-free rats results in hypertrophy of the spleen to twice normal size. Normal rats receiving emulsion during a period of 1 month become refractory to the spleen-stimulating effect. The spleen shows little increase in size above the normal at the end of this period. Injections of horse serum or of alkaline extracts of acetone-dried kidney, spleen or liver of cattle did not cause enlargement of the spleen of rats of Barlonella-free stock.

4. The increase in the size of the spleen, following daily administration of emulsion of the anterior hypophysis, is due primarily to a marked hyperplasia of the reticular and endothelial cells of the red pulp. The follicles also increase in size. Clusters of reticular cells containing numerous lymphoid elements appear throughout the splenic pulp. The reticular tissue of the bone marrow is similarly increased. There is a striking increase in the number of hemocytoblasts and megakaryocytes. The Kupffer cells are not affected.

5. The spleen-stimulating factor is not present in the acid extract of anterior hypophysis that contains thyrotropic and adrenotropic factors. It is present in some degree in an alkaline extract of fresh anterior hypophysis containing growth and gonadotropic factors. It is also present in alkaline extracts of acetone-dried anterior hypophysis relatively free from growth hormone.

6. The presence of a spleen-stimulating factor in the anterior hypophysis is suggested by these experiments.
CHEMICAL STUDIES ON BACTERIAL AGGLUTINATION
Authors: Heidelberger Michael , Kabat Elvin A.
Published: June 2004

1. The absolute, quantitative agglutinin method has been used for the determination of the presence or absence of small amounts of specific polysaccharide in pneumococcus variants.

2. A technique is described for the removal of group specific antibody from antipneumococcus horse serum.

3. The type specific anticarbohydrate agglutinin and precipitin are not only present in identical amounts in Type I antipneumococcus horse serum, but a reduction in one is also accompanied by a quantitatively identical reduction in the other, providing evidence for their actual identity. In purified antibody solutions somewhat more agglutinin than precipitin is found, possibly owing to alteration of a portion of the antibody in the process of purification.
ACTIVE IMMUNIZATION OF GUINEA PIGS WITH THE VIRUS OF EQUINE ENCEPHALOMYELITIS
Authors: Cox Herald R. , Olitsky Peter K.
Published: June 2004

From a study by quantitative methods, the conclusion is reached that a resistance of high degree may be induced in guinea pigs and mice against experimental equine encephalomyelitis by means of formolized vaccines in which no active virus can be demonstrated. The induced resistance is not due to residual traces of active virus which might possibly have escaped detection in the formolized tissue preparations.
STUDIES WITH HUMAN INFLUENZA VIRUS CULTIVATED IN ARTIFICIAL MEDIUM
Authors: Magill T. P. , Francis Thomas
Published: June 2004

The in vitro cultivation of strains of human influenza virus has been successfully conducted through a prolonged series of successive transfers. The cultivated virus has retained the antigenic and immunological properties which characterized the animal passage virus from which it was derived. The culture virus is still virulent for mice and ferrets; it is capable of inducing an active state of immunity in animals vaccinated subcutaneously or intraperitoneally; it elicits specific neutralizing antibodies in the serum of infected or vaccinated animals.

The virus has been successfully cultivated to date only in the presence of oxygen; when conditions of reduced oxygenation are imposed by the use of vaseline seal, with or without the addition of cystein, multiplication of the virus is not supported. On the other hand, it has been possible to cultivate the virus in the medium of Li and Rivers in ordinary test tubes. This affords a greatly simplified procedure, since the interval between transfers may be prolonged.

The results of neutralization tests with various sera and the culture virus are presented and discussed.
ON GROUP SPECIFIC A SUBSTANCES
Authors: Landsteiner K. , Chase M. W.
Published: June 2004

A method of preparation and a preliminary chemical investigation of the substance present in commercial (pig) pepsin which reacts with human A antiserum are presented. The material offers especial advantage in securing in quantity a serologically highly active preparation suitable for further studies. Active preparations were isolated moreover from commercial (pig) gastric mucin. Some other materials showing group specific reactions are mentioned.
QUANTITATIVE STUDIES ON THE PRECIPITIN REACTION
Authors: Heidelberger Michael , Kendall Forrest E. , Teorell Torsten
Published: June 2004

1. A quantitative study has been made of the effect on the precipitin reaction between the specific polysaccharide of Type III pneumococcus and the homologous antibody of salt concentrations ranging from O.1 M to 1.79 M, including the effect of ions of higher valence.

2. Within these limits, observed decreases in precipitated antibody with increasing salt concentration appear to be due to a decrease in the amount of antibody combined with the S III, rather than to an increase in solubility of the S III-antibody compounds.

3. The egg albumin-antibody reaction is far less sensitive to changes in salt concentration than is the S III-antibody reaction.
PERSISTENCE OF LYMPHOCYTIC CHORIOMENINGITIS VIRUS IN IMMUNE ANIMALS AND ITS RELATION TO IMMUNITY
Authors: Traub Erich
Published: June 2004

In some apparently healthy mice the virus of lymphocytic choriomeningitis persisted for a considerable period of time after recovery, in the blood, urine, and nasal secretions, while in other mice it soon became undemonstrable. It is possible that the persistence of the virus is due to lesions in the lungs, liver, and kidneys.

The immunity to lymphocytic choriomeningitis in mice does not seem to depend upon the presence of virus in the blood and the organs tested. No antivirus was detected in sera from several solidly immune mice, which fact suggests that circulating antivirus plays no important part in their immunity. Leucocytes also seem to be no essential factor in this immunity, which probably is closely linked with the tissues.

The urine of guinea pigs which had recovered from severe attacks of lymphocytic choriomeningitis contained virus for a few weeks after recovery, while that from mild cases contained no virus. Virus was never demonstrated in the blood of immune guinea pigs. Antivirus was readily detected in it.
THE INFLUENCE OF INTRAUTERINE FACTORS ON THE FETAL WEIGHT OF RABBITS
Authors: Rosahn Paul D. , Greene Harry S. N.
Published: June 2004

Observations were made on 475 fetuses carried by 71 pregnant rabbits. 63 or 88.7 per cent of the 71 does were sacrificed from 28 to 31 days after the last fertile mating, and these does bore 401 or 88.2 per cent of the total of 455 fully developed fetuses. The following information was available with reference to each fetus: age, weight, weight of corresponding placenta, horn, i.e., right or left, presentation, and position or order. The presentation indicated that part, head or breech, which was directed toward the vagina, and position or order, the relative locus of the fetus in the horn, the first position being that nearest the ovary.

As the gestation period approached its normal limit of 31 days, the relative daily increase in mean fetal weight was progressively retarded.

There was no significant difference between the number of fetuses in each uterine horn.

Head presentation was significantly more frequent than breech, but the uterine horn in which the fetus was located had no influence on its presentation.

A greater relative number of breech presenting fetuses was observed in the third position than in the other positions.

Presentation did not exert a significant influence on fetal weight.

Fetal weight at or near term was significantly influenced by the position or order in the uterine horn. In general, the weights of fetuses implanted high up nearest the ovary were greater than those developing nearest the outlet, and fetuses occupying intermediate positions had intermediate weights. When, however, only two fetuses were present in a horn, position had no effect on their weights.

A significant positive coefficient of correlation was observed between fetal and placental weights. Moreover, placental weight was influenced by position in the uterine horn in exactly the same manner that fetal weight was so influenced.

The factors which produced variability in fetal weight at or near term, did not account for the abnormally low birth weights of the dwarf rabbits observed in this laboratory.
THE IMMUNOLOGICAL SPECIFICITY OF STAPHYLOCOCCI
Authors: Julianelle L. A. , Hartmann A. F.
Published: June 2004

1. Skin reactions to the type specific carbohydrates of Staphylococcus indicate that cutaneous sensitivity to Type B is either extremely rare or nonexistent.

2. Skin reactions to Type A carbohydrate occur in about 12 per cent of normal infants and children and in 65 to 70 per cent of normal adults.

3. Skin reactions to Type A carbohydrate occur regularly in patients with Staphylococcus infection.

4. Skin reactivity is not associated with demonstrable serum precipitins, for (a) normal individuals, though skin reactive, have not been found to possess them, and (b) not all patients with verified infection develop them.

5. The patients elaborating type specific precipitins, who numbered less than 30 per cent in this study, are those with severe, prolonged, or generalized Staphylococcus infection.

6. Specific carbohydrates have not been found in the urine of patients during Staphylococcus infection.
EFFECT OF PURIFIED ENZYMES ON VIRUSES AND GRAM-NEGATIVE BACTERIA
Authors: Merrill Malcolm H.
Published: June 2004

Evidence is presented that some viruses behave like proteins in that they are inactivated by proteolytic enzymes, whereas others prove more or less resistant. Ten strains of living Gram-negative bacteria resisted the action of purified trypsin and chymotrypsin, while the killed organisms were rapidly digested. Gram-positive bacteria, on the other hand, were resistant whether living or dead. The findings are discussed.
CHEMO-IMMUNOLOGICAL STUDIES ON CONJUGATED CARBOHYDRATE-PROTEINS
Authors: Goebel Walther F.
Published: June 2004

1. Artificial carbohydrate-protein antigens containing the azobenzylglycosides of glucose and glucuronic acid give rise in rabbits to antibodies which are distinct and immunologically specific.

2. The artificial antigen containing glucuronic acid reacts in high dilutions in antipneumococcus horse sera Types II, III, and VIII. The chemical basis for this serological activity is discussed.
SEROLOGICAL REACTIONS WITH A VIRUS CAUSING RABBIT PAPILLOMAS WHICH BECOME CANCEROUS
Authors: Kidd John G. , Beard J. W. , Rous Peyton
Published: June 2004

A method has been devised for serological tests with a virus producing rabbit papillomas that become carcinomatous. The discrete character of the growths caused by the virus when suitably diluted fits it notably for quantitative experimentation. It shows no tendency to lie latent in domestic rabbits though it does so on occasion in cottontails, the natural hosts. Sera which partially neutralize it do not alter its character, or attenuate it, but merely cut down the number of its effective entities.

The serum of normal domestic rabbits is ordinarily devoid of neutralizing influence on the virus, but that of animals carrying the papillomas usually exhibits neutralizing power soon after these appear. The rate at which this power increases depends in general upon the amount of papillomatous tissue developing, but exceptions to the rule occur, the presence of fairly large growths being compatible with a lack of such powers in demonstrable amount. Even when the antiviral power is great it has no evident influence on the course of established papillomas, other factors determining whether these enlarge or retrogress. It acts to prevent successful reinoculation of the animal, however.
CHANGES IN THE BONE MARROW AND BLOOD CELLS OF DEVELOPING RABBITS
Authors: Sabin F. R. , Miller F. R. , Smithburn K. C. , Thomas R. M. , Hummel L. E.
Published: June 2004

1. The full number of erythroid cells in the blood stream of the rabbit is reached by the 3rd week of life.

2. During this period, there is a predominance of erythrogenesis in the bone marrow.

3. During the 2nd week of life the bone marrow is in a state of hyperplasia owing to the needs of the body for blood and the small space available for the marrow.

4. This hyperplasia is reduced as the growth of the bone permits the marrow to spread. The control of the growth of the bones has an important bearing on hematopoiesis.

5. During the first 3 weeks of life, the chemical factors for the multiplication of red cells as well as for the elaboration of hemoglobin become available.

6. The amount of hemoglobin does not increase as rapidly as the number of cells, so that the macrocytic anemia of the fetus becomes reduced. The proportion of hemoglobin per red cell characteristic of the adult rabbit is reached by the 3rd month.

7. Further evidence on the intravascular origin of red blood cells is given.

8. The development of all of the white blood cells, with the exception of the monocyte, goes on at a slower rate than that of the red cells.

9. The monocytes reach their full number in the blood stream in the 1st week of life; granulocytes and lymphocytes by the 5th and 6th months.

10. Each of the three strains of white cells has a different rate of development.

11. The question as to whether the stem cell or primitive cell is identical with the lymphocyte is discussed.
SURVIVAL OF THE VIRUS OF POLIOMYELITIS IN THE ORAL AND NASAL SECRETION OF CONVALESCENTS
Authors: Kramer S. D. , Sobel A. E. , Grossman L. H. , Hoskwith B.
Published: June 2004

The positive detection of the virus of poliomyelitis in the nasal secretions of 2 children, 16 and 13 days after the onset of the disease, is described. 7 animals which had been inoculated with other concentrates became ill with symptoms and temperature elevations suggestive of poliomyelitis, from 1 to 3 weeks following inoculation, but without definite paralysis. In 2 of these animals which were sacrificed, the histologic findings were compatible with the diagnosis of poliomyelitis but were not typical. Of the serums of the 5 remaining animals 4 failed to neutralize stock virus, whereas the serum of the fifth neutralized the virus on two different occasions. This serum was obtained from a monkey that had been inoculated with concentrated nasal secretions of a child 43 days after the onset of illness.

It is suggested that the present quarantine period of 3 weeks is compatible with the available data. It is further suggested that the methods of procedure described may be useful in similar investigations.
THE COMPLEMENT FIXATION REACTION WITH PNEUMOCOCCUS CAPSULAR POLYSACCHARIDE
Authors: Goodner Kenneth , Horsfall Frank L.
Published: June 2004

1. Complement is not fixed by immune aggregates resulting from the interaction of pneumococcus capsular polysaccharide and type-specific immune horse serum, although under proper conditions the substitution of immune rabbit serum gives positive results.

2. The negative results with immune horse serum are due to some poorly understood property of the specific antibodies rather than to some heterologous inhibitor present in the serum.

3. It has been shown that with immune rabbit serum-polysaccharide combinations, complement fixation is an adsorptive phenomenon conditioned upon the surface exposure of the immune aggregates.

4. A close parallelism to the selective adsorption of phosphatides by these immune aggregates has been pointed out.

5. In those instances in which complement is fixed this phenomenon must be regarded as tertiary and conditioned by (a) union of antigen and antibody, and (b) particulation.

6. The general significance of complement fixation as applied to bacterial polysaccharides has been discussed.
STUDIES ON NATURAL IMMUNITY TO PNEUMOCOCCUS TYPE III
Authors: Enders John F. , Shaffer Morris F. , Wu Chao-Jen
Published: June 2004

Among the experimental findings reported in this paper to which we wish to give particular emphasis are the following:

1. The results which follow the intravenous injection into rabbits of two strains of Pneumococcus Type III of different degrees of virulence vary with the state of the capsule. Thus when this structure is completely developed both remain in the blood. A culture of either strain begins to become susceptible to the blood-clearing mechanism contemporaneously with the onset of capsular degeneration and the initiation of other concomitant changes at the surface of the organism (cf Paper II), which occur much earlier with the less virulent strain.

2. When, in either case, removal from the blood stream occurs, this is effected by the phagocytic cells of the body. There is no suggestion that a new or unknown mechanism is involved. The greatest share of the burden is borne by the fixed phagocytic cells of the liver and spleen, and to a less extent by those of the lung and bone marrow. Nevertheless, it has been demonstrated that the polymorphonuclear leucocytes may also participate.

3. Phagocytosis by the leucocytes of the normal animal either in intro or in vivo has been observed only at such a time as the capsule has become impaired. Ingestion of the organisms by the fixed tissue cells appears also to be effective only under the same condition and is accordingly observed with much younger cultures of the less virulent strain.

4. Following their removal from the blood and their accumulation within the fixed phagocytes of the organs, destruction of most of the cocci proceeds within 2 to 4 hours. Both strains are destroyed provided they are in the state favorable to phagocytic attack.

5. Evidence has been presented which indicates that just as in vitro, so in a local area of inflammation within the body, aging with attendant capsular loss and increasing susceptibility to phagocytosis may take place.

6. With organisms from either strain a variable period of lag follows their injection into the blood stream, even when they are introduced in a state of active multiplication and complete encapsulation.

7. Differences in virulence for rabbits of two strains of Pneumococcus Type III do not imply that this animal possesses a defensive mechanism which is absent in other species, since it has been possible to demonstrate similar differences when the organisms are injected intravenously into mice. This fact indicates that the factors determining the degree of virulence of these strains are to be sought in the organisms themselves, rather than in the kind of host.
TISSUE CULTURE STUDIES ON BACTERIAL HYPERSENSITIVITY
Authors: Moen Johannes K.
Published: June 2004

1. Guinea pigs infected with naturally pathogenic hemolytic streptococci (group C—Lancefield) develop a low grade chronic type of disease characterized chiefly by purulent lymphadenitis.

2. Cutaneous hyperreactivity to a crude streptococcal extract invariably occurred during the course of this infection.

3. Production of antibodies (precipitins and agglutinins) was studied.

4. The hemolytic streptococcal extract had a specific toxic effect, when tested in vitro, on cells from infected animals; this was shown by microscopic evidence of cellular injury, and by quantitative inhibition of cellular migration and growth. The specificity of the reaction was proven by testing with other cytotoxic substances.

5. There was no parallelism between skin hypersensitivity and humoral antibody titer.

6. There was no correlation between the degree of skin reactivity to the bacterial extract and the degree of sensitivity of splenic cells to the toxic action of the same extract in vitro.

7. Comparison of cellular sensitivity to tuberculin with cellular sensitivity to streptococcal extract in cultures of guinea pig tissues showed that the former was more intense and was more persistent on prolonged growth in vitro.
OBSERVATIONS ON THE RELATION OF THE VIRUS CAUSING RABBIT PAPILLOMAS TO THE CANCERS DERIVING THEREFROM
Authors: Rous Peyton , Kidd John G. , Beard J. W.
Published: June 2004

All the strains of the Shope virus thus far tested which give rise to vigorous, progressively enlarging papillomas in domestic rabbits, function as carcinogenic agents by way of these growths. The more pathogenic the virus as evidenced by the brevity of its incubation period and the vigor of the papillomas produced, the sooner and oftener does cancer occur. The number of virus entities contained in the inoculum notably influences the outcome, cancer appearing most frequently in those confluent, papillomatous masses which have resulted from the greatest concentration of the virus material under test. The papillomas experimentally induced by the ordinary inoculation methods are essentially aggregates of proliferating cell families, each the outcome of some primary cell-virus association. Some of these associations are followed more frequently by cancer than others are in the same animal.

Cottontail rabbits, the natural hosts of the virus, are notably resistant to its sustained activity, as compared with domestic rabbits. Though often growing rapidly at first, the papillomas of cottontails soon become relatively inert in most cases, and they usually retrogress, and rarely undergo malignant change. In an instance here reported both a squamous cell carcinoma and a metastasizing sarcoma appeared at the base of some papillomas due to experimental inoculation, which had existed on the ears of a cottontail for nearly 2 years.

The meaning of the phenomena is discussed.
STUDIES ON NATURAL IMMUNITY TO PNEUMOCOCCUS TYPE III
Authors: Enders John F. , Wu Chao-Jen , Shaffer Morris F.
Published: June 2004

Since there is no evidence for the occurrence of type specific antibody in the normal rabbit and since, as we have shown, the Pneumococcus Type III whether avirulent or virulent is not removed from the blood stream or destroyed when the capsule is intact, the following factors which have been revealed in the course of our work appear to represent certain essential components, if not the complete mechanism, upon which the natural immunity of the rabbit against this organism depends. (a) The elevation of the body temperature after intravenous infection to 41°C. or thereabouts and its maintenance for varying periods. (b) The ability of the phagocytic cells, both fixed and mobile, to attack any cocci which have become vulnerable through the deterioration of capsular integrity. (c) The adjuvant effect of an antibody, reacting with the somatic C carbohydrate, which enhances the phagocytosis of such organisms as no longer possess a completely intact envelope.

Conversely, the varying degrees of virulence for rabbits observed among Pneumococcus Type III strains are based upon: (a) differences in the ability of the organisms to multiply at the elevated temperatures encountered in the infected host. Strains markedly susceptible to the harmful influence of this factor fail to induce a generalized fatal infection. Not all "thermo-resistant" strains are highly virulent, however, and these may contrast sharply with regard to (b) size of the capsule and the ease with which it is impaired or completely lost. The capsules must be maintained intact for a sufficient time until multiplication of the organisms can proceed to such a degree that death of the host results. Avirulent strains even when capable of growth at 41°C. appear to be unable to satisfy this requirement.

The differences in virulence of various strains apparently conditioned by these factors are not limited solely to the case of the rabbit, since for at least two strains similar differences in virulence have been shown to exist when the intravenous route of infection is employed in mice.
IMMUNOLOGICAL AND CHEMICAL INVESTIGATIONS OF VACCINE VIRUS
Authors: Parker Robert F. , Rivers Thomas M.
Published: June 2004

Methods have been described by which the number of elementary bodies present in a suspension can be estimated. It has been shown that by means of replicate counts, in which the Petroff-Hausser chamber was used, a high degree of accuracy can be attained. By means of the Gates densitometer, the number of elementary bodies in a suspension can be determined with a coefficient of variation of about 3.0 per cent. A method has been described by which the accuracy of estimation of the infectious titer of a suspension can be increased without greatly enlarging the number of animals employed. This consists of selecting as the end-point that dilution of virus which on intradermal inoculation in a rabbit would lead theoretically to an equal number of positive and negative results. The statistical advantages of this method have been confirmed by the experiences of other laboratories.

By the application of the methods described, there was shown to be a direct correlation between the number of elementary bodies and the number of infectious units of virus present in a given suspension. At the mean of the distribution this ratio is as the logarithms 9.62 to 8.0. To extrapolate this curve, in order to determine the number of elementary bodies present in a single infectious unit, while tempting, is probably not justifiable. It must likewise be remembered that the data given apply to a particular strain of vaccine virus, and that the number of infectious units has been determined by intradermal inoculation of rabbits. It appears also that this method may be of value in studies of the virulence of different strains of vaccine virus, since by its application one may determine not only the infectious liter of a suspension, but its content of elementary bodies.

In the agglutination reaction it was found that optimum titers of serum were obtained when the test antigen contained from 2.0 x 109 to 1.05 x 1010 elementary bodies per cc. Approximately 1.95 x 108 particles per cc. of suspension were required for the production of visible agglutination.
A HIGH SPEED VACUUM CENTRIFUGE SUITABLE FOR THE STUDY OF FILTERABLE VIRUSES
Authors: Bauer Johannes H. , Pickels Edward G.
Published: June 2004

1. A high speed centrifuge is described in which the speed is limited only by the strength of the material of which the rotor is made. It carries sixteen tubes, each of which conveniently accommodates 7 cc. of fluid.

2. The centrifuge operates in a very high vacuum and therefore requires only a small amount of driving energy. The arrangement has been found to eliminate the possibility of producing injurious frictional heat.

3. The rotating parts are supported by anair-bearing and are driven by compressed air.

4. The centrifuge has been successfully operated at a speed of 30,000 revolutions per minute, representing a maximum centrifugal force in the fluid of 95,000 times gravity.

5 Celluloid tubes used for centrifugation of fluid at high speeds are described.

6. Experiments are described in which good sedimentation of the yellow fever virus was obtained.
HYPERSENSITIVENESS AND ANTIBODY FORMATION IN TUBERCULOUS RABBITS
Authors: Freund Jules , Laidlaw Elizabeth H. , Mansfield James S.
Published: June 2004

1. Rabbits infected with bovine tubercle bacilli develop hyper-sensitiveness to an intracutaneous injection of tuberculin. This sensitiveness appears from the 2nd to the 6th week after infection and increases rapidly thereafter. Tests, as a rule, show fluctuation in the intensity of the sensitization. Sensitization is followed by an interval of several weeks preceding death during which the animals fail to react.

2. Rabbits infected with bovine tubercle bacilli form antibodies that fix complement in the presence of tubercle bacilli. The antibodies appear after 2 weeks, increase during 6 to 10 weeks, and persist until the animals die.

3. In the later period of infection the skin fails to react to tuberculin at a time when the serum contains complement fixing antibodies.
LIPIDS AND IMMUNOLOGICAL REACTIONS
Authors: Horsfall Frank L. , Goodner Kenneth
Published: June 2004

1. Specific precipitates resulting from the interaction of the homologous capsular polysaccharide and Type I antipneumococcus horse and rabbit sera have been analyzed by gasometric micro methods for total nitrogen, lipid nitrogen, and lipid carbon.

2. Lipid may, under certain conditions, form as much as 51 per cent or as little as 4 per cent by weight of specific precipitates.

3. The total lipid content of specific precipitates, within the range studied, is entirely independent of the protein content.

4. Lipid nitrogen forms a very small but detectable portion of the total nitrogen of precipitates.

5. The absolute lipid content of precipitates is a function of the concentration of lipid in the reacting mixture prior to precipitation, and seems to be governed by the laws of adsorption phenomena.
THE RELATION BETWEEN ANTIANAPHYLAXIS AND ANTIBODY BALANCE
Authors: Morris Marion C.
Published: June 2004

1. Sensitized guinea pigs injected with normal rabbit or guinea pig serum previous to intravenous inoculation of antigen may be protected against a few lethal doses of antigen. The protection is greater with foreign than with homologous serum and appears to be related roughly to the amount of serum introduced.

2. Sensitized guinea pigs injected with antibody-containing serum preliminary to intravenous injection of antigen, show no greater refractoriness to anaphylaxis than do those injected with normal serum.

3. Moreover, in many instances, the injection of an excess of antibody into the circulation of sensitized guinea pigs, leads to an increased susceptibility of these animals to anaphylaxis.

4. These results indicate that an excess of circulating antibody is not responsible for a state of antianaphylaxis, but on the contrary, may contribute toward the anaphylactic reaction itself.
FURTHER STUDIES ON TYPHUS FEVER
Authors: Zinsser Hans , Macchiavello Attilio
Published: June 2004

1. Guinea pigs can be actively immunized against European typhus fever with homologous formalinized Rickettsia tissue cultures, provided sufficient amounts are injected. The method is suggested for practical application in man.

2. Serovaccination against European typhus fever can be successfully applied to guinea pigs by a variety of methods, the simplest of which consists of the injection of mixtures of virulent defibrinated guinea pig blood and convalescent guinea pig serum taken from 3 to 5 days after defervescence. Similar results can be obtained with mixtures in which tissue culture virus, either with convalescent guinea pig serum or with antimurine horse serum, is used. There is no indication so far that such animals become carriers.

Possible application of these methods to typhus epidemics is discussed.
STUDIES ON THE MECHANISM OF IMMUNITY IN TYPHUS FEVER
Authors: Castaneda M. Ruiz
Published: June 2004

This study of the lesions produced in the skin of guinea pigs inoculated intracutaneously with Mexican typhus virus, shows that there is an early polymorphonuclear response at the point of inoculation. As early as 24 hours after the virus is given, a mononuclear phagocytic infiltration, which is more pronounced around the larger vessels of the corium, vascularis, and muscularis, replaces the polymorphonuclear infiltration. The endothelial cells of capillaries and small vessels swell up, thus partially occluding the lumina. Rickettsia bodies are found in the swollen cells, in numbers which remind one of the intracellular Rickettsiae of the tunica in typhus infected guinea pigs. The mature Mooser's cells are found in abundance on the 3rd to the 4th day after inoculation. They are found in various positions as follows: (a) in the endothelial cells of capillaries, particularly in places of little or no infiltration; (b) within the mononuclear nodules formed around the larger vessels and within the dense infiltration of the vascularis (the parasitized cells are usually traced to a capillary wall); and (c) less frequently the organisms are found within the swollen cells of arterioles and small veins. The organisms disappear gradually from the zones of increasing polymorphonuclear infiltrations, suggesting that the presence of such polymorphonuclears is due to the bursting of the infected cells.

In the artificial lesions produced in the skin by the inoculation of considerable numbers of Rickettsiae, the tissue reactions are abnormally enhanced. One can see in the same slide different stages of the development of the lesions and their relationship to the infecting agent. The early perivascular infiltration by mononuclear phagocytes does not seem to be related to an actual infection of the endothelial lining by the inoculated virus, but seems rather, when properly controlled, to be primarily due to a nonspecific type of response. The capillaries or small vessels within these infiltrated zones may become parasitized and call forth a polymorphonuclear reaction which may thus transform the cytological picture of the nodule. The subsequent migration of macrophages terminates the histological sequence.

In capillaries apart from areas of cellular infiltrations, the polymorphonuclear reaction is first to appear, when the Rickettsiae are liberated from the cells.

One cannot safely generalize from the results observed in an artificial typhus lesion, but in the light of these observations, it is probable that the Rickettsia bodies are difficult to find in typhus patients or infected animals because they disappear rapidly from the nodules, or perhaps because some nodules are not necessarily related to an infected endothelium. At any rate, a late typhus lesion is not likely to reveal Rickettsiae which most probably have been removed by the early polymorphonuclear invasion.
STUDIES ON THE SENSITIZATION OF ANIMALS WITH SIMPLE CHEMICAL COMPOUNDS
Authors: Landsteiner K. , Jacobs John
Published: June 2004

Experiments are described which show that with a given treatment guinea pigs can be sensitized to arsphenamine, so that a considerable percentage die in anaphylactic shock on intravenous administration of the substance.
HUMORAL ANTIBODIES AND RESISTANCE OF VACCINATED AND CONVALESCENT MONKEYS TO POLIOMYELITIS VIRUS
Authors: Sabin Albert B. , Olitsky Peter K.
Published: June 2004

1. Monkeys convalescent from a paralytic attack of poliomyelitis develop humoral antibodies slowly; in the present series their first appearance in most was at 2 months and in some not until 3 months after the attack.

2. Convalescent monkeys display resistance to reinfection with the same strain by the nasal route long before antibodies become demonstrable in their serum, in this respect differing from many vaccinated monkeys whose serum neutralizes the virus, while they remain susceptible to nasal infection.

3. When antibodies appear in the serum of resistant convalescent monkeys, they are not quantitatively greater than in the serum of vaccinated monkeys which succumb to infection. As regards resistance to infection, humoral antibodies, therefore, do not have the same significance in vaccinated as in convalescent poliomyelitis monkeys.
STUDIES ON AN UNCOMPLICATED CORYZA OF THE DOMESTIC FOWL
Authors: Nelson John B.
Published: June 2004

The coccobacilliform bodies of fowl coryza were successfully cultivated in the fetal membranes of fertile eggs. Microscopic examination indicated growth in approximately 50 per cent of 94 eggs inoculated on the 3rd to 4th day of incubation. Growth was generally inhibited, however, in eggs inoculated on the 10th day. One strain of the specific bodies was maintained through 11 successive passages in 4 day eggs.

A more consistent growth of the coccobacilliform bodies was obtained in tissue cultures. One strain, originally isolated in November, 1935, has been carried through 100 successive subcultures at intervals of 1–3 days. The specific bodies fail to maintain their morphological identity for any length of time in this medium.

It is noted that growth of the coccobacilliform bodies in fertile eggs and in tissue cultures is not dependent on the presence of living cells.
STUDIES ON AN UNCOMPLICATED CORYZA OF THE DOMESTIC FOWL
Authors: Nelson John B.
Published: June 2004

Fetal membrane and tissue culture suspensions of the coccobacilliform bodies are infective for normal fowl. Intranasal injection is commonly followed by a coryza which is serially transmissible and communicable by direct contact. The specific bodies are generally demonstrable in the nasal exudate of birds infected either by injection or contact.

Compared with the original strain of the coryza of slow onset the reaction produced by these suspensions is often less vigorous; the incidence of apparent cases, characterized by a nasal discharge, being 97 per cent and 53 per cent, respectively. The apparent cases are similarly characterized by a long incubation period and a tendency towards chronicity.
IMMUNOLOGICAL STUDIES ON A NEW PREPARATION OF TYPE SPECIFIC POLYSACCHARIDE FROM PNEUMOCOCCUS TYPE I
Authors: Chow Bacon F.
Published: June 2004

A type specific polysaccharide has been isolated from the autolyzed broth of Type I Pneumococcus by a modified Avery and Goebel's method.

The newly prepared polysaccharide reacts with the homologous immune rabbit serum which has been completely absorbed with the acetyl polysaccharide of Avery and Goebel.

The newly prepared polysaccharide produces passive immunity in mice and rats and possibly in rabbits.

The antigenicity is not lost on boiling in acid or alkaline medium, but the precipitative activity is decreased.

In conclusion, it has been shown that the polysaccharide from Type I Pneumococcus, as isolated by a slight modification of Avery and Goebel's method, is a more complete antigen.
A QUANTITATIVE TECHNIQUE FOR PERFORMING PLASMAPHERESIS
Authors: Melnick Daniel , Cowgill George R. ,   With the Cooperation of Ethel Burack, Ph.D.
Published: June 2004

1. A special apparatus and technique are described which permit one to conduct plasmapheresis quantitatively.

2. The validity of the methods employed, for determining serum protein concentration and blood volume as prerequisites for the calculation of the amount of blood to be withdrawn, are discussed.
THE INFLUENCE OF DIET UPON THE REGENERATION OF SERUM PROTEIN
Authors: Melnick Daniel , Cowgill George R. , Burack Ethel
Published: June 2004

1. From a consideration of previous work related to the problem of the influence of diet upon the regeneration of serum protein, a plan of study is described which eliminates the many variables shown to be operating in the studies conducted by these pioneer workers.

2. By the administration of a protein-free diet at a high level of caloric intake to the dog subjected to plasmapheresis during which one-fourth of the blood volume of the animal is withdrawn daily, it is possible to reduce the serum protein concentration to the basal level (3.5 to 4.2 per cent) and to deplete the organism of its reserve stores of this protein within 1 week. The subsequent week has been demonstrated to be an equilibrium period.

3. The dog contains a reserve store of serum protein building material equivalent to about 30 to 40 per cent of the total amount normally present in the circulation.

4. When fed the protein-free diet and when subjected to quantitative plasmapheresis, whereby the basal level of the serum protein concentration is maintained constant, the dog is able in 1 week to regenerate approximately 20 to 30 per cent of the total amount of this blood protein normally present in the plasma.

5. The administration of a diet favorable for promoting the regeneration of serum protein requires approximately 4 to 5 days before a constant and maximal response to the dietary stimulus is obtained. Equilibrium data are yielded during the 2nd week, and these are employed in calculating the potency ratio of the dietary protein.
TISSUE CULTURE STUDIES ON BACTERIAL HYPERSENSITIVITY
Authors: Moen Johannes K.
Published: June 2004

1. Mononuclear exudative cells, obtained from tuberculous guinea pigs by the intrapleural injection of parowax, exhibited characteristic sensitivity to the toxic action of tuberculin when tested in tissue culture.

2. Experiments with these cells, practically free of body fluids, show conclusively that sensitivity to tuberculin is an inherent characteristic of mesenchymal cells from tuberculous animals.

3. Fibroblastic growths which developed from mononuclear exudative cells derived from a tuberculous animal showed persistence of sensitivity to the toxic action of tuberculin on repeated transplantations over a prolonged period in vitro.
EFFECT OF PNEUMOCOCCUS AUTOLYSATE ANTITOXIN ON PNEUMOCOCCUS PNEUMONIA IN GUINEA PIGS
Authors: Weld Julia T. , Gilder Helena
Published: June 2004

1. In rabbits, guinea pigs, and mice pneumococcus autolysate antitoxin has no effect against generalized infection by the pneumococcus.

2. In a large proportion of cases of pneumonia and sepsis caused by the intratracheal inoculation of large amounts of living pneumococci in normal or sensitized guinea pigs, autolysate antitoxin saves the animal.

3. The autolysate antitoxin is protective in most cases of pneumonia and sepsis caused by the intratracheal inoculation of small amounts of living pneumococci combined with sublethal doses of staphylococcus toxin.

4. These experiments indicate that in pneumococcus pneumonia of guinea pigs the autolysate toxin or toxins are elaborated only in the lungs.