bluuebunny/crossref_metadata_2025 huggingface dataset:
QUANTITATIVE STUDIES ON ANTIBODY PURIFICATION
Authors: Heidelberger Michael , Kabat Elvin A.
Published: June 2004

1. The salt dissociation and barium hydroxide-barium chloride methods are extended to the preparation of highly purified antibody solutions from specific precipitates derived from Type III and Type VIII antipneumococcus horse sera and a low grade polyvalent bovine serum. Analytically pure precipitin (agglutinin) was obtained from the last, and Types I, II, and III antibodies were separated.

2. Difficulties connected with the application of the methods to Type I antipneumococcus rabbit sera are described, as is also the purification of antibody from low grade pig and sheep sera.

3. The dissociation of antibody by both methods from Type I pneumococci agglutinated in antisera produced in the horse, rabbit, pig, and sheep, is described and its advantages discussed.

4. Certain theoretical aspects of the work are also discussed.
CANINE DISTEMPER IN THE RHESUS MONKEY (MACACA MULATTA)
Authors: Dalldorf Gilbert , Douglass Margaret , Robinson H. E.
Published: June 2004

Canine distemper has been transmitted to rhesus monkeys by a variety of methods. The disease is strikingly similar if not identical in its features with distemper in dogs.
TOXEMIA OF PREGNANCY IN THE RABBIT
Authors: Greene Harry S. N.
Published: June 2004

No definite conclusions relative to the etiology of toxemia of pregnancy in the rabbit can be drawn from the evidence obtained to date, but certain findings are suggestive and will be investigated further in future studies. These findings suggest that the disorder in the rabbit is a generic variation of eclampsia in man. The incidence, clinical manifestations and pathological lesions indicate that the disorder is of hypophyseal origin and that the association with pregnancy is due to altered activity of that gland in the terminal stages of gestation.

Hereditary factors related to race and certain constitutional variations were associated with increased susceptibility, but their expression was apparently dependent upon environmental conditions. The association of widespread reproductive disturbances with the outbreak of toxemia suggests a causal relation, and it is assumed that the endocrine imbalance was a primary factor in their genesis and was induced by changed environmental conditions. The general response of the population was manifest in functional disturbances which were of minor severity in normal groups and were expressed as toxemia in inherently susceptible animals.
THE EFFECT OF FORMALDEHYDE ON PNEUMOCOCCI
Authors: Dubos René J.
Published: June 2004

When used in low concentration, formaldehyde increases the rate of autolytic disintegration of pneumococci whereas in large concentrations it completely inhibits autolysis and preserves both the morphological and staining characteristics of the cells.

Pneumococci treated with large concentrations of formaldehyde, then washed free of the antiseptic and resuspended in physiological solutions, rapidly undergo a change which renders them Gram-negative and smaller. The lysis is only partial, however, and is not accompanied by an actual disintegration of the cell. It is caused by the autolytic enzyme of the cell which remains inactive in the presence of an excess of formaldehyde but recovers its activity when the cells are resuspended in a neutral medium after removal of the antiseptic. If the autolytic enzyme is irreversibly inactivated by heating, or maintained inactive in acid or alkaline reaction, the formolized cells retain their staining characteristics and morphological integrity.

Formolized pneumococci which have become Gram-negative owing to the action of their autolytic enzyme, fail to elicit the type specific carbohydrate antibodies in rabbits. Formolized pneumococci in which the autolytic enzyme has been destroyed or maintained inactive, and which have retained their Gram-positive character, function as a very effective type specific antigen in the rabbit.

These observations emphasize once more the close relation between the Gram-positive structure of pneumococci and the capsular polysaccharide antigen of the cell. They can be used as a basis for the preparation of suspensions of formolized pneumococci which are stable and very effective as type specific antigens.
EXPERIMENTAL SYPHILIS OF ORIENTAL ORIGIN: CLINICAL REACTION IN THE RABBIT
Authors: Pearce Louise
Published: June 2004

Two oriental strains of T. pallidum of Chinese origin were compared with two well known occidental strains, the Nichols and the Zinsser-Hopkins, on the basis of the clinical reaction to infection in the rabbit. Four experiments were carried out, two each in Peiping and New York. Animals from American and Chinese sources were represented in each experiment.

The results obtained showed that the reaction to both Chinese strains was generally comparable to that of the American strains. But with both Chinese strains, lesions of the eyes were more frequent, the time relations of certain phases of the reaction were shortened, and there was a higher incidence of complete recovery (latency) within the observation period. In view of the well known variability of the syphilitic reaction, however, it was not felt that these qualitative differences in clinical response could be ascribed to inherent or biologically fixed properties of the strains.
SOME EFFECTS OF FORMALDEHYDE ON HORSE ANTIPNEUMOCOCCUS SERUM AND DIPHTHERIA ANTITOXIN, AND THEIR SIGNIFICANCE FOR THE THEORY OF ANTIGEN-ANTIBODY AGGREGATION
Authors: Eagle Harry
Published: June 2004

Small amounts of formaldehyde inhibited the precipitating activity of horse diphtheria antitoxin with toxin and of horse antipneumococcus serum with the homologous capsular carbohydrate. Approximately 1 part of commercial formaldehyde to 1000 parts of serum, acting for 24 hours, inhibited the flocculating activity completely. In both cases, the combining affinity of the treated antibody for the corresponding antigen was not demonstrably affected, as determined both by in vitro experiments and by animal protection. More intensive treatment of the antipneumococcus serum caused an apparent loss of its bacterial agglutinating activity, but on centrifugation the organisms cohered: combination had occurred, and only the spontaneous aggregation was prevented. These effects are the same as those previously described for diazo compounds, and have been qualitatively reproduced with acetaldehyde, benzaldehyde and butyraldehyde.

The quantitative relationships suggest that only a few groups in the antibody molecule need be modified by formaldehyde in order to prevent aggregation; and it is probable that these are some of the free NH2 groups of the antibody protein. In marked contrast, the combining affinity of both antipneumococcus antibody and diphtheria antitoxin for the corresponding antigens was only slightly affected by amounts of formaldehyde which sufficed to block the free NH2 groups rapidly and almost completely. Similarly, this amount of treatment did not affect the reactivity of these two antisera acting as antigen with a rabbit antiserum versus horse serum. The integrity of the NH2 groups is apparently not essential for the activity of these sera acting either as antigen or as antibody; and the slow disappearance of their activity in concentrated HCOH is apparently to be ascribed to some secondary reaction other than the simple addition of HCOH to free NH2 groups.

The present experiments do not support the theory that antigen-antibody aggregates are lattice-like structures built up from elementary antigen-antibody compounds because of residual specific combining groups. The aggregating activity of both antipneumococcus serum and diphtheria antitoxin was completely inhibited by procedures which did not demonstrably affect their combining power with antigen. This suggests that the aggregation of antigen-antibody compounds is a secondary, non-specific reaction. It is perhaps significant that the amount of formaldehyde which just sufficed to prevent aggregation also caused a marked increase in the solubility of the pneumococcus antibody, which could then no longer be precipitated at serum pH by dilution with water or by dialysis. This strongly suggests that the loss of precipitating activity is actually due to the increased solubility of the antibody and supports the hypothesis that the primary cause of specific antigen-antibody aggregation is the relative insolubility of the bound antibody.
THE DEGREE OF COMPENSATORY RENAL HYPERTROPHY FOLLOWING UNILATERAL NEPHRECTOMY
Authors: MacKay Lois L. , Addis T. , MacKay Eaton M.
Published: June 2004

Compensatory hypertrophy of the kidney in albino rats is increased by an increase in the protein intake. The effect is greater in old rats than young rats. Successive increases in the protein intake are followed by a reduction in the increase in the degree of compensatory renal hypertrophy.
LOCAL RECOVERY IN EXPERIMENTAL PNEUMOCOCCUS LOBAR PNEUMONIA IN THE DOG
Authors: Robertson O. H. , Coggeshall L. T.
Published: June 2004

An investigation has been made of the process of local recovery occurring in the pulmonary lesions of dogs with experimental pneumococcus lobar pneumonia. Six animals showing simultaneous healing and spread of the pathological process in different parts of the lungs were sacrificed during the active stage of the disease for bacteriological and histological study. It was found that with few exceptions the clearing (resolving) lesions as revealed by x-ray during life were sterile on culture while the young, metastatic processes yielded an abundant growth of pneumococci. The resolving areas which represented the older lesions were characterized by the presence of a well developed macrophage reaction, whereas the early lesions consisted of alternating areas of edema and polymorphonuclear infiltration and contained usually many pneumococci both free and in the cells. The only pneumococci found in the areas of macrophage mobilization were intracellular forms, for the most part in the process of digestion. In several instances these striking differences in the cellular picture and the numbers and distribution of pneumococci were observed in different parts of a single lobe lesion. Tests on the blood serum failed to reveal any evidence of acquired antipneumococcal humoral immunity. The significance of these findings in relation to the mechanism of recovery is discussed.
THE INFLUENCE OF INFLAMMATION ON THE ABSORPTION OF SUBSTANCES OF VARIED DIFFUSIBILITY
Authors: Miller Rose G.
Published: June 2004

1. Inflammation retards the absorption of horse serum globulin and crystalline egg albumin from the peritoneal cavity and subcutaneous tissue, but retardation of the absorption of crystalline egg albumin is less than that of globulin, which is less diffusible.

2. Inflammation retards the absorption of the specific polysaccharide of pneumococcus Type I from the peritoneal cavity; inflammation may accelerate, but does not hinder, the absorption of glucose from the peritoneal cavity.

3. Inflammation retards the spread of trypan blue in the skin, but accelerates absorption from the skin of the more diffusible dye, brom phenol blue.

4. Phenol red is excreted in the urine with equal rapidity after injection into normal and into inflamed subcutaneous tissue or into normal and into inflamed peritoneal cavities. Direct extractions of phenol red from inflamed subcutaneous sites indicate that inflammation accelerates the absorption of the dye from these areas.

5. Inflammation retards the absorption of the indiffusible proteins, carbohydrates and dyes; it tends to accelerate the absorption of the diffusible carbohydrates and dyes.
THE EFFECT OF A TISSUE ENZYME UPON PNEUMOCOCCI
Authors: Dubos René J. , MacLeod C. M.
Published: June 2004

Polymorphonuclear leucocytes contain an enzyme which destroys the basophilic character of beat-killed pneumococci (R and S variants) and inactivates the type specific polysaccharide antigen of encapsulated cells. The same enzyme, however, fails to cause a disintegration of the bacterial cells, or to decompose the capsular polysaccharide itself.

The enzyme has been extracted from a number of animal tissues; it appears identical with a purified enzyme extracted from pancreatin and which decomposes yeast nucleic acid.

These facts are considered with regard to the failure of rabbits to produce the type specific carbohydrate antibodies when immunized with heat-killed encapsulated pneumococci by the intradermal route.
A STUDY OF THE BEHAVIOR OF FOWL POX VIRUS MODIFIED BY INTRACEREBRAL PASSAGE
Authors: Buddingh G. John
Published: June 2004

1. Intracerebral transfer in chicks of fowl pox virus produces marked changes in its behavior when studied in the chorio-allantoic membrane of chick embryos and in the skin of baby chicks.

2. A great and persistent increase in virulence for epithelial cells, characterized by rapid necrosis instead of proliferation and hyperplasia, is acquired by the virus propagated intracerebrally.

3. An affinity for cells of mesodermal origin including endothelial cells of blood vessels, and an increase in affinity for entodermal cells is acquired by the virus propagated intracerebrally.

4. The intracerebral virus causes a uniform morphological change in all types of cells, in that the infected cells rapidly become spherical in shape, detached, and desquamated followed by necrosis.

5. One intracerebral passage is sufficient to produce this change in the virus.
THE DEMONSTRATION OF LESIONS AND VIRUS IN THE LUNGS OF MICE RECEIVING LARGE INTRA-PERITONEAL INOCULATIONS OF EPIDEMIC INFLUENZA VIRUS
Authors: Rickard E. R. , Francis Thomas
Published: June 2004

Following the intraperitoneal inoculation of mice with large doses of epidemic influenza virus (50,000 to 1 million intranasal M.L.D.) it can be recovered from the lungs in high concentration, and pulmonary lesions of moderate extent may be observed. The virus reaches its highest titer in the lungs 48 to 72 hours after intraperitoneal injection and may persist for 10 days. Virus may be recovered from the blood in the first 24 hours, but is readily detected in the omentum and peritoneum for 5 to 6 days. Mice which as a result of the intraperitoneal injection of virus show a high concentration of virus in the lungs do not die but become solidly immune to intranasal infection. Moreover, as early as 24 to 48 hours after intraperitoneal inoculation of large amounts of virus the animals may exhibit resistance to infection with fatal doses of virus given intranasally.

Influenza virus given intravenously to mice is rapidly removed from the blood but persists in the lungs and induces pulmonary lesions. Virus can also be recovered from the liver for several days. With subcutaneous inoculation of influenza virus, however, the virus does not reach the blood or lungs in detectable amounts although the regional lymph nodes may yield considerable quantities of the agent.

A brief consideration is presented of the mechanisms of infection and resistance which may be involved.
HORMONE STUDIES WITH THE ULTRACENTRIFUGE
Authors: Chiles James A. , Severinghaus Aura E.
Published: June 2004

1. An ultracentrifuge is described in which the rotor is driven by a compressed air turbine, and is spun in an evacuated chamber to minimize friction and heating. The rotating parts are supported by a cushion of air in an air bearing.

2. The centrifuge rotor holds 10 test tubes inclined at 45° to the axis, and has a capacity of 55 cc. It is operated at a maximum speed of 51,000 R.P.M., which develops at the top of the fluid column in the test tubes a centrifugal field of over 100,000 times gravity, and at the bottom of the fluid column a field of over 200,000 times gravity.

3. By means of a reverse turbine, the rotor can be brought to a stop from full speed in a relatively short time.

4. A precession damping device is described, which effectively damps the precession and wobbling of the rotor that usually occurs at certain speeds in machines of this type.

5. A relatively long section of shaft is used between the centrifuge rotor and lower bearings. This prevents vibrations from being appreciably transmitted through the shaft to the lower bearings and driving mechanism, and results in a negligible wear on the bearings.

6. The driving mechanism is designed so that the positions of its parts are adjustable, and so that the driving mechanism may be dismantled without disturbing these adjustments.
CUTANEOUS INFECTIVITY IN EXPERIMENTAL POLIOMYELITIS
Authors: German William J. , Trask James D.
Published: June 2004

1. Bilateral olfactory neurectomy did not prevent experimental poliomyelitis on intravenous or intracutaneous inoculation.

2. Various operative procedures increased the susceptibility of monkeys to infection with experimental poliomyelitis.
EFFECT OF REPEATED SUPERINFECTION UPON THE POTENCY OF IMMUNE SERUM OF MONKEYS HARBORING CHRONIC INFECTIONS OF PLASMODIUM KNOWLESI
Authors: Coggeshall Lowell T. , Kumm Henry W.
Published: June 2004

Protection tests have been utilized to determine the effect of superinfection upon the potency of immune serum of monkeys with chronic Plasmodium knowlesi infections. The results of these tests showed that:

1. In 2 groups of monkeys with comparable P. knowlesi infections the immune serum of 8 monkeys which had been superinfected on 7 separate occasions over a period of 2 months was much more potent than the immune serum of a group of 7 monkeys which were allowed to continue their chronic course of infection without superinfection.

2. After a series of 9 more intense superinfections the serum from the same 2 groups of monkeys contained no demonstrable protective antibodies.

3. The serum from 8 of the 10 monkeys in the original 2 groups showed a relatively high concentration of protective antibodies following a month's rest and a single superinfection.

4. The results of the experiments indicate that it is possible to increase the potency of immune serum by superinfection, but it is also possible to obtain a decrease in the protective property of the serum by too severe superinfections.
QUANTITATIVE STUDIES OF BRUCELLA PRECIPITIN SYSTEMS
Authors: Pennell R. B. , Huddleson I. F.
Published: June 2004

Quantitative cross precipitation studies with goat antisera show the three endoantigens of the brucella to be serologically distinguishable. Although the endoantigens of Br. abortus and Br. suis are very similar, they do not react identically, permitting the serological distinction of the two organisms. These differences in cross precipitation may be used to identify an organism of the brucella group or to determine the organism responsible for a brucella antiserum.
PRODUCTION OF EXPERIMENTAL OSTEOMYELITIS IN RABBITS BY INTRAVENOUS INJECTION OF STAPHYLOCOCCUS AUREUS
Authors: Thompson R. H. S. , Dubos R. J.
Published: June 2004

1. The conditions under which a certain strain of staphylococcus (OH 172) causes in rabbits the development of bone inflammation have been described.

2. The virulence of the strain for rabbits was markedly raised by passage through this animal species, and especially after the culture had been recovered from a bone abscess.

3. The results indicate that it is possible to produce consistently inflammation of the bones of rabbits by the mere intravenous injection of a suitable strain of staphylococcus, without resorting to any elaborate operative technique designed to localize the organisms in the bones. It appears also that the inflammatory process so produced bears a close resemblance to staphylococcal osteomyelitis as occurring in human beings.
SENSORY NEURON DEGENERATION IN VITAMIN DEFICIENCY
Authors: Wintrobe Maxwell M. , Mitchell David M. , Kolb Lawrence C.
Published: June 2004

Young pigs were given an artificial diet presumably adequate in all respects. As they developed, the quantity of yeast was gradually reduced while thiamin (vitamin B1) and riboflavin were given in its place. The rate of growth decreased, the general condition of the animals became impaired, and marked ataxia without motor weakness developed. Histologically, severe degeneration of the posterior columns of the spinal cord, the dorsal root ganglion cells, and the peripheral nerves was found.
THE ISOLATION OF THE BLOOD GROUP A SPECIFIC SUBSTANCE FROM COMMERCIAL PEPTONE
Authors: Goebel Walther F.
Published: June 2004

The isolation of the blood group A specific substance from commercial peptone has been described. The chemical and serological properties of the material from that source have been defined.
FACTORS INFLUENCING THE PERSISTENCE OF CHORIOMENINGITIS VIRUS IN THE BLOOD OF MICE AFTER CLINICAL RECOVERY
Authors: Traub Erich
Published: June 2004

Mice infected in utero continued to carry choriomeningitis virus in the blood more regularly and in greater amount than suckling mice infected by contact. This result may be due to the difference in tissue maturity at the time of infection: the more immature the tissues are when infected, the longer the virus appears to persist in them after maturation. A similar result was obtained with mice of different ages infected either by contact or by intranasal instillation of virus, in that the carrier state lasted longer in the younger animals. This cannot be attributed entirely to the difference in age, however, since young mice as a rule showed more severe symptoms than mature animals. It is possible, therefore, that the difference in the severity of the disease accounted in part for that in the duration of the infection.

In mature mice infected experimentally as well as in some of the suckling mice infected by contact the severity of the disease was the determining factor, the infection persisting longest in those animals that showed the most severe reaction.

The character of the virus used also appeared to influence the persistence of the virus in the blood. A strain of virus isolated in 1935 from an infected stock mouse and modified by intracerebral passage in mice (5) disappeared from the circulation more rapidly than the stock strain maintained by natural passage in the infected mouse stock. The guinea pig passage strain, however, which was obtained from the same mouse as the mouse passage virus but passed through guinea pigs by pad inoculation, persisted in the blood more frequently than the stock strain.

Carrier mice without exception had a high degree of immunity to intracerebral injection with virus, while other animals once infected but no longer carrying detectable amounts of virus in the blood often showed an incomplete immunity that manifested itself in an accelerated, non-fatal reaction, presumably of an allergic nature. This observation does not prove, however, that the immunity always is an "infection immunity," since a high degree of resistance not associated with detectable amounts of virus in the blood and brain was produced by repeated injections with the mouse passage strain.

Since the blood and the tissues of old carriers often contain large amounts of virus, it is very unlikely that their immunity is due to protective antibodies circulating in the blood or fixed in the tissue spaces. It rather appears that the susceptible cells of such animals are infected and that cells occupied by actively multiplying virus cannot be reinfected. The mechanism of this infection immunity as well as the immunity apparently not associated with infection requires further study.
THE PASSAGE OF RABBIT VIRULENT TYPE III PNEUMOCOCCI FROM THE RESPIRATORY TRACT OF RABBITS INTO THE LYMPHATICS AND BLOOD
Authors: Schulz Reuben Z. , Warren Madeleine F. , Drinker Cecil K.
Published: June 2004

1. Rabbit virulent Type III pneumococci when instilled into the nose or trachea were recovered from the lymphatics draining the area involved in the lymph collected during a subsequent 4 hour period. Their detection rarely failed, and not infrequently was possible at the end of the 1st hour.

2. The organisms practically invariably appeared first in the lymphatics and subsequently in a few cases were recovered from the blood during the 4 hour test period.

3. The intravenous administration of antiserum 2½ to 3 hours before the instillation of organisms decreased the number of animals whose lymph or blood became positive and the total length of time in which organisms were recovered in lymph from the efferent lymphatics during the test period.
MOLECULAR WEIGHT, ELECTROCHEMICAL AND BIOLOGICAL PROPERTIES OF TUBERCULIN PROTEIN AND POLYSACCHARIDE MOLECULES
Authors: Seibert Florence B. , Pedersen Kai O. , Tiselius Arne
Published: June 2004

Studies have been made by means of sedimentation in the ultracentrifuge, and by diffusion and electrophoresis, to determine the molecular weights and homogeneity of the tuberculin protein and polysaccharide molecules as found in their natural state in the unchanged filtrates from culture media after growth of tubercle bacilli. These results have been compared with data obtained on fractions isolated by chemical procedures from them or from old tuberculin.

By means of electrophoresis in the Tiselius apparatus it was possible to separate the protein from the polysaccharide, as these two fractions occur naturally in the original culture medium filtrates of acid-fast bacilli.

The protein from the bovine strain of bacillus proved to be homogeneous in sedimentation (S20 = 1.6), diffusion (D20 = 12.0) and electrophoresis, with a molecular weight of about 10,000.

The tuberculin polysaccharide isolated in electrophoresis appeared to be practically the same in sedimentation and in precipitin reaction as the polysaccharide isolated by chemical procedure. The latter proved to be homogeneous in sedimentation (S20 = 1.6) and diffusion (D20 = 11.0) with a molecular weight of about 9000.

A practically homogeneous protein was isolated from the culture filtrate of the human tubercle bacillus H 37 by fractional ammonium sulfate precipitation, with a molecular weight of 32,000 (S20 = 3.3; D20 = 8.2). It was electrochemically homogeneous, with an isoelectric point at pH 4.3 and an isoionic point at pH 4.7. It could be dried or frozen with no loss in homogeneity. It was highly antigenic in the precipitin reaction and produced the anaphylactic type of local skin reaction in tuberculous guinea pigs, in contrast to the true tuberculin type of reaction caused by a purified PPD fraction. Furthermore death resulted in tuberculous guinea pigs from intracutaneous injection of exceptionally small amounts.

A protein with molecular weight of about 17,000 was isolated from the filtrate from cultures of the timothy bacillus.

The nucleic acid originally occurring in old tuberculin (OT) seems to be responsible for the high electrochemical mobility observed. From OT and the PPD made from it, potent but non-antigenic molecules of 16,000 and 9000 weight and with a low content of nucleic acid were isolated. With increase in size these deviated much from the normal compact spherical shape, and aggregation was evident from the tendency toward gel formation. The smallest molecule (9000) was homogeneous (S20 = 1.0; D20 = 10.0) and had lost some tuberculin potency.
RENAL FUNCTION AS AFFECTED BY EXPERIMENTAL UNILATERAL KIDNEY LESIONS
Authors: Nicholson T. F. , Urquhart R. W. I. , M.D. D. L. Selby
Published: June 2004

1. A method is described for the production of a nephrosis in one kidney of an experimental animal. The normal kidney in the same animal is available for a control.

2. The nephrosis produced by the injection of 7.5 per cent sodium tartrate is limited to the proximal convoluted tubule. There is no histological evidence of glomerular damage.

3. This damage results in a disturbance of water and chloride excretion as well as a decrease in the clearances of urea, xylose, inulin, creatinine and phenol red, and is observed under conditions of no diuresis, sugar diuresis and salt diuresis.

4. Excreted ferrocyanide is found in the cells of the proximal tubule of the damaged kidney. It is not present in these cells in the normal kidney. This is taken to be evidence of back diffusion of ferrocyanide through the damaged cells.

5. The decrease in clearance of creatinine and inulin, which in the dog represent glomerular filtrate, may therefore be explained by back diffusion and is not necessarily due to glomerular change.

6. The phenol red clearance from the damaged kidney is diminished in relation to inulin. This is further evidence of depressed tubular activity.
CHEMO-IMMUNOLOGICAL STUDIES ON CONJUGATED CARBOHYDRATE-PROTEINS
Authors: Goebel Walther F.
Published: June 2004

1. Artificial antigens containing the azobenzyl glycosides of the disaccharide cellobiose and the aldobionic acid, cellobiuronic acid, give rise in rabbits to antibodies which are specific and characteristic of the saccharide constituent. The antiserum to cellobiuronic acid shows broader serological cross reactions than does that to cellobiose.

2. An antiserum to the cellobiuronic acid antigen precipitates the capsular polysaccharide of Type III Pneumococcus when the latter is combined with a heterologous protein.

3. The cellobiuronic acid test antigen precipitates vigorously in antipneumococcus sera Types II, III, and VIII. The mechanism of these reactions is discussed.
ULTRACENTRIFUGATION STUDIES ON THE ELEMENTARY BODIES OF VACCINE VIRUS
Authors: Pickels Edward G. , Smadel Joseph E.
Published: June 2004

Ultracentrifugal studies on the CL dermal strain of vaccine virus indicate the following characteristics of the elementary bodies:—

1. A stable suspension of Paschen bodies in a dilute buffer solution of pH 6.2 to 8 sediments with the formation of a characteristic primary boundary which consistently shows a spread of approximately 14 per cent.

2. The principal sedimentation boundary is accompanied frequently by one or several more rapidly moving boundaries which probably are produced by groups of agglutinated elementary bodies consisting of two or more particles.

3. Occasionally the principal boundary may exhibit an irregular or peculiar behavior, a fact which necessitates a careful selection of material and the performance of many experiments for accurate interpretation of results.

4. The sedimentation constant of the slowest moving particles forming the principal boundary is computed to be 49.1 x 10–11 cm./sec./dyne. On the basis of this sedimentation rate, the average diameter of the smallest virus particles in appreciable amounts is estimated at 236 mµ. If the boundary spread is due principally to slight differences in particle size, then the largest single elementary bodies are approximately 252 mµ in diameter.
REACTIONS OF NORMAL AND TUBERCULOUS ANIMALS TO TUBERCULO-PROTEIN AND TUBERCULO-PHOSPHATIDE
Authors: Smithburn Kenneth C. , Sabin Florence R.
Published: June 2004

Prior observations on the cellular reactions to tuberculo-phosphatide are confirmed and compared with reactions induced by this material in tuberculous animals. In the latter the response is accelerated and augmented and simulates the Koch phenomenon.

Tuberculo-protein produces no macroscopic reaction in normal animals. The microscopic reaction of neutrophiles and monocytes regresses in less than a week. The same material in tuberculous animals causes a response characterized by more or less hemorrhage and necrosis, tissue degeneration, and infiltration of neutrophiles and monocytes. Late in the reaction there may be a few epithelioid cells and foreign body giant cells.

Preparations of tuberculo-phosphatide which contain no tubercle bacilli, or only a few, induce the typical cellular response but do not induce hypersensitiveness to tuberculin.

Repeated intradermal skin-test injections of tuberculo-protein MA-100 in normal guinea pigs may be followed by a mild hypersensitiveness to subsequent injections.
IMMUNOLOGICAL REACTIONS WITH A VIRUS CAUSING PAPILLOMAS IN RABBITS
Authors: Kidd John G.
Published: June 2004

The antigen that binds complement in the presence of sera neutralizing the Shope papilloma virus can be readily extracted from papillomas yielding infectious virus, but not from the normal skin of rabbits bearing the growths. The virus and the complement-binding antigen appear to have the same particle size, as determined by filtration, and they are thrown down together in the centrifuge. They are destroyed by the same amounts of heating and, in general, by the same changes in pH. It is possible, nevertheless, by irradiation with ultraviolet light, or by treatment with weak alkali, to render papilloma extracts non-pathogenic without diminishing their capacity to bind complement when mixed with immune serum.
IMMUNOLOGICAL REACTIONS WITH A VIRUS CAUSING PAPILLOMAS IN RABBITS
Authors: Kidd John G.
Published: June 2004

A study has been made of the yield of virus and of the complement-binding antigen from the virus-induced papillomas of cottontail and domestic rabbits. Extracts of the discrete, naturally occurring papillomas of cottontail rabbits usually contain virus in large amount; and, as a rule, they also contain the complement-binding antigen in high titer. The confluent growths produced experimentally with the virus in some cottontails, on the other hand, often fail to yield the virus, or furnish it in small amount; and extracts of them have little if any complement-binding capacity. The sera of cottontails with massive papillomas from which the virus cannot be recovered often have high antibody titers.

Many extracts were tested of the virus-induced papillomas of domestic rabbits. None contained the virus in large amount, and the majority of them failed to manifest it on sensitive test. A few fixed complement in low titer when mixed with immune sera, but most failed to do so. Crude extracts of the "non-infectious," virus-induced papillomas of domestic rabbits stimulated the formation of virus-neutralizing and complement-binding antibodies in low titer when injected intraperitoneally into normal rabbits of the same breed, but Berkefeld filtrates of the same materials proved devoid of this immunizing effect.

The significance of the findings described in the three papers is discussed. The evidence as a whole favors the view that the virus stimulates the formation of the virus-neutralizing and complement-binding antibodies in vivo, and many facts indicate that it is closely associated, and in all probability identical, with the antigen that reacts with immune serum to fix complement in vitro.
CELLULAR REACTIONS TO TUBERCULO-PROTEINS COMPARED WITH THE REACTIONS TO TUBERCULO-LIPIDS
Authors: Sabin Florence R.
Published: June 2004

1. Tuberculo-protein in solution induces the formation of monocytes in the normal animal and tubercles of epithelioid cells in that which is tuberculous.

2. Freshly precipitated tuberculo-proteins from the culture media and from the bacilli induce a moderate formation of epithelioid cells in normal animals, and more in the tuberculous.

3. Insoluble forms of tuberculo-protein induce complex tubercular tissue in normal animals. This action is enhanced in the tuberculous.
CELLULAR REACTIONS TO DEFATTED TUBERCLE BACILLI AND THEIR PRODUCTS
Authors: Sabin Florence R. , Joyner Austin L.
Published: June 2004

The cellular reactions to defatted tubercle bacilli are complex and like those to heat-killed whole tubercle bacilli.

The firmly bound lipid, when removed from these organisms, is non-acid-fast; it contains an hydroxy acid which is acid-fast and a polysaccharide, which is not.

This hydroxy acid gives rise to foreign body giant cells and the tissues eventually become infiltrated with eosinophiles.

The polysaccharides, both from the defatted bacilli and from the unfilterable lipid, call neutrophiles from the blood stream.

The reactions to the unfilterable lipid include those of both its constituents.
A STUDY OF HUMAN SKIN GRAFTED UPON THE CHORIO-ALLANTOIS OF CHICK EMBRYOS
Authors: Goodpasture Ernest W. , Douglas Beverly , Anderson Katherine
Published: June 2004

Human skin grafted upon the chorio-allantoic membrane of chick embryos adheres and becomes nourished for as long as 10 days. Occasionally regrafts upon a second egg have succeeded and thus prolonged the vitality of the graft to 14 days.

In successful experiments the epithelium of the chorio-allantois fuses with that of the graft, the collagen fibers of the corium interlace with those of the membrane after the separation or disappearance of the ectodermal layer, and the blood vessels of the chick anastomose, and unite by intervening pools of extravasated blood, with those of the graft. This vascular communication between the two tissues is largely responsible for the nourishment of the graft by affording a plasmatic circulation.

Gradually there is a partial revascularization of the graft by an ingrowth of blood vessels from the chick membrane.

Human skin grafts were susceptible to experimental infection by several viruses.
A NEOPLASM OF MONOCYTES OF MICE AND ITS RELATION TO SIMILAR NEOPLASMS OF MAN
Authors: Furth J. ,   With the Assistance of C. Breedis
Published: June 2004

A transmissible neoplasm of mice characterized by malignant cells resembling histiocytes (monocytes) is described. The morphology of these cells and the microscopic appearance of the lesions are similar to those of human neoplasms formed by histiocytes.

The malignant histiocytes form tumor-like masses in the liver and spleen and infiltrate these and other tissues. They are present in small numbers in the blood of many mice when the disease is far advanced. The malignant cells have scant phagocytic ability. The fixed cells of the host (endothelial cells and fibroblasts) have no significant part in the production of the lesions of the disease.

Transmission is readily accomplished when material containing the malignant histiocytes is used for inoculations, but fails in their absence. Attempts to demonstrate a cell-free transmitting agent have been unsuccessful.
THE LYMPHATIC PATHWAY FROM THE NOSE AND PHARYNX
Authors: Yoffey Joseph M. , Sullivan Eugene R.
Published: June 2004

Vaccinia virus dropped into the nose of a susceptible animal does not appear in cervical lymph in less than 12 hours. After 12 hours, and thereafter continuously for 7 days, a stream of virus is entering the blood through the cervical lymph ducts. Virus passes through the lymph nodes. Virus is fixed by the lymphocytes, and the significance of this is discussed.
THE SPECIFICITY OF KERATINS
Authors: Pillemer L. , Ecker E. E. , Wells J. R.
Published: June 2004

Kerateine and metakeratin were prepared from wool, chicken feathers and human hair. Chemical analyses revealed that the compounds are closely related.

The results of serological studies disclose that species specificity is an individual characteristic of the keratins employed and that the specificity observed is dependent on the redox state of the sulfhydryl groupings in the protein molecule.
THE RELATIONSHIP OF INFECTING DOSAGE, LEUCOCYTIC RESPONSE, BACTEREMIA, AND EXTENT OF PULMONARY INVOLVEMENT TO THE OUTCOME OF EXPERIMENTAL LOBAR PNEUMONIA IN THE DOG
Authors: Robertson O. H. , Fox John P.
Published: June 2004

The present study comprises observations on the course and outcome of experimentally produced Type I pneumococcus lobar pneumonia in dogs. It was found that within certain limits of dosage the outcome of the disease was closely related to the amount of culture and the volume of the starch inoculum employed. The much higher mortality rate resulting from simply increasing the volume of starch in which the pneumococci were suspended, appeared to be due chiefly to the greater area of lung tissue initially involved. Certain striking relationships were observed to exist between the leucocytic response, extent of pulmonary involvement, bacteremia and outcome. Marked changes in the number of white blood cells at end of the first 24 hours of the disease provided more valuable prognostic information than either the blood culture or the size of the lesion. Dogs showing high white counts at this stage seldom succumbed, while absence of leucocytosis and leucopenia were associated with a mortality which increased with the diminishing numbers of circulating white blood cells. Over 90 per cent of the animals with counts of less than 2,000 cells per c. mm. died. The extent of the pulmonary lesion was likewise observed to bear a direct relationship to death rate. With the lesion confined to a single lobe the mortality was only 1 per cent. Spread to other lobes was accompanied by a sharply rising death rate until it reached 98 per cent in dogs with three-fourths the lung field involved. Increasing occurrence of bacteremia paralleled both the decreasing white counts and the extending pulmonary lesions and subsequent to the 24 hour stage of the disease the presence or absence of pneumococci in the blood appears to be of more significance, in relation to outcome, than either of these two other factors. Even in the presence of leucopenia and an extensive lesion the animal might survive provided the blood remained sterile.
PHYSIOLOGICAL CONDITIONS EXISTING IN CONNECTIVE TISSUE
Authors: McMaster Philip D. , Parsons Robert J.
Published: June 2004

The escape of a vital dye from the lymphatics of the ears of living mice and its subsequent movement through normal and pathological connective tissue have been observed at high magnification. The dye first appears outside such channels as bristly, wavy lines of color, which can be bent and twisted by pressure with a micro probe and spring back to their original positions when the pressure is removed, as if the dye were fixed upon or between some tissue elements. Our findings indicate that this is the case, that the bristly lines of color are formed by dye moving between connective tissue fibers or along them. With the onset of mild edema, such as the dye induces secondarily, the bristles disappear, the coloration becoming diffuse and freely movable with the micro probe.

When edema is induced before dye is introduced into the lymphatics, the character of its escape is wholly different. It first appears as a colored cloud, freely movable in the edema fluid, the manner of its passage into the tissues being completely changed.

In the ears of mice partly dehydrated by bleeding, or in those of dead animals, the bristly or wavy lines were more evident than in normal individuals. It was plain that dehydration did not change the mode of transportation of the dye through the tissue but merely emphasized some of the characteristics of its passage. In animals injected intravenously with large amounts of physiological saline, with result in the presence of more tissue fluid than usual, the colored bristles were seldom seen.

It is plain that connective tissue fibers serve indirectly as pathways for the transport of substances of large molecule.

We have not been able by the dye method to demonstrate the presence of any free fluid in the normal tissues of the mouse ear.
HEMOGLOBIN PRODUCTION IN ANEMIA LIMITED BY LOW PROTEIN INTAKE
Authors: Hahn P. F. , Whipple G. H.
Published: June 2004

A low protein intake will cause limited hemoglobin production in standard anemic dogs. It appears that the dog on a limited protein intake is unable to produce the usual amount of globin and therefore of hemoglobin even in the presence of a large excess of iron.

Iron given by mouth or by vein shows the same result—the dog made anemic by blood withdrawal cannot produce the expected new hemoglobin related to the iron intake when the protein intake is held at low levels. These dogs can be kept in perfect health and weight equilibrium during these long periods of limited diet intake and anemia.

Under the stress of protein limitation the proteins of salmon muscle, banana and carrot are well utilized and it requires only 7 to 8 gm. of these food proteins to produce 1 gm. of new hemoglobin.

These experiments show clearly that the iron content of liver is not wholly responsible for its potency in anemia due to hemorrhage.
COMPLEMENT FIXATION IN HUMAN MALARIA WITH AN ANTIGEN PREPARED FROM THE MONKEY PARASITE PLASMODIUM KNOWLESI
Authors: Eaton Monroe D. , Coggeshall L. T.
Published: June 2004

In the studies of complement fixation described in this paper, the antigens were prepared from (a) normal monkey red cells, (b) parasitized red cells of monkeys dying with Plasmodium knowlesi infection, (c) the spleens of monkeys dying with Plasmodium knowlesi infection; the sera came from (a) normal human beings, (b) patients with syphilis, (c) patients with paresis who were receiving malaria therapy with Plasmodium knowlesi, Plasmodium vivax, or Plasmodium falciparum, and (d) patients with malaria alone.

The malarial antigens gave negative complement fixation reactions with 70 to 80 per cent of the luetic and normal sera and weak or doubtful reactions with the remaining 20 to 30 per cent. With the exception of one antigen prepared from spleen, there was no evidence that the malarial antigens were more reactive with Wassermann-positive than with Wassermann-negative sera.

Some human sera give weak complement fixation with antigens prepared from normal monkey erythrocytes, and the percentage of these positive reactions is slightly higher with malarial sera than with normal or luetic sera.

The most sensitive and specific malarial antigen was prepared from dried parasitized red cells by extraction with saline, freezing, and thawing. This P. knowlesi antigen gives strong complement fixation with malarial sera from human beings infected with P. knowlesi, P. vivax, or P. falciparum.

The titer of complement-fixing antibodies reaches a maximum about 1 month after the beginning of the acute infection. At this time all of the P. knowlesi sera tested were positive. After 4 months the reaction diminishes rapidly in titer but may remain positive for 12 months or longer. With P. knowlesi infections in man, the complement fixation reaction remains positive for some time after the infection has apparently disappeared as judged by daily smears and inoculation of monkeys with the blood.

The complement fixation reaction in malaria is group-specific rather than species-specific. Sera from patients infected with P. vivax or P. falciparum react in the same way with the P. knowlesi antigen as the homologous sera.

Absorption of malarial human sera with normal monkey erythrocytes does not remove the immune bodies which fix complement with malarial antigens.
A COMPARISON OF VIRUS-INDUCED RABBIT TUMORS WITH THE TUMORS OF UNKNOWN CAUSE ELICITED BY TARRING
Authors: Rous Peyton , Kidd John G.
Published: June 2004

Tarring the ears of rabbits of one sort with a single kind of tar evoked epidermal tumors of a few sharply defined types, namely ordinary papillomas, carcinoids, carcinomas, and "frill horns." These last, relatively infrequent, are now recognized for the first time. The carcinoids have proved to be the expression of a spurious malignancy of papillomas, resulting from intercurrent influences, and they were wholly dependent upon these for their threatening aspect and behavior. Chief amongst such influences was continued tarring. It had the effect of establishing the papillomas, stimulated their proliferation, complicated their morphology, and rendered some of them disorderly, aggressive, and anaplastic. It brought all of the tissues of the ears into an excitable state, and often this state endured long after the skin had apparently returned to normal.

The characters of the papilloma-carcinoids and of the frill horns were so different and distinctive as to imply the action of differing, specific causes.

The papillomas were very like those induced with the Shope virus, and hence a point-to-point comparison was made of their manifestations, including the derivation of carcinomas from them. This comparison demonstrated that the unknown cause of the tar papillomas provoked neoplastic phenomena which were identical in all essential respects with those due to the virus.

To suppose, for experimental purposes, that the papillomas which tarring elicits are caused by a virus rendered pathogenic by this procedure, is to demand least of the unknown. Yet it does not follow that they must be due to a virus.