bluuebunny/crossref_metadata_2025 huggingface dataset:
THE INFLUENCE OF DIET UPON THE REGENERATION OF SERUM PROTEIN
Authors: Melnick Daniel , Cowgill George R. , Burack Ethel
Published: June 2004

1. By the technique of quantitative plasmapheresis the effects of single proteins in artificial synthetic diets were studied with respect to their value in promoting the regeneration of serum protein.

2. The ratio of (a) the amount of serum protein per week removed by bleeding above that regenerated by the dog when eating the protein-free diet, to (b) the dietary protein increment (i.e., above that required for nitrogen equilibrium) was termed the potency ratio. The results indicated that serum protein was slightly superior to casein and lactalbumin in promoting the regeneration of serum protein. However, the respective potency ratios, varying from approximately 0.51 to 0.36, were comparable and not widely divergent as those reported by others. It was concluded that, whereas in some individuals dietary proteins may be able to produce a significant increase in the serum protein concentration, the potency ratios are not sufficiently different to warrant the administration of any one protein in preference to another.

3. The inhibitory effect of the basal protein-free diet with respect to serum protein regeneration in the dog was also demonstrated by the inability of the protein concentration to attain the normal level in spite of discontinued plasmapheresis. However, a subsequent fasting period resulted in a progressive rise in the serum protein concentration until the normal value was approximated. These observations are interpreted as indicating that the products of tissue protein catabolism can be utilized in the formation of new serum protein.

4. The experimental production of what seems to be an inhibition of the serum protein regenerating mechanism was described. This observation together with the hypothetical evidence presented by Bloomfield (17) and Weech and his associates (9) suggests that the most profitable line of approach to solution of the problem of hypoproteinemia lies not so much in the evaluation of dietary factors but in finding a way for stimulating internally the serum protein regenerating mechanism, which seems to involve in some manner the capacity of the tissue to furnish protein for the needs of the plasma.

5. A hypothesis explaining the mechanisms responsible for serum protein formation was presented and the experimental support for it discussed. The rôle of tissue protein catabolism in this function was emphasized.
AN ANALYSIS OF MITOSIS IN LIVER RESTORATION
Authors: Brues Austin M. , Marble Beula B.
Published: June 2004

1. Following partial hepatectomy in the rat, there is a latent period of 1 day during which the rapidly growing organ shows no increase in cell number. Mitosis then begins rapidly, following a brief pre-mitotic period of visible nuclear changes.

2. It can be shown that the increase in cell number during the ensuing 48 hours follows a formula of the type dN/dt = ke-kt., beyond this time it is retarded more than this simplified formula would predict. The average mitosis rate at 1, 2, and 3 day intervals after operation follows the same formula; from this the duration of each mitosis is calculated to be about 49 minutes. It is not necessary to assume that amitotic division plays an important part, and no such divisions have been seen by the writers.

3. The percentage of cells in mitosis in a single hypertrophying liver varies widely from hour to hour, so that a single mitosis count tells nothing about the growth rate. The fluctuations occur at different times in different livers. It appears that no great number of mitoses begin or end simultaneously.

4. Mitoses are evenly distributed throughout the liver and throughout each lobule; there is no preponderance near the bile duct cells.

5. The mean initial mitosis rate (at 24 hours after operation) is 2.13 per cent, and it diminishes from then on. This rate is very similar to that in early embryo heart and tissue cultures of mesenchyme. In individual specimens the rate can be over 8 per cent. This rapid rate occurs without signs of cell dedifferentiation.
THE CAPILLARY SUPPLY IN NORMAL AND HYPERTROPHIED HEARTS OF RABBITS
Authors: Shipley R. A. , Shipley Louise J. , Wearn Joseph T.
Published: June 2004

1. During normal growth of the rabbit heart, muscle fibers enlarge, and the capillaries multiply so that a relatively constant capillary supply per unit of tissue is maintained from the time of birth to maturity.

2. In cardiac hypertrophy the muscle fibers enlarge, but the capillaries do not multiply and, as a result, the capillary supply per unit of tissue is reduced.

3. The decreased concentration of capillaries in the hypertrophied heart would constitute an impediment to the adequate exchange of metabolic substances, but the seriousness of the impediment cannot be estimated without further physiological data.
STUDIES ON THE SOMATIC C POLYSACCHARIDE OF PNEUMOCOCCUS
Authors: Abernethy Theodore J. , Francis Thomas
Published: June 2004

A study of 46 cases of pneumococcus pneumonia has shown that a characteristic response may be elicited by the intracutaneous injection of 0.1 mg. of the somatic C polysaccharide of pneumococcus. During the acute febrile period in patients who recover, the response consists of a delayed erythema which reaches its maximum intensity in 18 to 24 hours. During convalescence the reaction is not demonstrable. In patients in whom the disease is prolonged by complications the capacity of the skin to react persists. In 7 fatal cases the skin failed to react to C polysaccharide.

Parallel studies of the reaction of the patients' serum with C have confirmed and extended the observations of Tillett and Francis on the appearance of the precipitation phenomenon during the acute stages and its disappearance in recovery.

That the cutaneous and serological reactions are not specific for pneumococcus infection is shown by the results in 29 control cases. 8 patients with infectious febrile diseases not of pneumococcus origin gave responses similar to those noted in pneumonia. 2 patients with non-infectious fevers and 18 of 19 normal individuals failed to give either skin or serum reactions.

These observations emphasize the importance of using separate components of the bacterial cell in the interpretation of cutaneous and serological reactions in pneumonia. The parallelism in results of the skin and serum tests in pneumococcus pneumonia with the somatic carbohydrate C, the significance of the reactions in relation to the clinical course and outcome of the disease, and the frequency of occurrence of both reactions in bacterial infections other than those of pneumococcal origin, are discussed.
THE PRODUCTION OF BLOOD PLATELETS IN THE LUNGS
Authors: Howell W. H. , Donahue D. D.
Published: June 2004

1. A new fixing solution is described, which preserves the platelets and prevents contact hemolysis of the erythrocytes, so that counts of both corpuscles may be made in the same preparation.

2. Comparative counts of platelets in arteries and veins show that arterial blood contains a larger number of platelets than venous blood. This difference is accentuated under experimental conditions that cause a reduction in the number of platelets. It is concluded that new platelets are added to the blood in the capillary areas of the lungs, and that there is a corresponding destruction of platelets as the blood passes through the capillary areas of the systemic circulation.

3. Perfusion of the lungs with a platelet-preserving solution, compared with that of other organs, gives evidence of the existence of a source of platelet material in the lungs.

4. Histological examination of the lungs with a technique adequate to give a differential staining of platelet material demonstrates the presence of giant cells in the lungs, and supports the view that they are active in the production of platelets.

5. In extrauterine life giant cells are concentrated in the marrow and the lungs, with the maximum of their activity in platelet production in the lungs.
IMMUNIZATION OF RABBITS TO INFECTIOUS PAPILLOMATOSIS
Authors: Shope Richard E.
Published: June 2004

Two intraperitoneal injections of either infectious or non-infectious rabbit papilloma suspensions actively immunize rabbits against papillomatosis. The capacity of the non-infectious suspensions to immunize is considered as evidence that they contain papilloma virus even though none can be demonstrated by the usual infection test.
IMMUNOLOGICAL AND CHEMICAL INVESTIGATIONS OF VACCINE VIRUS
Authors: Parker Robert F. , Rivers Thomas M.
Published: June 2004

A method has been described by which a stable, serologically active substance has been isolated in a relatively pure state from tissues infected with vaccine virus. It has the characteristics of an alcohol-soluble protein which is not precipitated by boiling in a neutral aqueous solution. In a dilution of 1:640,000 it gives a precipitate when mixed with a serum containing antibodies against Craigie's S antigen of vaccine virus, but no visible reaction occurs when it is mixed with serum depleted of S antibodies by means of absorption.
STUDIES ON MENINGOCOCCUS INFECTION
Authors: Alexander H. E. , Rake Geoffrey
Published: June 2004

Precipitin tests have been carried out on spinal fluid from cases of meningococcal and other forms of meningitis, with monovalent anti-meningococcus horse serum of high titer. Using such a test it has been possible within 2 hours to diagnose and type cases of Type I and Type II meningococcal meningitis. In a certain number of cases fluids which were negative when first drawn became positive after standing for 1 or 2 days at 37°C. or room temperature. In 9.5 per cent of all Type I cases the fluids did not become positive. Fluids from cases due to atypical meningococci may react with the type serum of the group to which they belong (i.e., Types II* and VII, which belong to group II, with Type II serum) but do not in every case. Fluids from forms of meningitis other than meningococcal give no reaction. The use of concentrated sera is not advantageous at present, owing to the heterologous reactions which occur.
ANAPHYLACTIC SENSITIZATION WITH CHEMICALLY DEFINITE COMPOUNDS
Authors: Fierz H. E. , Jadassohn W. , Stoll W.
Published: June 2004

Injection of sodium atoxyl-diazoamino-sulfoanthranilate into guinea pigs produces an anaphylactic hypersensitiveness to the corresponding azoprotein (Schultz-Dale test). This leads to the conclusion that the injected sodium atoxyl-diazoamino-sulfoanthranilate first decomposes and then couples in vivo with the body protein to form the corresponding azoprotein and that therefore it is this compound, produced within the organism itself, which sensitizes.
THE LYMPHATICS AND LYMPH FLOW IN THE EDEMATOUS SKIN OF HUMAN BEINGS WITH CARDIAC AND RENAL DISEASE
Authors: McMaster Philip D.
Published: June 2004

Local intradermal injections of dye have disclosed the fact that the skin lymphatics in regions of cardiac edema are patent, full of fluid and much widened. Intercommunication between them is ready and dye escapes from them more rapidly than from the vessels of normal skin. A retrograde distribution of dye by way of the lymphatics often occurs and it may pass unseen along the deeper channels to emerge in the skin at unexpected, distant situations. A valvular incompetence of the lymphatics consequent on dilatation would appear to be the cause of these phenomena. In regions of cardiac edema lymph stagnates, despite the fact that the channels are open.

In nephritic edema the lymphatic capillaries are wider than normal but not as wide as in cardiac edema. No sign of incompetency of the valves is to be observed. Instead lymph flow is considerably greater than normal, even when edema fluid is accumulating. It was noted to be greater in the periods of fluid equilibrium also and extraordinarily rapid in periods of diuresis.
THE MOLECULAR WEIGHT OF ANTIBODIES
Authors: Heidelberger Michael , Pedersen Kai O.
Published: June 2004

1. Highly purified rabbit Type III pneumococcus anticarbohydrate proved to be homogeneous in the ultracentrifuge and its sedimentation constant, 7.0·10–13, did not differ from that of the principal component of normal rabbit globulin or of immune rabbit globulin containing up to 50 per cent of anti-egg albumin. The molecular weight of antibody in the rabbit is therefore probably very close to that of the principal normal globulin component, namely, 150,000.

2. Highly purified horse Type I pneumococcus anticarbohydrate, on the other hand, was only homogeneous in the ultracentrifuge when prepared from sera stored without preservative. Its sedimentation constant, 18.4·10–13, coincided with that of the principal globulin component in most of the Felton solutions and purified antibody solutions studied. The molecular weight of pneumococcus anticarbohydrate in the horse is probably three to four times that of the principal normal globulin component.

3. The significance of the differences between pneumococcus anticarbohydrate formed in the rabbit and in the horse is discussed.

4. Results are given of ultracentrifuge studies on the molecular species in solutions of egg albumin-anti-egg albumin specific precipitates dissolved in excess egg albumin. The implications of the results are discussed.
ANTIDIURETIC PITUITARY SUBSTANCE IN BLOOD, WITH SPECIAL REFERENCE TO THE TOXEMIA OF PREGNANCY
Authors: Melville K. I.
Published: June 2004

A method is described for the quantitative extraction of posterior pituitary antidiuretic substance from blood with which it has been mixed in vitro and in vivo for experimental purposes.

With this procedure, it is found that a similarly extractable active substance may be detected as a normal constituent of dog and human blood.

The data obtained from the blood of normal pregnancies and several cases of early toxemia, do not indicate any causal relationship between the presence of this substance in the circulating blood and the early symptoms (hypertension, edema, albuminuria) of the toxemia of pregnancy.
LIVER FUNCTION AND BLOOD PLASMA PROTEIN FORMATION
Authors: Knutti R. E. , Erickson C. C. , Madden S. C. , Rekers P. E. , Whipple G. H.
Published: June 2004

Normal dogs and two Eck fistula dogs, receiving a daily diet containing an average of 1 gm. of vegetable protein per kilo of body weight, showed after average intervals of 7 to 9 weeks, slight decreases in amounts of circulating plasma protein (Table 21).

A third Eck fistula dog under similar circumstances was unable to maintain its plasma protein concentration above the edema level. This dog by biopsy was shown to have an abnormal liver and the evidence indicated that the other organs were normal. The animal showed active thirst and diuresis as compared with controls (Table 25).

This Eck fistula dog had less than one-tenth the capacity of the normal dog to form new plasma protein when various food proteins were added to the basal diet, and no significant quantitative differences in the relative potency of these foods (liver, kidney, heart muscle, soy bean, salmon) could be distinguished (Table 22).

It appears that the liver abnormality is responsible for this abnormal reaction. This observation gives strong support to the thesis that the liver is actively concerned with fabrication of new plasma protein.
AN IMPROVED AIR-DRIVEN TYPE OF ULTRACENTRIFUGE FOR MOLECULAR SEDIMENTATION
Authors: Bauer Johannes H. , Pickels Edward G.
Published: June 2004

1. A description is given of the construction details and operation characteristics of an improved type of air-driven ultracentrifuge operating in vacuum and suitable for the determination of sedimentation constants of protein molecules.

2. The rotor of the centrifuge is made of a forged aluminum alloy; it is oval in shape, measures 185 mm. at its greatest diameter, and weighs 3,430 gm. It carries a transparent cell located at a distance of 65 mm. from the axis of rotation and designed to accommodate a fluid column 15 mm. high.

3. The rotor has been run repeatedly over long periods at a speed of 60,000 R.P.M., which corresponds to a centrifugal force of 260,000 times gravity in the center of the cell. At this speed no deformation of the rotor nor leakage of the cell has been observed.

4. The sharp definition of sedimentation photographs taken at high speed serves to indicate the absence of detectable vibrations in the centrifuge.

5. When a vacuum of less than 1 micron of mercury is maintained in the centrifuge chamber, the rise in the rotor temperature amounts to only 1 or 2°C. after several hours' run at high speed.

6. There has been no evidence of convection currents interfering with normal sedimentation of protein molecules in the centrifugal field.

7. A driving air pressure of about 18 pounds per square inch is sufficient to maintain the centrifuge at a steady speed of 60,000 R.P.M. With a driving pressure of 80 pounds per square inch, it can be accelerated to this speed in less than 20 minutes, and also brought to rest in about the same length of time by the application of the braking system.

8. The adaptation of Svedberg's optical systems to this centrifuge for photographically recording the movement of sedimentation boundaries is described.
ELECTROPHORESIS OF PURIFIED ANTIBODY PREPARATIONS
Authors: Tiselius Arne
Published: June 2004

Electrophoretic mobilities of antibody preparations isolated from type specific antipneumococcus horse and rabbit sera, measured over a range of pH values, show that these preparations are distinctly different from normal serum proteins in their electrochemical properties.
A QUANTITATIVE THEORY OF THE PRECIPITIN REACTION
Authors: Heidelberger Michael , Kendall Forrest E.
Published: June 2004

1. The reaction between the specific polysaccharide of Type III pneumococcus and homologous antibody in rabbit sera is quantitatively accounted for by expressions similar to those derived from the mass law for the corresponding horse sera. Preliminary data are also given for the Type I reaction.

2. Differences and similarities of the reaction with antibodies produced by the two animals are discussed.

3. Calculations are made of the equivalent composition of the specific precipitate at various reference points in the reaction range.

4. Certain theoretical and practical implications of the findings are pointed out.
THE EFFECT OF PROLONGED CULTIVATION IN VITRO UPON THE PATHOGENICITY OF YELLOW FEVER VIRUS
Authors: Theiler Max , Smith Hugh H.
Published: June 2004

1. Experimental evidence is presented to show that prolonged cultivation of yellow fever virus in vitro results in a change in its pathogenicity, and that this change varies with the type of tissues used for the cultivation.

2. In the tissue cultures used for the propagation of the virus, three different types of tissues were used. They included whole mouse embryo, chick embryo from which the head and spinal cord had been removed, and testicular tissues of mice and guinea pigs.

3. The changes in the pathogenicity of the virus cultivated for a period of over 3 years in a medium containing the tissues of whole mouse embryo were not striking. The viscerotropic virulence of the virus appeared somewhat diminished, in that when injected subcutaneously into rhesus monkeys or hedgehogs it failed to produce a fatal infection, although there is evidence to indicate that a generalized infection takes place as demonstrated by the appearance of virus in the circulating blood in relatively high concentration during infection. The neurotropic virulence of the virus remained unaltered during the cultivation in this medium.

4. The changes in the pathogenicity of the virus cultivated in medium containing tissues of chick embryo from which the head and spinal cord had been removed were very pronounced. The viscerotropic virulence of the virus was lost to a large extent. When injected subcutaneously into monkeys there was as a rule a very mild generalized infection, as demonstrated by the minimal quantities of virus found in the circulating blood. Its neurotropism was also much diminished. When injected into monkeys intracerebrally, it no longer produced a fatal encephalitis but only a moderate febrile reaction, followed by recovery and solid immunity to reinoculation with a highly virulent strain of virus. When injected intracerebrally into mice, the mortality ratio was not diminished but the incubation period was markedly prolonged.

5. The changes in the pathogenicity of the virus cultivated in medium containing testicular tissues were somewhat similar to those observed after cultivation in chick embryo medium which contained only a minimal amount of nervous tissue. Its viscerotropic affinity had been largely lost and only very small amounts of virus were found in the circulating blood of monkeys inoculated subcutaneously. Given intracerebrally, it produced death from encephalitis in monkeys. The incubation period in mice inoculated intracerebrally with this virus was also prolonged but somewhat less so than with the virus grown in chick embryo tissues without the central nervous system.
THE USE OF YELLOW FEVER VIRUS MODIFIED BY IN VITRO CULTIVATION FOR HUMAN IMMUNIZATION
Authors: Theiler Max , Smith Hugh H.
Published: June 2004

The response of rhesus monkeys to a subcutaneous inoculation with varying amounts of virus modified by prolonged cultivation in vitro has been studied. The tissue components of the medium consisted of chick embryo tissue containing minimal amounts of nervous tissue.

The immunity produced in monkeys, as measured by the antibody titer developed, has no relation to the amount of virus inoculated.

Monkeys inoculated subcutaneously with the tissue culture virus are rendered immune to a subsequent injection of a highly virulent yellow fever virus. This resistance is already present 7 days after vaccination.

The subcutaneous inoculation of the culture virus into immune persons leads to a substantial increase of the serum antibody titer.

The results of vaccinating eight normal persons with culture virus are presented. The reactions were minimal. The highest temperature recorded following vaccination was 37.4°C.

The sera taken from the eight vaccinated persons 2 to 4 weeks after inoculation with the tissue culture virus showed the presence of yellow fever antibodies.
THE ADAPTATION OF UNMODIFIED STRAINS OF YELLOW FEVER VIRUS TO CULTIVATION IN VITRO
Authors: Smith Hugh H. , Theiler Max
Published: June 2004

1. In a search for suitable tissues for the cultivation of yellow fever virus in vitro, mouse embryos were inoculated with this virus in utero. A titration for virus content of the various organs of the embryos indicated that the virus was present in the brain in greatest concentration.

2. Unmodified strains of yellow fever virus were readily adapted to cultivation in vitro in a medium consisting of minced mouse embryo brain tissue and Tyrode solution containing 10 per cent normal monkey serum.

3. After a continued cultivation in mouse embryo brain tissue cultures for twenty to twenty-five subcultures, these strains were readily adapted to cultivation in whole mouse embryo tissue medium.

4. There is evidence to indicate that a prolonged cultivation of the virus in mouse embryo brain medium increases its neurotropic properties.

5. Attempts to employ monkey tissues for in vitro cultivation of yellow fever virus gave entirely negative results.
TOXEMIA OF PREGNANCY IN THE RABBIT
Authors: Greene Harry S. N.
Published: June 2004

The clinical manifestations and pathology of a disorder associated with pregnancy in the rabbit have been described. The disorder bears a close analogy to toxemia of pregnancy in man and offers an experimental approach to the problems associated with that condition. The evidence at hand indicates that the disorder is of endogenous origin and arises from a disturbance of functions concerned in reproductive processes.
INFECTIOUS CATARRH OF MICE
Authors: Nelson John B.
Published: June 2004

A natural outbreak of an infectious catarrh in a colony of Swiss mice is reported. The disease was generally characterized by a peculiar chattering sound during life and by a rhinitis, an otitis media, and a pneumonia at autopsy. The pneumonia was slowly progressive and terminated fatally in a high percentage of cases. The mortality in a group of 75 naturally infected mice was 95 per cent over a period of 11 months.

The disease was readily reproducible in susceptible mice by the nasal instillation of exudate from any locus of infection. It was also transmissible by direct contact. In both naturally and experimentally infected animals there was an incubation period of 10 days or more before symptoms were apparent. Recovery from the disease was not observed.
THE ACTION OF IMMUNE SERUM ON HUMAN INFLUENZA VIRUS IN VITRO
Authors: Magill T. P. , Francis Thomas
Published: June 2004

Studies have been conducted on the effect of immune serum upon a strain of human influenza virus (PR8) grown in chick embryo tissue culture medium. The results have demonstrated (a) that when cells are exposed to the action of immune serum of high titer and subsequently washed freely, these cells support the growth of virus as well as cells treated with normal serum; (b) that, in agreement with the results of other workers, when virus is added to cell suspensions before the addition of immune serum of low titer, virus survives in the cells; (c) that when mixtures of immune serum of low titer and virus are added to cells, there is little evidence of survival or multiplication of the virus. Furthermore, when immune serum of high titer is used the virus is inactivated regardless of whether the cells are first exposed to virus or immune serum. Finally, virus mixed with a strong immune serum is inactivated in the absence of cells, as shown by the fact that centrifugation at high speeds of such serum-virus mixtures yields no active virus, whereas normal serum-virus mixtures yield fully active virus.
THE MULTIPLICATION OF THE VIRUS OF YELLOW FEVER IN AËDES AEGYPTI
Authors: Whitman Loring
Published: June 2004

Aëdes aegypti have been shown to be capable of multiplying the Asibi strain of yellow fever virus in their bodies. Following the ingestion of infected blood, the content of virus falls for several days, reaching a minimum during the 1st week. It then increases rapidly until quantities of virus greater than those previously encountered can be demonstrated. The actual final amount of virus demonstrable, however, is subject to variations of which we know little.
IMMUNOLOGICAL RELATIONSHIP BETWEEN THE SWINE AND HUMAN INFLUENZA VIRUSES IN SWINE
Authors: Shope Richard E.
Published: June 2004

Swine recovered from infection with either swine influenza or swine influenza virus alone are usually not only immune but refractory to human influenza infection. Swine recovered from infection with a mixture of human influenza virus and H. influenzae suis are usually immune to swine influenza while those recovered from infection with human influenza virus alone are usually not immune to swine influenza. The possible mechanisms involved in the cross-immunity between the influenza viruses are discussed.
DEMONSTRATION OF PASSIVE IMMUNITY IN EXPERIMENTAL MONKEY MALARIA
Authors: Coggeshall L. T. , Kumm H. W.
Published: June 2004

A Plasmodium knowlesi infection in rhesus monkeys is almost invariably fatal. This infection, however, may be made chronic by the early administration of antimalarial drugs. The animals then will harbor a chronic infection for an indefinite period. The serum taken from monkeys with chronic infection and injected into those suffering from an acute attack was found to have a definite depressing effect upon the course of the experimental disease. In some instances death was prevented and the acute infection changed into a chronic form; in others, the course of the experimental disease was prolonged.

In a similar manner the serum from monkeys harboring a chronic Plasmodium inui infection, when injected into monkeys suffering from an acute attack due to this parasite, was found to be effective in reducing the intensity of the primary infection.

The data presented indicate that protective antibodies are produced in the serum of monkeys during experimental malaria infection.
STUDIES ON THE PHYSIOLOGICAL CONDITIONS PREVAILING IN TISSUE CULTURES
Authors: Zinsser Hans , Schoenbach Emanuel B.
Published: June 2004

An analysis of some of the physiological factors active in Maitland tissue cultures has been presented in the hope that it may be of some value in clarifying the principles underlying tissue cultures in general.

It has been found that the empirically determined necessity of using relatively small amounts of tissue in such cultures is dependent upon the fact that excessive tissue leads to a rapid change of reaction toward the acid side. Whereas tissue may remain viable in an environment as alkaline as pH 9 and over, viability is rapidly destroyed when the reaction approaches pH 6.

Evidence is presented to indicate that the changes in electrode potentials which take place in Maitland cultures are not, as has been suggested, the determining factors upon which virus multiplication depends, although they may, of course, be incidentally important.

It has been shown that there are fundamental differences between those conditions in Maitland cultures which favor the multiplication of a typical virus and those upon which the growth of the Rickettsiae of typhus fever depends.

The virus which we have studied (equine encephalitis virus, western type) multiplies during the period of active tissue metabolism. The maximum virus titrations are obtained at about the time at which metabolism has come to a standstill. Thereafter the virus not only ceases to increase but rapidly deteriorates. The period of viability of the tissue cells themselves is shortened by several days in the presence of virus multiplication. There is some evidence that a temporary acceleration of oxygen uptake takes place during the time of active virus multiplication. Technical difficulties in controlling such experiments prevent certainty in regard to this point.

In contrast with the conditions determining the growth of a virus agent in the Maitland cultures the multiplication of Rickettsiae does not begin to any determinable extent until after active cell metabolism has either become stabilized or has ceased. The Rickettsiae continue to grow at a time when the cells are no longer viable. It appears likely that these organisms find the most favorable conditions for growth in cells which are no longer metabolically active but in which some delicately heat-susceptible elements have not yet been disturbed. As a consequence of these observations, frozen and preserved embryonic tissues have been successfully used for Rickettsia cultivation. A report on these experiments will be made in a separate communication.
A QUANTITATIVE THEORY OF THE PRECIPITIN REACTION
Authors: Kabat Elvin A. , Heidelberger Michael
Published: June 2004

1. The reaction between crystalline horse serum albumin and homologous antibody in rabbit sera is quantitatively accounted for by expressions similar to those derived from the law of mass action for other immune precipitating systems.

2. The reaction of an azo dye prepared from crystalline serum albumin by coupling with diazotized R-salt-azo benzidine was also studied with homologous antibody and anti-serum albumin.

3. Quantitative data obtained on cross reactions with the two antigens differ markedly from data on the corresponding reactions in the egg albumin system and indicate that tyrosine and perhaps histidine, while important in determining the serological specificity of egg albumin, have little connection with the specificity of serum albumin.

4. Calculations are made of the equivalent composition of the specific precipitate at various reference points in the reaction range.
A QUANTITATIVE THEORY OF THE PRECIPITIN REACTION
Authors: Stokinger Herbert E. , Heidelberger Michael
Published: June 2004

1. Quantitative data for both homologous and heterologous precipitin reactions of human, hog, beef, and sheep thyroglobulins show that these reactions have the same mechanism as other instances of the precipitin reaction and may be expressed quantitatively by the same equations derived from the law of mass action.

2. It is shown that all of the added antigen is precipitated in the region of antibody excess and in the equivalence zone, so that in these portions of the reaction range the composition of the specific precipitate may be calculated from the nitrogen precipitated and the amount of antigen nitrogen added.

3. The thyroglobulin-antibody reaction is characterized by low antibody N to antigen N ratios, as would be expected with an antigen of high molecular weight. Molecular ratios varying from 60:1 to 1:1 were calculated for the extremes of the reaction range, indicating a very large number of immunologically reactive groupings on the thyroglobulin molecule.

4. Failure of thyroxine or diiodotyrosine to inhibit specific precipitation was confirmed, but it is shown that this need not mean that these substances do not occur in thyroglobulin, as has been claimed.
VARIATION IN THE SIZE OF TRANSPLANTS OF THE PROSTATE AND SEMINAL VESICLE IN THE ANTERIOR CHAMBER OF THE EYE
Authors: Moore Robert A. , Rosenblum H. B. , Tolins S. H. , Melchionna Robert H.
Published: June 2004

1. A method is described with which the two-dimensional size of a transplant in the anterior chamber of the eye may be measured daily with a high degree of accuracy.

2. The size of transplants of the prostate and seminal vesicles varies from day to day and objective evidence indicates that this variation is related to physiologically active testicular tissue.
THE RELATION OF BLOOD CHOLESTEROL AND THE SIZE OF PROSTATIC AND VESICULAR TRANSPLANTS IN THE ANTERIOR CHAMBER OF THE EYE
Authors: Moore Robert A. , Smith J. J.
Published: June 2004

In male rabbits, injections of the female sex hormone result in marked increase in the size of ocular transplants of the prostate and seminal vesicles and a correlated elevation of the blood cholesterol.

Other hormones, which cause an increase in the size of the transplants, do not show this correlation.

The ingestion of cholesterol with conspicuous increase of the blood cholesterol, has no effect on the size of the transplants.
THE CULTURE OF WHOLE ORGANS
Authors: Okkels Harald
Published: June 2004

1. During the 1st and 2nd day of cultivation of the whole thyroid gland in the Lindbergh apparatus, perfused by a medium containing 20 or 40 per cent homologous serum diluted with glucose-Tyrode, the state of the thyroid epithelium remains histologically normal and even the most delicate cytological details retain their normal aspect.

2. Cultivation over a period up to 6 days need not cause any serious histological alteration of the gland; but cytological examination reveals an increasingly damaged condition of the mitochondria and the Golgi apparatus. These changes seem not to interfere with the life of the cells, however; epithelial culture from the perfused organs yields positive results.

3. The process of cultivation is liable to cause a slight morphological reaction in the thyroid epithelium, which resembles a feeble stimulation of the tissue.

4. Addition of the thyro-stimulating factor from the anterior pituitary to the perfusion fluid causes a stimulation of the cultivated thyroid epithelium which is comparable to, but not so marked as, the corresponding reaction in the living animal.
STUDIES ON PULMONARY EDEMA
Authors: Farber Sidney
Published: June 2004

1. Guinea pigs die shortly after bilateral cervical vagotomy, even when continuous artificial respiration effected through a tracheal cannula is carried out. Death is caused by severe pulmonary edema and congestion.

2. Direct observation of the lungs after bilateral vagotomy demonstrates that pulmonary edema develops gradually and increases slowly in amount and severity. Congestion precedes and accompanies the development of the edema.

3. Neuropathic pulmonary edema in the guinea pig is caused by disturbance to or abolition of the pulmonary vasomotor nerves.

4. The evidence obtained by experiments on animals suggests that neuropathic pulmonary edema in man is caused by disturbances, either central or peripheral, to the vasomotor control of the pulmonary vessels.
ON THE MODE OF ACTION OF SULFANILAMIDE IN EXPERIMENTAL STREPTOCOCCUS EMPYEMA
Authors: Gay Frederick P. , Clark Ada R.
Published: June 2004

Sulfanilamide prevents the evolution of an invariably fatal streptococcus empyema in rabbits when it is given repeatedly and in sufficient doses subcutaneously. Complete sterilization of the inoculated cavity occurs on approximately the 2nd day. The serum, defibrinated blood and artificial pleural exudate of similarly treated animals inhibits the growth of the same streptococcus in the test tube but even repeated doses of such treated blood serum fail to sterilize the culture. The coccal chains grown in such drugged serum are elongated and present pleomorphic and metachromatic organisms and may give rise to colonies that are at first less predominantly mucoid in appearance. Such organisms have, however, lost little if any of their virulence.

Cooperation on the part of locally derived clasmatocytes is apparently required in complete sterilization of the animal body. This conclusion is reached not only by a process of exclusion from comparison with the test tube results, but through the direct histological demonstration of a precocious and increasing mobilization of clasmatocytes in the parietal and visceral pleura of treated animals.

In other words, sulfanilamide apparently produces a bacteriostasis sufficiently marked to protect the accumulated leucocytes and to allow the natural defense macrophages to accumulate. There is direct evidence that the drug does not in itself stimulate the mobilization of the macrophages. There is no evidence that the cell reaction which finally accounts for disposal of the organisms is other than local.
GLOBIN UTILIZATION BY THE ANEMIC DOG TO FORM NEW HEMOGLOBIN
Authors: Robscheit-Robbins F. S. , Whipple G. H.
Published: June 2004

It has been shown that the standard anemic dog can use sheep, goose or dog hemoglobin when given by vein and return quantitatively its equivalent as new dog hemoglobin within the red cells.

Globin at times can be used when given by vein with a quantitative return of new hemoglobin in red cells in these same anemic dogs. Again the administration of globin by vein will inhibit the expected hemoglobin formation; and we believe the toxic effect of the globin is responsible. A digest of globin may be used by the anemic dog to form new hemoglobin. Globin from both horse and dog have been tested and seem to react in identical fashion.

The globin radicle of hemoglobin appears to be an important limiting factor in abundant hemoglobin building in this type of anemia due to blood loss.

Globin fed by mouth is well utilized to form new hemoglobin and we may record a 30 to 40 per cent utilization or a return of 30 to 40 gm. new hemoglobin from the feeding of 100 gm. globin. This is to be compared with the utilization of liver protein—an average return of 13 gm. new hemoglobin for the feeding of 100 gm. liver protein.
THE COMPARATIVE EFFECTS OF NEUTRONS AND X-RAYS ON THE WHOLE BODY
Authors: Lawrence John H. , Tennant Robert
Published: June 2004

Irradiation of the whole bodies of mice with neutron rays in sufficient quantities, leads to a clinical, bacteriological and anatomical picture similar to that following Roentgen irradiation. The mucosa of the small intestine and the lymphoid and hemapoietic tissues are the most radiosensitive. The mechanism of death after both forms of radiation seems to be a combination of tissue destruction and enterogenous infection, the former predominating in the acute deaths after large doses. Aside from any possible delayed effects from exposure to small doses over a long period of time, concerning which we have no information, these changes after relatively large doses make it imperative that workers in laboratories generating neutrons protect themselves from exposure by screening. For the same amount of ionization measured by a small bakelite-walled thimble chamber, neutrons are more biologically destructive than x-rays. The average daily dose to those working with neutrons should not exceed one-fourth of the tolerance dose accepted for x-rays. Whether daily doses of this magnitude, over a long period of time, will result in damage is not known. Also, if neutrons are tried therapeutically normal tissue must be protected from undue irradiation.
SPOTTED FEVER
Authors: Pinkerton Henry , Hass George M.
Published: June 2004

Comparative studies were made of the microorganisms present in D. variabilis ticks, some of which served as a control series while the remainder were exposed to infection with D. rickettsi and thereafter maintained under various conditions.

All female ticks contained in their ovaries a coccoid intracellular microorganism.

About 50 per cent of all ticks after refeeding contained rickettsia-like microorganisms in variable numbers in nearly all organs.

The groups of ticks exposed to infection with the virus of spotted fever, in addition to the above mentioned microorganisms, usually harbored large numbers of D. rickettsi, distinguishable with certainty from the non-pathogenic organisms only by their localization in nuclei of tick cells.

No influence upon the size, number, or distribution of either the non-pathogenic rickettsiae or D. rickettsi in ticks was attributable to refeeding, variations of the temperature of incubation, or variations of the length of the period of incubation.

We conclude from the results of these studies that the non-pathogenic rickettsiae which occur in D. variabilis ticks have no well defined relationship to D. rickettsi since they differ from the latter organism not only in the absence of virulence and immunizing properties, but also in their distribution in tick tissues and inability to multiply in the nuclei of cells.
CHEMICAL INVESTIGATIONS ON THE ACTIVE PRINCIPLES OF THE PHENOMENON OF LOCAL SKIN REACTIVITY TO BACTERIAL FILTRATES
Authors: Morell S. A. , Shwartzman Gregory
Published: June 2004

B. coli, meningococcus, and B. typhosus have been cultivated in a diffused broth medium, prepared by immersing cellophane bags containing saline into nutrient broth. An abundant growth occurred inside the bags, while the outside broth remained sterile. Under these conditions, the production of the active principles of the phenomenon of local skin reactivity to bacterial filtrates has been consistent.

When the culture filtrates so obtained were redialyzed against saline, active preparations were obtained which were practically free from non-specific ingredients.
STUDIES ON THE RELATIONSHIP OF THE SEX HORMONES TO INFECTION
Authors: Sprunt Douglas H. , McDearman Sara , Raper James
Published: June 2004

The essential findings of these experiments may be summarized as follows:

The estrogenic hormone after being given for 1 week slows up the spread of India ink but allows it to reach and exceed a normal spread after 24 hours.

After injections of the estrogenic hormone for 3 weeks the spread of India ink is much less than in the control animals.

The resistance of the rabbit to vaccinia is increased if the rabbit has been castrated and then given the estrogenic hormone for a period of 3 weeks before being vaccinated.

At the present time nothing can be said about the action of the gonadotropic hormone on India ink, as the experiments did not agree.
TWO SEROLOGICAL TYPES OF GROUP B HEMOLYTIC STREPTOCOCCI WITH RELATED, BUT NOT IDENTICAL, TYPE-SPECIFIC SUBSTANCES
Authors: Lancefield Rebecca C.
Published: June 2004

1. Among group B hemolytic streptococci one serological type previously described as homogeneous has been shown, instead, to contain two closely related types, distinguishable by reciprocal absorption experiments. These streptococci are designated Types Ia and Ib.

2. Homologous organisms in each case absorb all antibodies from their respective antisera, while organisms of the heterologous related type absorb only the antibody responsible for the cross reactions. Group B streptococci of other types do not absorb the antibodies responsible for the cross reactions between these two related types. The precipitin reaction and passive protection tests in mice were employed in this analysis.

3. The type-specific substance of Type Ia is a polysaccharide. Preliminary study indicates that this is also true of Type Ib. While no data are available concerning the chemical relationships of these substances, it seems probable that the two types elaborate polysaccharides, related chemically as well as serologically.
THE EFFECT OF HYPERTROPHIC CARTILAGE ON BONE MARROW GROWTH
Authors: Huggins Charles , Smith Kenneth McLane
Published: June 2004

Intravenous injections of colloidal thorium dioxide were made in rabbits and moderate amounts caused no significant changes in the cellular elements of venous blood. Thorium dioxide was held locally with great tenacity in the cells of the reticulo-endothelial system in the bone marrow and showed little tendency to migrate despite drastic stimuli to the marrow in the form of anemia and plethora.

In recently injected rabbits, thorium-laden macrophages abutted each cartilage column in the direction of growth where the cartilage was being removed. In marrow which had formed subsequent to injection the macrophages were thorium-free, allowing recognition of the new tissue by x-ray and histological techniques as clear zones. The growth pattern of marrow could be detected in this way.

The bone marrow increases in length principally in the region of hypertrophic cartilage at the metaphyses and it is evident that the increase is facilitated by the presence of macrophages whose primary function is the resolution of the wasted hypertrophic cartilage cells. Growth in thickness of bone marrow occurs at its circumference. In contrast to the zonal growth of bone marrow, growth of the reticuloendothelial system in liver and spleen is chiefly interstitial.
ANAPHYLACTIC SHOCK BY AZODYES. II
Authors: Landsteiner K. , van der Scheer J.
Published: June 2004

From the experiments presented, it follows that the specific precipitation and the production of anaphylactic shock with certain azodyes, as described previously, is due to these substances themselves and is not dependent upon formation of azoproteins by interaction of the dyes with proteins in the test tube or the animal body.

Besides these, some other azodyes which in our tests did not give precipitation with corresponding immune sera were also found, in very small quantities, to induce anaphylactic contraction of the uterus of sensitized guinea pigs.
ANAPHYLAXIS IN THE ISOLATED HEART
Authors: Wilcox Herbert B. , Andrus E. Cowles
Published: June 2004

The isolated hearts of guinea pigs sensitized to horse serum have been shown to react characteristically upon exposure to small amounts of antigen. The cardiac rate is temporarily accelerated and transient alterations in amplitude of contraction are to be observed. Electrocardiographic abnormalities, previously recorded by remote leads during anaphylactic shock in the intact animal, have been recorded by direct leads from the isolated perfused hearts of sensitized animals during this reaction.

An additional effect of anaphylaxis in the isolated heart of the guinea pig is reported: a striking reduction in the rate of flow through the coronary vessels.

The anaphylactic reaction of the isolated heart of the guinea pig has been compared with the action of histamine upon the same preparation and the effect of atropine upon each has been observed. The implications of certain quantitative differences in the influence of atropine upon these reactions are discussed.