bluuebunny/crossref_metadata_2025 huggingface dataset:
A SEDIMENTABLE COMPONENT OF ALLANTOIC FLUID AND ITS RELATIONSHIP TO INFLUENZA VIRUSES
Authors: Knight C. A.
Published: June 2004

Macromolecular material was isolated from normal allantoic fluid by a centrifugation procedure comparable to that currently employed for the concentration and purification of influenza viruses. The yield of material was found to vary with the age of the embryo, reaching a maximum average value after 14 days of incubation at 39°C. of about 0.02 mg. per ml. of allantoic fluid. The purified material was found to contain protein, carbohydrate, and lipid and to have a general composition similar to purified preparations of PR8 influenza virus. A typical preparation of normal material had an isoelectric point at pH 2.3. Sedimentation studies indicated that the normal material can give a variety of sedimentation constants depending upon the concentration and viscosity of the preparations. The sedimentation constant, corrected for viscosity, of the major component of a fresh preparation was 170 S. The diameters of the predominant particles shown in electron micrographs of the normal material and of preparations of PR8 influenza virus were about 40 and 100 mµ, respectively. Serological tests indicated that the normal material is a good antigen and that preparations of both A and B types of influenza virus obtained from allantoic fluids by centrifugation show a strong serological relationship to the normal material. Freezing and thawing of allantoic fluid, and repeated adsorption of virus on red cells, failed to provide a practical basis for the separation of normal protein from the virus entity in the case of PR8 virus. In the cases of similar preparations of F12 and of Lee viruses, a partial separation of a small component was accomplished by fractional centrifugation and this component and the normal protein were shown to be identical or very closely related. Antiserum to the purified normal material inhibited red cell agglutination by A and B types of influenza virus at serum dilutions of 600 to 700, but failed to show significant neutralizing capacity in chick embryo and in mouse tests at a serum dilution of 100. Rabbit antiserum to purified preparations of PR8 virus gave a 50 per cent red cell agglutination inhibition endpoint at a serum dilution of 112,000. Some of the implications of the findings are discussed.
THE EXPERIMENTAL TRANSMISSION OF COLORADO TICK FEVER
Authors: Florio Lloyd , Stewart Mabel O. , Mugrage Edward R.
Published: June 2004

1. The symptoms, history of tick bite, characteristic fever curve, and white blood cell picture should enable the physician to make a diagnosis of Colorado tick fever in nearly every case.

2. The typical white blood cell picture is a depression of the total leucocytes with a shift to the left of the granulocytes. Basophilic cytoplasmic bodies appear occasionally in lymphocytes 3 to 4 days after clinical recovery.

3. The disease can be transmitted serially in human beings by parenteral injection of blood or serum. Such transfers have not resulted in decreased or increased virulence.

4. The naturally acquired and experimental cases of Colorado tick fever are identical in their manifestations.

5. An attack of Colorado tick fever confers a degree of definite immunity to the disease.

6. Colorado tick fever is not a mild form of Rocky Mountain spotted fever since individuals immunized with ground tick vaccine against Rocky Mountain spotted fever are still susceptible to Colorado tick fever.

7. Adult Dermacentor andersoni ticks allowed to feed on typical cases, then carried through to a new generation and fed on susceptible adults, failed to transmit the disease.

8. Colorado tick fever has been successfully transmitted to an experimental animal, the golden hamster.
THE INFLUENCE OF DIET ON THE PRODUCTION OF TUMORS OF THE LIVER BY BUTTER YELLOW
Authors: Opie Eugene L.
Published: June 2004

The presence of fat in the diet accelerates the production of hepatic tumors by p-dimethylaminoazobenzene (butter yellow), and when its quantity is very small, few are produced.

Butter yellow with diets consisting in large part of rice, or with other diets with low protein content, causes nodular cirrhosis, but, rice substituted for sugar in a diet containing protein, fat, and butter yellow with adequate vitamins accelerates the production of tumors though the added rice is insufficient to induce nodular cirrhosis. Rice favors the production of hepatic tumors by agencies that are not yet explained.

Butter yellow produces hepatic tumors in the absence of cirrhosis, but with diets that produce cirrhosis, the frequency of tumors and of their precursors, cystic ducts and cholangiofibrosis, increases with the severity of cirrhosis.
THE COMPARATIVE EFFECTS OF VITAMIN B1 DEFICIENCY AND RESTRICTION OF FOOD INTAKE ON THE RESPONSE OF MICE TO THE LANSING STRAIN OF POLIOMYELITIS VIRUS, AS DETERMINED BY THE PAIRED FEEDING TECHNIQUE
Authors: Foster Claire , Jones James H. , Henle Werner , Dorfman Frieda ,   With the Technical Assistance of Mabel E. Quinby and Dorothy L. Alexander
Published: June 2004

In a paired feeding experiment the effects of vitamin B1 deficiency and of restriction of food intake have been compared. In both groups of animals the number of cases of paralysis and the number of deaths were less than in a control group on an unrestricted amount of the complete diet. The maximum difference occurred on the 15th day after inoculation. The incidence of paralysis and death in the vitamin-deficient group was also less than in the paired restricted group. The maximum difference occurred on the 17th day following inoculation, after which the difference gradually became less. At the end of the experiment (28 days) there was a slightly greater number of deaths in the restricted group than in the vitamin-deficient group. Apparently the effect of vitamin B1 deficiency on the action of the virus of poliomyelitis in the mouse is not due solely to the resulting anorexia.

From the 3rd to the 25th day after inoculation the animals were examined at hourly intervals throughout the day and night. On the 26th and 27th days they were examined every 3 hours. Except for two mice in the unrestricted group dying before the hourly examinations were begun, peripheral paralysis was observed in every animal which died.
PARALLELISM IN THE LETHAL AND HEMOLYTIC ACTIVITY OF THE TOXIN OF CLOSTRIDIUM SEPTICUM
Authors: Bernheimer Alan W.
Published: June 2004

The relation of the lethal toxin to the hemolysin produced by Clostridium septicum, strain 44, has been investigated. The following results suggest that the hemolytic and lethal actions of crude toxin are functions of a single substance or that they are functions of two substances which have similar physical, chemical, and antigenic properties. (1) Within the limits of experimental error, the lethal activity of cultures is directly proportional to their hemolytic activity. (2) Treatment of a culture supernate with hydrogen peroxide diminishes to the same extent its hemolytic and lethal activities. (3) The hemolytic principle and the lethal toxin are adsorbed to approximately the same extent by charcoal. (4) The hemolytic principle and the lethal toxin are adsorbed to approximately the same extent by kaolin. (5) Treatment of culture supernate with erythrocytes results in the removal of most of the lethal activity as well as of most of the hemolytic activity. (6) Both lethal toxin and hemolytic principle are partially destroyed in dilute solution at 36°C. The loss in lethal and hemolytic activities occurs in parallel. (7) The lethal and hemolytic activities of cultures are found to be inseparable by fractional precipitation with ammonium sulfate. (8) The antihemolytic capacity of antitoxic horse serum is found to be directly proportional to the antilethal capacity.
KINETICS OF LYSIS BY CLOSTRIDIUM SEPTICUM HEMOLYSIN
Authors: Bernheimer Alan W.
Published: June 2004

The kinetics of the hemolytic reaction effected by the hemolysin of Clostridium septicum, strain 44, has been studied with regard to the effect of concentration, temperature, and hydrogen ion concentration on the rate of the hemolytic reaction. The kinetics of hemolysis was found to resemble in several respects that of enzyme-catalyzed reactions, but differed in the absence of a clearly defined pH optimum. Attention is drawn to differences between the hemolytic system studied and certain other hemolytic systems.
FURTHER OBSERVATIONS ON THE RELATION OF THE EYE TO IMMUNITY IN EXPERIMENTAL SYPHILIS
Authors: Chesney Alan M. , Woods Alan C.
Published: June 2004

Two experiments are reported in which an attempt was made to determine the extent to which a primary syphilitic infection of the cornea in rabbits is followed by the development of a local corneal immunity, by the generalization of the virus, and by the development of a general immunity to the infection. Female rabbits were inoculated intracorneally with a virulent strain of T. pallidum and the disease was allowed to run its course until the lesions which had developed at the site of inoculation had healed spontaneously. Popliteal lymph nodes were transferred from about one-half of these animals (in the second experiment only) to normal male rabbits and in almost every instance the nodes were proved by this method to contain virulent treponemes, showing that generalization of the syphilitic infection is the rule after intracorneal inoculation. All animals were treated with arsphenamine after the local lesion had subsided (160 and 275 days after the original inoculation). The rabbits were then reinoculated with the homologous strain of treponemes, injections being made into the cornea originally inoculated and also into the skin of the back. In one experiment both corneas were reinoculated.

The incidence of lesions developing in either cornea after reinoculation was higher than the incidence of lesions developing in the skin. The lesions developing in the corneas of the "immune" animals had a longer incubation period and were of shorter duration on the average than the lesions in the control group. As far as intensity of reaction was concerned no difference was observed.

Inoculation of the cornea of rabbits with syphilitic virus is often followed by the development of immunity to the homologous strain of organisms. This immunity is imparted to the skin to a greater extent than to either the cornea inoculated originally or to the opposite uninoculated cornea. It persists after treatment with arsphenamine. It appears to be more marked the longer treatment is postponed.

It is apparent from Table IV that in one-half of all the test animals both cornea and skin were immune to a second inoculation of homologous syphilitic virus. In addition to these there were 5 animals in which the cornea was immune and the skin nearly so, for the lesions which developed in the skin of these animals were minimal in extent and duration and were in no way comparable to those which were observed in the controls. Thus in two-thirds of our animals there developed in both the skin and the cornea, after a primary intracorneal inoculation, a high degree of resistance toward a second inoculation with homologous syphilitic virus, but syphilitic disease of the cornea does not always impart to the cornea itself an absolute immunity to reinoculated homologous virus.
EFFECT OF ENZYME INHIBITORS AND ACTIVATORS ON THE MULTIPLICATION OF TYPHUS RICKETTSIAE
Authors: Greiff Donald , Pinkerton Henry , Moragues Vicente
Published: June 2004

By injection into typhus-infected yolk sacs, a number of agents were tested for possible inhibition or acceleration of rickettsial growth. The previously reported rickettsiostatic activity of penicillin was further confirmed.

Para-aminobenzoic acid, in single injections of 6.6 mg. and 3.3 mg. giving initial concentrations of approximately 1:6000 and 1:12,000 was found to have rickettsiostatic activity approximately equal to that of penicillin. No conclusion could be drawn regarding the possibility of a synergistic action of para-aminobenzoic acid and penicillin. Para-aminobenzoic acid neutralized with sodium hydroxide was found to be as effective as the acid itself, when given in single injections of 6.6 mg. Sodium benzoate, as Well as the ortho and meta forms of aminobenzoic acid were found to be ineffective when given in similar amounts.

Para-aminobenzoic acid, when added to the food in a concentration of 3 per cent, was shown to have a remarkably effective chemotherapeutic action on murine typhus infection in mice.

Sodium fluoride was found at times to accelerate the growth of rickettsiae in the yolk sac, and to cause heavy infection under conditions such that the controls showed practically no multiplication of the organism. When rickettsiostatic substances (penicillin and para-aminobenzoic acid) were combined with sodium fluoride, their rickettsiostatic activity was not demonstrably changed. Other agents studied and found not to affect rickettsial multiplication are listed. The possible mechanisms involved in the observed inhibition and stimulation of rickettsial growth under these conditions are discussed.
IMMUNITY IN MUMPS
Authors: Enders John F. , Cohen Sidney , Kane Lewis W.
Published: June 2004

1. A specific antibody, demonstrable by the technique of complement fixation, regularly appears, or increases in concentration, in the sera of human beings during an attack of mumps or during convalescence.

2. Specific dermal hypersensitivity, demonstrable by the injection of heat-inactivated mumps virus, has been shown to develop in 6 human beings after recovery from mumps.

3. Complement-fixing antibody and the hypersensitive state also emerge as a result of clinically inapparent infection with the virus of mumps.

4. These two phenomena are apparently unrelated in respect to immunologic mechanisms.

5. The data presented indicate that the complement fixation test should prove of value both in diagnosis and in the determination of immunity.

6. The skin test for dermal hypersensitivity, on the other hand, becomes positive after recovery and therefore would appear to be useful only as an index of resistance.
HEREDITY OF THE Rh BLOOD TYPES
Authors: Wiener Alexander S. , Davidsohn I. , Potter E. L.
Published: June 2004

1. The theory of six allelic genes is reviewed, using the new improved nomenclature, and data are summarized regarding the distributions of the eight Rh types among white and negro individuals in New York City.

2. Results are presented of tests for property Hr in a series of 239 white individuals and 49 negroes. Statistical analysis of these data yields results supporting Race and Taylor's hypothesis that anti-Hr sera react with the blood properties determined by the genes Rh2, Rh'' Rho, and rh, but not with the factors determined by genes Rh1 and Rh'.

3. The practical importance of the Hr factor is discussed.
ECK FISTULA LIVER SUBNORMAL IN PRODUCING HEMOGLOBIN AND PLASMA PROTEINS ON DIETS RICH IN LIVER AND IRON
Authors: Whipple G. H. , Robscheit-Robbins F. S. , Hawkins W. B.
Published: June 2004

The Eck fistula shunts the portal blood around the liver which receives its blood only by way of the hepatic artery. There are slight gross and histological changes in the Eck fistula liver of the dog. There is evidence at times of some functional abnormalities of the liver due to the Eck fistula but the dog can tolerate this fistula for 1 to 8 years and appear normal.

Chloroform is tolerated by the Eck fistula dog, which may take twice a lethal dose for the control dog without evidence of significant liver injury. Acacia given by vein is deposited in the Eck fistula liver and impairs further its functional capacity to contribute to hemoglobin production.

The stress of anemia brings out the fact that the anemic Eck fistula animal cannot utilize standard diet factors and iron as efficiently as the anemic non-Eck control dog. The output of new hemoglobin in some instances may drop to one-fourth of normal.

When hypoproteinemia alone or combined with anemia is produced in the Eck fistula dog, we observe at times very low production of plasma protein—seven a drop to one-tenth of normal.

This interrelation of liver abnormality, liver dysfunction, and lessened plasma protein and hemoglobin production is significant. It is generally accepted that the liver is concerned with the production of several plasma proteins—fibrinogen, prothrombin, and albumin.

The experiments above indicate that the liver is concerned directly or indirectly with the production of new hemoglobin. Our belief is that the liver contributes to the fabrication of hemoglobin by means of the mobile plasma proteins which to a large extent derive from the liver.
PASSIVE IMMUNITY TO POLIOMYELITIS IN THE CHIMPANZEE
Authors: Howe Howard A. , Bodian David
Published: June 2004

A series of 6 chimpanzees was inoculated orally with stool from a poliomyelitis patient.

Three of these animals had been given 170 cc. of homologous, hyperimmune monkey serum prior to inoculation, while three were unprotected.

All 6 of the animals were subsequently shown to have poliomyelitis virus in their stools and characteristic lesions in their central nervous systems although none of them developed paralytic poliomyelitis.

All of the immunized animals had demonstrable blood antibody at the time of inoculation although it was present in only one case 30 days later.
NON-PARALYTIC POLIOMYELITIS IN THE CHIMPANZEE
Authors: Bodian David , Howe Howard A.
Published: June 2004

1. Thirteen cases of non-paralytic poliomyelitis infection in chimpanzees are described. Nine of these animals were excreting virus in. their stools at periods of from 3 days to 8 weeks following inoculation.

2. All animals killed during the acute stage showed lesions in the brain distributed in centers usually involved in, and compatible with the presence of, poliomyelitic infection. In 2 chimpanzees typical cord lesions were also present. No lesions were found in the brains of 4 control chimpanzees which had had no virus contact as far as known. The occurrence of a purely systemic or peripheral form of poliomyelitis, without lesions in the central nervous system, has thus not been established.

3. Four instances of arrest of the pathological process near the portal of entry into the brain, indicating partial resistance, are included in this series. One was a chimpanzee inoculated intranasally (A1-75) who had severe tuberculosis at the time of inoculation. The second was an animal convalescent after intracerebral inoculation (A1-74), who sustained a second infection limited to the olfactory bulbs when inoculated intranasally 2 months later with homologous virus. The third (A5-01) was inoculated orally with human stool, but contammation of the olfactory area resulted with infection of the olfactory bulbs and of the forebrain; virus was present in the stools of this animal. The fourth chimpanzee (A48) had suffered an initial non-paralytic attack after stomach tube inoculation, followed by a second attack about 9 months later after oral inoculation with part of the same virus-containing pool (human stools). The second attack consisted of a facial paralysis, with arrest of the pathological process near the facial nucleus.

4. Although cerebral lesions were light in some of the non-paralytic and inapparent infections, their presence in all indicates the action of virus on the central nervous system with the possibihty of production of at least partial local resistance. It is not unreasonable to assume that this may occur in inapparent human cases, although the point is, of course, not susceptible to critical proof in man.

5. The degree of severity of pathological involvement in non-paralytic cases varies from a fully developed distribution of lesions in brain and spinal cord in some chimpanzees, to mild and scattered lesions in the brains of others. This suggests that if the extent of pathological reaction is an indicator of subsequent local resistance to reinfection, the degree of protection afforded by a non-paralytic attack of poliomyelitis to even homologous virus must be variable.
STUDIES ON THE FLEXNER GROUP OF DYSENTERY BACILLI
Authors: Goebel Walther F. , Binkley Francis , Perlman Ely
Published: June 2004

1. Methods for the isolation of the specific antigens of Types V, W, Z, and Newcastle Shigella paradysenteriae are given.

2. The physical, chemical, toxic, and immunological properties of these substances are described.
STUDIES ON THE FLEXNER GROUP OF DYSENTERY BACILLI
Authors: Binkley Francis , Goebel Walther F. , Perlman Ely
Published: June 2004

The chemical and enzymatic dissociation of the specific antigen of Type Z Shigella paradysenteriae has been studied. The chemical, toxic, and serological properties of the products of degradation have been investigated. The nature of the toxic component has been discussed.
CIRRHOSIS OF THE LIVER IN "DONOR" DOGS FED A HIGH FAT DIET AND SUBJECTED TO REPEATED BLEEDINGS
Authors: Holman Russell L.
Published: June 2004

1. In 13 dogs used repeatedly as donors for plasmapheresis and plasma injection experiments and fed a kennel diet that for a period of over a year consisted chiefly of bones with much adherent fat, cirrhosis of the liver occurred in 10. Marked fatty change without definite fibrosis occurred in 2 of the dogs.

2. In control dogs fed the same kennel diet during the same period but not subjected to repeated bleedings, no instance of cirrhosis was observed.

3. In previous plasmapheresis and plasma injection experiments "donor dogs" subjected to similar bleedings over comparable periods but maintained on a different kennel diet did not develop cirrhosis.

4. This series of events suggests that in dogs maintained on a relatively high fat diet repeated bleedings predispose them to cirrhosis of the liver. No data are available to decide the more fundamental question: Do the repeated bleedings remove something (other than hemoglobin) necessary for continued integrity of the liver, or is the cirrhosis the result of relative anoxia or increased lipemia occasioned by the repeated bleedings or perhaps of both combined?
A COMPARISON OF HUMAN AND GUINEA PIG COMPLEMENTS AND THEIR COMPONENT FRACTIONS
Authors: Bier Otto G. , Leyton Graciela , Mayer Manfred M. , Heidelberger Michael
Published: June 2004

1. Defects in methods previously proposed for the estimation of complement components are: failure to ensure an excess of the desired components and failure to ensure absence of anticomplementary effects in the dilution ranges used. Existing data are therefore subject to these uncertainties.

2. Methods are proposed for controlling the adequacy of the reagent for each component, for using it in dilutions below its anticomplementary range, and for reinforcing it with necessary components if these are present in inadequate amounts.

3. Titrations are given of the four components in human and guinea pig complements and in "midpiece," "endpiece," and in the various reagents used, including one with C'3 reactivity, solely, and one withC'4 reactivity.

4. C'3 is shown to be the component which usually limits the titer in guinea pig complement, and C'2 the component of lowest titer in human complement.

5. In immune hemolysis, each component of human complement may be replaced by the corresponding component of guinea pig complement and vice versa.
THE REGENERATIVE CYCLE OF MOTONEURONS, WITH SPECIAL REFERENCE TO PHOSPHATASE ACTIVITY
Authors: Bodian David , Mellors Robert C.
Published: June 2004

1. The regenerative cycle of motoneurons after axon amputation is described, and an attempt made to correlate morphological and chemical events in cell bodies with the growth requirements of regenerating axons.

2. The "normal" pattern of Nissl material in the cell is considered to be the resultant of a steady state in cytoplasmic nucleoprotein. Chromatol is then interpreted as a shift of the balance of nucleoprotein turnover in fa of degradation. The rapid early depletion of Nissl substance in chromatolysis is ascribed to the increased growth requirements created by the active early sprouting of the regenerating axon. Acid phosphatase activity begins to increase above normal levels during this period in the region of nucleopro degradation.

3. The recovery period of chromatolysis due to axon section coincide in time with the phase of gradual lengthening of the regenerating axon, and is thought to represent a gradual restoration of the balance of nucleoprotein degradation and synthesis. During this period acid phosphatase activity is at its height in the region of transformation of Nissl substance, later declines to normal levels when the original pattern of Nissl bodie is restored.

4. The transformation of cytoplasmic nucleoprotein which occurs in chromatolysis after axon section, with the probable liberation (46), and depletion (44), of nucleotides, associated with acid phosphatase activity, suggests the hypothesis that liberated nucleotides or nucleotide compounds may pass down the axon in which they take part in enzymatic activity associated with growth and organization of the newly formed axon. This type of activity would not be incompatible with the ideas previously expressed (30, 81) of a continual function of Nissl substance in maintaining the integrity of the large volume of cytoplasm represented by the axon, as well perhaps as the associated myelin sheath.
CYTOCHROME OXIDASE IN NORMAL AND REGENERATING NEURONS
Authors: Howe Howard A. , Mellors Robert C.
Published: June 2004

Manometric determinations of cytochrome oxidase activity were carried out on grey matter from the thalamus and anterior horn of cats and monkeys under various experimental conditions. The thalamus of the cat was studied following the degeneration of virtually all the thalamic neurons secondary to decortication. In comparing the deneuronated thalamus with the normal one, it was found that approximately 34 per cent of the cytochrome oxidase activity was contributed by the neurons and the balance by neuroglia and mesodermal tissues which on the operated side remained comparable to that of the normal side. Total activity of the normal thalamus averaged 5.52 units per mg. of dry weight where I unit is defined as the amount of cytochrome oxidase required to produce a net oxygen consumption of 10 c.mm. per hour under the specified conditions of the experiment.

The grey matter of the anterior horns of the spinal cord was isolated by a special technique and its cytochrome oxidase activity was compared with anterior horns in which motoneurons had been stimulated to regenerative activity by section of peripheral nerves. Each animal was studied in relation to an anterior horn which was normal and one in which only the functional state of the motoneurons had been changed. Average normal levels of 2.23 units were found for cat anterior horn and 0.69 units for the monkey. Reductions of cytochrome oxidase activity in the range of 22 to 23 per cent were observed for both cat and monkey following nerve section. In the latter the time sequence was carefully studied in relation to the cytological cycle known as chromatolysis and a virus refractory state previously described by us. It was found that maximal reduction of cytochrome oxidase activity coincided with maximal refractoriness of the cells to poliomyelitis virus (30 to 70 days following nerve section). Neither of these states could be correlated in time with maximal chromatolysis (10 to 15 days).
A COMPARISON OF THE EFFECTS OF PYRIDOXINE AND PANTOTHENIC ACID DEFICIENCIES ON THE NERVOUS TISSUES OF SWINE
Authors: Follis Richard H. , Wintrobe Maxwell M.
Published: June 2004

1. When pigs were fed diets deficient in pyridoxine or pantothenic acid, ataxia developed and lesions were found in the sensory neuron.

2. The morphological pattern of the lesions differed in the early stages of the two deficient states. Degeneration of the peripheral process of the sensory neuron was the initial and most prominent feature in pyridoxine deficiency. Chromatolysis was the first evidence of damage to the afferent neuron in pantothenic acid-deficient animals.

3. The possible significance of this evidence of damage to different portions of the sensory neuron is discussed.
THE NEOPLASTIC POTENTIALITIES OF MOUSE EMBRYO TISSUES
Authors: Rous Peyton , Smith William E.
Published: June 2004

A method has been devised whereby the transplanted epidermis of mouse embryos can be selectively exposed to the action of a chemical carcinogen. Scharlach R was dissolved in olive oil with the aim of stimulating and attracting the epidermal cells, methylcholanthrene was added to the solution, and numerous fine globules of it were injected into the thigh muscles of adult mice together with fragments of embryo skin. Much of the oil underwent primary inclusion in the resulting cysts, and the proliferating epidermis, while forming them, extended to not a few of the outlying droplets with result that they too were added to the cyst contents. During these activities the methylcholanthrene came into direct contact with many of the epithelial cells, and later on the layer lining the cyst was continually exposed to the influence of the carcinogen.

The epidermis underwent neoplastic changes with great rapidity; often in less than 4 weeks papillomas and carcinomas had arisen like those deriving from adult epidermis. The growths were punctate in origin and usually multiple. Many were transplanted to adults of the same homologous breed of mice that furnished the embryo material (mice of C strain). The grafts did not uniformly succeed as was the case with those of normal skin of embryos of the same stock,—which regularly grew at first in the new hosts and remained alive long after. The benign papillomas failed to live or barely survived, and the apparently malignant papillomas, though rapidly forming nodules of considerable size, usually regressed later. Some of the carcinomas also regressed or wholly failed, while others gave rise to progressively enlarging tumors. The best results were obtained with grafts in which several neoplasms were intermingled, these flourishing together in the new hosts.

Methylcholanthrene in olive oil exerts an influence on epidermal cells like that of Scharlach R, stimulating them to multiply, attracting them, and causing them to mimic carcinomatous elements.
INCIDENCE AND SPECIFICITY OF THE ANTIBODY FOR A DISTINCTIVE CONSTITUENT OF THE BROWN-PEARCE TUMOR
Authors: MacKenzie Ian , Kidd John G.
Published: June 2004

A detailed study has been made of an antibody which appears in the blood of certain rabbits implanted with the Brown-Pearce carcinoma or injected with extracts of it and which reacts specifically in vitro in mixture with a distinctive sedimentable constituent of the Brown-Pearce tumor cell. The observations as a whole seem to indicate that this constituent of the Brown-Pearce tumor differs notably from certain other sedimentable substances which can be extracted from various rabbit tissues and identified by serological means. The implications of the findings are discussed.
PROTEIN METABOLISM AND PROTEIN RESERVES DURING ACUTE STERILE INFLAMMATION
Authors: Madden S. C. , Clay W. A.
Published: June 2004

Adult dogs were given a proteinless diet plus casein, 80 calories/kilo, 0.4 gm. nitrogen/kilo/day. Sterile controlled inflammation was produced by subcutaneous injection of turpentine. The reaction is characterized by local swelling, induration, and abscess formation, terminated by rupture or incision after 3 to 5 days and by general reactions of malaise, fever, leucocytosis, and increased urinary nitrogen. For 3 to 6 days after turpentine the nitrogen intake was provided in seven experiments by amino acids given parenterally (a solution of the ten essential amino acids (Rose) plus glycine).

A normal dog with a normal protein intake showed a negative nitrogen balance after turpentine—urinary nitrogen doubled even as in inflammation during fasting.

A protein-depleted dog (low protein reserves produced by very low protein intake) given a normal protein intake after turpentine maintained nitrogen balance—urinary nitrogen rose only slightly. With a high (doubled) protein intake the depleted dog showed strongly positive balance.

Normal dogs with high (doubled) protein intakes react to turpentine with doubled urinary nitrogen outputs on individual days and therefore are maintained in approximate nitrogen balance and weight balance. This end may be achieved equally well or better by oral feeding, when such is possible and absorption unimpaired.

The increased nitrogen excretion after injury is again shown directly related to the state of body protein reserves. Increased catabolism not inhibition of anabolism best explains the excess urinary nitrogen. Protection during injury of valuable protein reserves appears possible through an adequate intake of protein nitrogen.
BACTERIOSTATIC EFFECT OF HUMAN SERA ON GROUP A STREPTOCOCCI
Authors: Rothbard Sidney
Published: June 2004

1. Type-specific M extracts and group-specific C carbohydrate of group A streptococci inhibited bacteriostasis of these microorganisms in the presence of normal whole blood and of sera from patients convalescent from streptococcal infections. The inhibition was not specific with respect to streptococcal types and depended merely on the formation of precipitates in the system. The extracts had no antagonistic action in themselves.

2. Preformed precipitates derived from the interaction of an antigen and its homologous antibody or from finely divided coagulated particles of human plasma or ascitic fluid also interfered with the bacteriostasis. The supernatant fluid in which one of these precipitates was formed did not inhibit bacteriostatic activity; therefore, it seems that other possible products of the antigen-antibody reaction were not inhibitory. The relative size of the precipitate particles was a conditioning factor since small particles of one precipitate inhibited bacteriostasis, but large ones of the same precipitate failed to do so.

3. Stained films of blood cells treated with antigen-antibody mixtures which formed a precipitate revealed large cytoplasmic vacuoles containing precipitates in the polymorphonuclear leukocytes and monocytes; such engorged cells subsequently failed to phagocytize streptococci in homologous serum. Blood cells treated in the same manner, except that the antigen-antibody mixtures formed no precipitate, contained no vacuoles, and these cells were able to phagocytize the streptococci.

4. Leukocytes studied in the living state in the presence of colored precipitate and streptococci sensitized by convalescent human serum showed unselective phagocytosis of both precipitate and bacteria. The capacity of these leukocytes to ingest material however was limited.

5. As a result of non-selective saturation of their phagocytic capacity in the bacteriostatic systems containing both streptococci and precipitate, the limited number of leukocytes phagocytized only a fraction of the streptococci; consequently the remainder were able to multiply.
THE CHEMICAL ALTERATION OF A BACTERIAL SURFACE, WITH SPECIAL REFERENCE TO THE AGGLUTINATION OF B. PROTEUS OX-19
Authors: Cohen Seymour S.
Published: June 2004

The chemical substitution of a bacterial surface has been effected by the addition of benzene sulfonyl chloride to B. proteus OX-19. The substitution of imidazole and amino groups on the bacteria has been followed by the microelectrophoretic method. Concomitant changes in the agglutinability of substituted organisms have been observed, without appreciable change in the antibody-combining capacities of the organisms. The significance of these observations has been discussed.
INVESTIGATIONS ON THE OCCURRENCE OF Rh SUBSTANCES IN AMNIOTIC FLUID
Authors: Witebsky Ernest , Mohn James F. ,   With the Technical Assistance of Lucille F. Collins and Doris J. Howles
Published: June 2004

1. Rh substances are found in amniotic fluid. Not all anti-Rh sera seem to be suitable for the detection of Rh substances in amniotic fluid. Careful selection of Rh antisera, as well as quantitative considerations, determine success or failure of their demonstration.

2. The baby's Rh type and not the mother's determines the occurrence of Rh substances in amniotic fluid.

3. There are Rh secretors and Rh non-secretors. At least four out of five individuals are secretors.

4. The secretion of Rh substance into the amniotic fluid would seem to be entirely independent of the secretion of the blood group specific substances.

5. The majority of Rh-positive amniotic fluids seem to contain both Rh1 and Rh2 substances. However, in certain instances fluids belonging to the pure Rh1 type or pure Rh2 type were found.

6. Three cases of erythroblastosis were described. All three came from Rh-negative mothers with Rh-positive babies. The amniotic fluids of all three failed to reveal the presence of Rh substances.
PLASMA PROTEIN PRODUCTION INFLUENCED BY AMINO ACID MIXTURES AND LACK OF ESSENTIAL AMINO ACIDS
Authors: Madden S. C. , Anderson F. W. , Donovan J. C. , Whipple G. H.
Published: June 2004

When blood plasma proteins are depleted by bleeding with return of red cells suspended in saline (plasmapheresis) it is possible to bring dogs to a steady state of hypoproteinemia and a constant level of plasma protein production if the diet nitrogen intake is controlled and limited. Such dogs are outwardly normal but have a lowered resistance to infection and intoxication and probably to vitamin deficiency.

When the diet nitrogen is provided by certain mixtures of the ten growth essential amino acids plus glycine, given intravenously at a rapid rate, plasma protein production is good. The same mixture absorbed subcutaneously at a slower rate may be slightly better utilized. Fed orally the same mixture is better utilized and associated with a lower urinary nitrogen excretion.

An ample amino acid mixture for the daily intake of a 10 kilo dog may contain in grams dl-threonine 1.4, dl-valine 3, dl-leucine 3, dl-isoleucine 2, l(+)-lysine·HCl·H2O 2.2, dl-tryptophane 0.3, dl-phenylalanine 2, dl-methionine 1.2, l(+)-histidine·HCl·H2O 1, l(+)-arginine·HCl 1, and glycine 2. Half this quantity is inadequate and not improved by addition of a mixture of alanine, serine, norleucine, proline, hydroxyproline, and tyrosine totalling 1.4 gm.

Aspartic acid appears to induce vomiting when added to a mixture of amino acids. The same response has been reported for glutamic acid (8).

Omission from the intake of leucine or of leucine and isoleucine results in negative nitrogen balance and rapid weight loss but plasma protein production may be temporarily maintained. It is possible that leucine may be captured from red blood cell destruction.

Tryptophane deficiency causes an abrupt decline in plasma protein production. No decline occurred during 2 weeks of histidine deficiency but the urinary nitrogen increased to negative balance.

Plasma protein production may be impaired during conditions of dietary deficiency not related to the protein or amino acid intake. Skin lesions and liver function impairment are described. Unidentified factors present in liver and yeast appear to be involved.
PLASMA PROTEIN PRODUCTION AS INFLUENCED BY PARENTERAL PROTEIN DIGESTS, VERY HIGH PROTEIN FEEDING, AND RED BLOOD CELL CATABOLISM
Authors: Madden S. C. , Kattus A. A. , Carter J. R. , Miller L. L. , Whipple G. H.
Published: June 2004

When blood plasma proteins are depleted by bleeding, with return of the washed red cells (plasmapheresis), it is possible to bring dogs to a steady state of hypoproteinemia and a constant level of plasma protein production if the diet nitrogen is controlled and limited. Such dogs are outwardly normal but have a lowered resistance to infection and to certain intoxications.

Certain protein digests given by vein may favor good production of plasma protein, as well as nitrogen and weight equilibrium, over long periods in these standardized dogs. These digests may be equally effective when given subcutaneously or intraperitoneally and more effective orally (one dog). Certain other digests may not be well utilized.

The total nitrogen of the protein digests is better retained upon oral feeding than parenteral injection. Most of the excess nitrogen excretion is not in the urea and ammonia fraction of the urine.

The rate of plasma protein production may reach as high as 1 gm./kilo/day in the dog when ample protein of good quality is fed.

The products of catabolism of red blood cells in vivo may add to the production of plasma protein, at least during the administration of casein digest by vein.
IMMUNOCHEMICAL STUDIES ON BLOOD GROUPS
Authors: Kabat Elvin A. , Bezer Ada E.
Published: June 2004

1. With purified blood group A and B specific substances from the gastric mucin of pigs precipitin reactions can be obtained in sera containing homologous isoagglutinins. By microquantitative precipitin technics the anti-A and anti-B content of normal and immune isoagglutinin-containing sera can be estimated on a weight basis.

2. There was a general correlation between antibody N precipitable from the sera of groups O and B by A substance and the agglutinin titer for A erythrocytes before and after immunization with blood group substances.

3. The reaction between A substance and its homologous isoagglutinin present in the sera of immunized individuals was of the same type as in other antigen-antibody systems.
MEASUREMENT OF ANAEROBIC GLYCOLYSIS IN BRAIN AS RELATED TO POLIOMYELITIS
Authors: Utter M. F. , Reiner John M. , Wood Harland G.
Published: June 2004

Experiments with mouse brain, homogenates show that the anaerobic glycolysis of such preparations can be increased tenfold by addition of appropriate coenzymes and phosphate esters. The previously reported alterations in anaerobic glycolysis during poliomyelitis, as measured with low activity preparations, are believed to be of doubtful value in so far as the changes may be related to any specific phase of metabolism. In order to obtain this type of information, the experiment usually must be designed specifically to measure the desired factor.
HEREDITARY ACHONDROPLASIA IN THE RABBIT
Authors: Pearce Louise , Brown Wade H.
Published: June 2004

Hereditary achondroplasia (chondrodystrophia foetalis) in the rabbit has been described in the present and preceding papers (1, 2). It is the first instance of this abnormality in rodents to be reported. The variation arose in pure bred Havana stock.

The abnormality is determined by the expression of a simple recessive unit factor, affected individuals being homozygous for the factor. Females are somewhat more frequently affected than males, but the character is not sex-linked. Rabbits heterozygous for the factor as determined by appropriate breeding tests have a perfectly normal appearance at birth and in later life. The condition appears to be determined solely by the genetic constitution of the animal. Attention was drawn to the fact that although the development of the achondroplastic form proceeds to birth at term, death regularly occurs at the time of or very shortly after parturition. This feature of the condition is briefly discussed.
MAXIMAL HEMOGLOBIN AND PLASMA PROTEIN PRODUCTION UNDER THE STIMULUS OF DEPLETION
Authors: Robscheit-Robbins F. S. , Miller L. L. , Whipple G. H.
Published: June 2004

The maximal output ceiling for hemoglobin in anemia due to blood loss is about 60 gm. per week—the dog receiving a rich protein diet plus high iron intake. Ferrous and ferric salts are equally effective. Iron intravenously plus a rich protein diet may push this level up to 90 to 100 gm. per week. Evidently iron absorption is a limiting factor.

Maximal output for hemoglobin plus plasma protein in doubly depleted dogs may reach 120 to 130 gm. per week and using intravenous iron may reach 140 to 160 gm. per week.

Maximal output for plasma protein alone in hypoproteinemia due to plasmapheresis reaches 60 to 70 gm. per week but this is not the true ceiling. Technically we cannot remove the new plasma protein as fast as it is formed and the hypoproteinemia is not maintained in the face of a rich protein diet intake. Furthermore the evidence points to the protein circulating pool contributing to the accretion of tissue protein in such dogs with a strong positive nitrogen balance and weight gain.

Maximal figures for hemoglobin production in anemia run close to 1 gm. hemoglobin per kilo per day. Maximal figures for new hemoglobin plus plasma protein production in anemia and hypoproteinemia using iron given intravenously, may reach 1.5 gm. blood protein per kilo per day. The actual maximal plasma protein production equals about 1 gm. per kilo per day but the true production ceiling cannot be reached by this technique, for reasons given above.
MECHANISM OF THE AUGMENTING ACTION OF MINERAL OIL ON ANTIBODY PRODUCTION
Authors: Ehrich W. E. , Halbert S. P. , Mertens E. , Mudd S.
Published: June 2004

A comparative study was made in rabbits of antibody production and tissue changes following the injection into the foot pads, of saline in Falba and mineral oil emulsion, of killed cells of Shigella paradysenteriae Flexner in saline, and of killed cells of Shigella paradysenteriae in saline in Falba-mineral oil emulsion.

It was found that antibody production was greatly prolonged by the emulsification in oil. While with antigen in saline the serum titers began to fall 9 days after injection and disappeared somewhere between the 3rd and 6th months, with antigen in paraffin oil they began to drop only after 14 days, and were still high after 10 months, when the experiment was ended.

The toxic effects of the antigen were greatly reduced by the emulsification in oil. A subcutaneous dose of 1.5 mg. of antigen in saline caused mesenchymal reactions in lung, liver, and spleen as well as toxic degeneration and sometimes necrosis of the liver whereas eight times as much of the antigen in oil produced no systemic lesions.

Oil drops remained detectable in the foot pad until the end of the experiment. Bacteria remained visible in the oil for 1 week or more, but with saline they disappeared within 1 day. The latter observation shows that retention of antigen at the site of injection is at least one of the mechanisms of prolongation of antibody formation by paraffin oil.

The tissue reaction in the foot pad to antigen in oil was largely one of suppuration with the production of persisting mononuclear granulomata whereas after antigen in saline it was chiefly one of catarrhal inflammation, subsiding within a month. The changes in the regional lymph nodes were essentially those of lymphatic hyperplasia with the production of numerous lymphocytes and large active secondary nodules, the macrophages remaining subsidiary. The lymphocytic reaction in the lymph nodes closely paralleled the antibody response but the monocytic reaction at the site of injection was not correlated with this response; in fact, in the antigen in oil experiments the monocytic reaction reached its height after the peak of antibody production.

The tissue changes observed in the various experiments were consistent with the finding previously reported from this laboratory, that the lymphocyte is concerned in antibody formation.
PREVENTION OF PNEUMOCOCCAL PNEUMONIA BY IMMUNIZATION WITH SPECIFIC CAPSULAR POLYSACCHARIDES
Authors: MacLeod Colin M. , Hodges Richard G. , Heidelberger Michael , Bernhard William G.
Published: June 2004

1. Immunization of man with 0.03 to 0.06 mg. of each of the capsular polysaccharides of pneumococcus types I, II, V, and VII, given in a single subcutaneous injection, has been shown to be effective in preventing pneumonia caused by these types but not that due to heterologous types.

2. Immunity appears within a period of 2 weeks following injection of the polysaccharides. Its duration was not determined, although 6 months can be set as a minimum.

3. Immunization of alternate subjects in the population reduced greatly the incidence of pneumonia in the non-immunized.

4. The carrier rate for pneumococcus types I, II, V, and VII was lowered significantly in the immunized group as compared with the controls. It is suggested that an over-all reduction in the incidence of carriers was responsible for the lowered rates for pneumococcal pneumonia in the non-immunized group.