bluuebunny/crossref_metadata_2025 huggingface dataset:
CELL STATE AS AFFECTING SUSCEPTIBILITY TO A VIRUS
Authors: Friedewald William F.
Published: June 2004

Rabbit skin can be rendered abnormally susceptible to papilloma virus infection by preliminary treatments with a variety of agents. The most effective agents thus far found are 0.3 per cent methylcholanthrene in benzene and a mixture in equal parts of turpentine and acetone, applied four or five times at 2 day intervals. When virus is inoculated into skin altered by these agents, either intradermally or by inunction after scarification, papillomas appear earlier and in greater number than on normal skin, and much higher dilutions give rise to growths. The method provides a means of detecting amounts of virus which cause no papillomas upon inoculation into normal skin.

Papilloma virus material which is rubbed into scarified normal or hyperplastic skin is largely lost in the scabbing which ensues, and nearly all of it fails to reach susceptible cells. The preparatory agents which increase the effectiveness of the virus bring about marked epidermal hyperplasia, and the hyperplastic tissue regenerates with greater rapidity when scarified. The agents evidently act in large part by providing young epidermal cells in quantity to the virus, as also by inducing a richer vascularization than ordinary in support of the papillomatous proliferation. It is possible that they also act by providing especially susceptible cells. The implications of the findings are discussed.
RED CELL AND PLASMA VOLUMES (CIRCULATING AND TOTAL) AS DETERMINED BY RADIO IRON AND BY DYE
Authors: Hahn P. F. , Ross J. F. , Bale W. F. , Balfour W. M. , Whipple G. H.
Published: June 2004

1. Application of the principles of hydrodynamics to the problem of blood flow and blood volume indicates that the calculation of blood volume and cell volume from the venous hematocrit and plasma volume (as determined by the dye method) is subject to considerable error.

2. This conclusion is borne out by determinations of total cell volume by viviperfusion and with the use of radioactive iron tagged erythrocytes, which have shown the erythrocyte volume to be only 70 to 75 per cent of the volume indicated by the previously mentioned calculations.

3. The average hematocrit of the entire vascular system is considerably lower than the hematocrit of the large vessels, and the cell-plasma ratio of the smaller vessels is still less.

4. In the dog there are no considerable stores of immobilized erythrocytes, and the total erythrocyte volume and circulating erythrocyte volume are identical.

5. The "rapidly circulating blood volume" can be determined by dividing the erythrocyte volume by the venous hematocrit, and is found to be considerably less than the total blood volume.

6. The concept of the "rapidly circulating plasma volume" is introduced, and it is found to be approximately 80 per cent of the total plasma volume.

7. The volume of plasma in the peripheral, cell free, sluggishly moving plasma films, plus that contained in small vessels in which no red cells are present, is also determined and found to be approximately 20 per cent of the entire plasma volume.

8. The existence and magnitude of these fractions of the blood plasma volume should receive consideration in studies of blood flow and blood volume.
THE REACTION OF PERIPHERAL BLOOD VESSELS TO ANGIOTONIN, RENIN, AND OTHER PRESSOR AGENTS
Authors: Abell Richard G. , Page Irvine H.
Published: June 2004

1. Both renin and angiotonin in small doses cause constriction of the arterioles in the ears of normal rabbits, as seen directly with the microscope. Capillaries appear unaffected while venules exhibit slight or no constriction with small doses and moderate constriction with large doses. The flow of blood through the tissues is not reduced except when very large doses are administered. Tyramine and methylguanidine sulfate in isopressor amounts act somewhat similarly.

2. Isopressor amounts of epinephrine and pitressin, by contrast, elicit severe vasoconstriction of arterioles lasting longer than that due to angiotonin, and flow of blood is sharply reduced or abolished altogether. The degree of venular constriction was also greater, while the capillaries remained unaffected.

3. The vasoconstrictor action of angiotonin on peripheral vessels in moat chambers in normal rabbit's ears is indistinguishable from that of renin, except that it is more rapid.
HUMAN ALLERGY TO MAMMALIAN SERA
Authors: Simon Frank A.
Published: June 2004

Four patients allergic to many mammalian sera were found to have circulating, skin-sensitizing antibodies for these sera. A study of these antibodies by in vitro neutralization and subsequent local passive transfer showed that, in the case of each patient, one particular mammalian serum neutralized antibodies for all sera whereas other mammalian sera neutralized antibodies for themselves alone or for themselves plus one or several additional sera but not for all sera. The possibility of multiple common allergenic determinants in mammalian sera is discussed.
SEROLOGICALLY REACTIVE POLYSACCHARIDES PRODUCED THROUGH THE ACTION OF BACTERIAL ENZYMES
Authors: Hehre Edward J. , Sugg John Y.
Published: June 2004

A serologically reactive polysaccharide of dextran nature was produced from sucrose by the action of some enzyme or similar heat-labile agent contained in sterile filtered extracts derived from sucrose broth cultures of Leuconostoc mesenteroides. Rigorous controls were included to prove that this reaction occurred in the absence of microorganisms.

Purified preparations of the dextran formed by the sterile extracts were similar to the dextran elaborated in sucrose broth cultures of the bacteria in respect to both chemical and serological properties. The serological likeness was established not only by tests against leuconostoc antiserums but also by cross reactions with antiserums of Types 2, 20, and 12 pneumococci and by tests against a series of variously absorbed antiserums.
STUDIES ON MENINGOCOCCAL INFECTION
Authors: Menzel A. E. O. , Rake Geoffrey
Published: June 2004

From meningococcus Type II broth autolysates, a substance, corresponding to the protective antibody has been isolated. This substance, termed kappa substance, is firmly connected with protein but can be separated by the action of proteolytic enzymes. Methods of preparation and purification are given, together with chemical and serological data. In whole cells from young cultures, this substance is also connected with protein, especially with one protein fraction which requires highest alkali concentration to effect solution.
STUDIES ON HYPOALBUMINEMIA PRODUCED BY PROTEIN-DEFICIENT DIETS
Authors: Elman Robert , Brown Frank A. , Wolf Harriet
Published: June 2004

Serum albumin depletion, induced by a 3 weeks fast, was completely corrected within 1 week by the ingestion of a diet consisting solely of meat administered ad libitum. The average protein intake was 50 gm. per kilo of body weight per day. A 2nd week of the same diet produced no further increase in serum albumin though it did lead to an increase in the globulin fraction.
RED CELL AND PLASMA RADIOACTIVE COPPER IN NORMAL AND ANEMIC DOGS
Authors: Yoshikawa H. , Hahn P. F. , Bale W. F.
Published: June 2004

Following ingestion of radioactive copper by the dog, the metal appears quickly in the plasma, the concentration reaching its peak in from 2 to 5 hours, after which it falls abruptly. Demonstrable amounts are still present after 2 days. The radioactive copper likewise appears rapidly in the circulating red blood cells, and there is a slow but gradual increase in its concentration over a 2 day period.

It is suggested by the data that in the animals in which hematopoietic activity is accelerated the uptake of radio-copper is somewhat more extensive. The possibility that this is due to greater adsorption by the new red cells in these instances is not ruled out.
ARTERIAL HYPERTENSION IN RATS
Authors: Schroeder Henry A. , Neumann Charles
Published: June 2004

1. When rats developed cardiac hypertrophy or elevation of blood pressure as a result of one of several methods designed to bring about arterial hypertension, renal vascular disease occurred frequently.

2. When injury to one kidney was followed by cardiac hypertrophy or elevation of blood pressure, vascular lesions were found with considerable regularity in the opposite one, as well as in the one injured.

3. Renal lesions rarely occurred in the absence of cardiac hypertrophy or elevated blood pressure.

4. Renal vascular lesions in rats are occasioned, therefore, by injury to one kidney and are usually associated with, and dependent on, the presence of arterial hypertension.
TOXEMIA OF PREGNANCY IN THE GUINEA PIG
Authors: Foley Edward J.
Published: June 2004

The clinical and pathological manifestations of a disease occurring in the late stages of pregnancy or following parturition in the guinea pig are described. The similarity of this disease to toxemia of pregnancy in the rabbit is discussed. The disease appears to be of endogenous origin and is in some way associated with a disordered metabolism occurring at about the time of parturition.
THE HYPOPHYSIS AND SECRETION OF INSULIN
Authors: Houssay B. A. , Foglia V. G. , Smyth F. S. , Rietti C. T. , Houssay A. B.
Published: June 2004

The ability of the pancreas, from various types of dogs, to correct diabetic hyperglycemia has been studied (Table XI). The pancreas from one animal was united by a vascular union with the neck blood vessels of another dog which had been pancreatectomized for 20 hours. The time necessary to reduce the blood sugar level to 120 mg. per cent was determined.

1. Pancreas from 6 hypophysectomized dogs produced a normal insulin secretion, showing that an anterior pituitary hormone is not necessary for its production or maintenance.

2. In 14 of 17 normal dogs given anterior pituitary extract for 3 or more consecutive days and presenting diabetes (fasting blood sugar 150 mg. per cent or more) the pancreas showed diminished insulin production.

3. In animals which remained diabetic after discontinuing the injections of hypophyseal extract, the pancreas islands were markedly pathologic and the insulin secretion was practically nil.

4. When hyperglycemia existed on the 2nd to 5th day but fell later, the insulin secretion of 5 dogs was normal in 2, supernormal in 1, and less than normal in 2. Histologic examination showed a restoration of beta cells.

5. In 14 dogs resistant to the diabetogenic action of anterior pituitary extract, as shown by little or no change in blood sugar, the pancreatic secretion of insulin was normal in 6 cases, supernormal in 3, and subnormal in 5 cases. Clear signs of hyperfunction of B cells were observed. In 6 resistant animals a high blood sugar (150 mg. per cent) appeared shortly before transplanting, but insulin secretion was normal in 4, supernormal in 1, and subnormal in 1 case.

6. With one injection of extract and 1 day of hyperglycemia the capacity of the pancreas to secrete insulin was not altered.

7. A high blood sugar level lasting 4 days does not alter the islets. The hypophyseal extract acts, therefore, by some other mechanism. In normal dogs, the continuous intravenous infusion of glucose for 4 days maintained the blood sugar at levels as high as those after pituitary extract. In these animals the B cells were hyperplastic and insulin secretion normal.

8. Anterior hypophyseal hyperglycemia is due at first to extrapancreatic factors which are the most important, and last only during the injections of extracts. Pancreatic factors appear afterwards and are responsible for permanent diabetes.

Hypophyseal extract produces histological changes in many tissues and damages the Langerhans islands. The coexistent high blood sugar probably exhausts the B cells and exaggerates their injury.

9. In all cases there is a relation between the cytology of the islet B cells and the insulin secreting capacity.
THE EFFECT OF EXTERNAL TEMPERATURE ON THE COURSE OF INFECTIOUS MYXOMATOSIS OF RABBITS
Authors: Parker R. F. , Thompson R. L.
Published: June 2004

Rabbits, convalescent from vaccinia and in good general health, were subjected to infection with myxoma during a period of exposure to a high external temperature. It was observed that in proportion as the temperature was elevated, a profound change in the course of the myxoma infection occurred. At the highest temperatures, the disease was held completely in abeyance, and no lesions appeared within 17 days of observation. At lower temperatures, lesions appeared which tended to be circumscribed, and which reached their maximum development within 6 or 8 days after inoculation. Regression then set in and complete healing occurred. There was wide variation in the degree of protection which a given temperature conferred on an individual rabbit as measured by the amount of virus required to cause infection, although for single animals the difference in concentration of virus required to produce consistently positive and consistently negative results was not apparently different from that obtaining in the controls. With the data at hand, it does not appear justifiable to draw final conclusions as to the state of immunity of the animals which survived the modified infection.
MORPHOLOGICAL STRUCTURE OF THE VIRUS OF VACCINIA
Authors: Green R. H. , Anderson T. F. , Smadel J. E.
Published: June 2004

The pictorial data obtained by means of the electron microscope indicate a remarkable regularity in the morphology of the elementary body of vaccinia. The virus particles apparently have internal structure and some sort of limiting membrane.
CONSTITUENTS OF ELEMENTARY BODIES OF VACCINIA
Authors: Hoagland Charles L. , Ward S. M. , Smadel Joseph E. , Rivers Thomas M.
Published: June 2004

Purified elementary bodies of vaccinia have been tested with a variety of substrates and found to possess phosphatase, catalase, and lipase activity. Tests for malate, succinate, pyruvate, and lactate dehydrogenases were negative.

Interpretation of these results is complicated by the observation that elementary bodies of vaccinia adsorb relatively large quantities of certain enzymes from dilute solutions. These enzymes are not eluted by procedures of washing and centrifuging similar to those carried out in the preparation of the virus. For this reason, the presence of phosphatase, catalase, and lipase in the purified virus may well be accounted for on the basis of adsorption from the host tissues which are known to be rich in these particular enzymes. That some degree of specificity in this adsorption is to be recognized is shown by the failure of the virus to adsorb urease, an enzyme of vegetable origin.

Until some method can be devised which will distinguish between the enzymes of the host cell and those which may be integral parts of the virus it would seem that the problem of the enzyme constituents of vaccine virus is incapable of definite solution.
THE REACTION BETWEEN THE ENZYME TYROSINASE AND ITS SPECIFIC ANTIBODY
Authors: Adams Mark H.
Published: June 2004

1. Antibodies to the enzyme tyrosinase, obtained from the mushroom Psalliota campestris, have been produced in rabbits and human beings.

2. These antibody preparations, though precipitating the enzyme from solution, do not affect its catalytic activity.
ADSORPTION OF INFLUENZA HEMAGGLUTININS AND VIRUS BY RED BLOOD CELLS
Authors: Hirst G. K.
Published: June 2004

A number of experiments were performed on the adsorption of influenza hemagglutinins on chicken red blood cells, from which the following conclusions were drawn:—

1. When chicken red blood cells and preparations of influenza viruses were mixed together, the influenza hemagglutinins present were rapidly adsorbed onto the cells. After varying lengths of time, dependent on the conditions of the experiment, the adsorbed hemagglutinins began to elute from the cells. With the Lee strain at 23°C. and the PR8 strain at 37°C. almost all of the adsorbed agglutinin was released in 4 to 6 hours.

2. When the number of red cells used for adsorption was increased, the speed and degree of adsorption of the hemagglutinins increased. The time of maximum adsorption of hemagglutinins was the same, regardiess of red cell concentration, and with the larger amounts of red cells the speed and degree of elution was decreased.

3. When adsorption of PR8 virus agglutinins was carried out at 4°C. the adsorption was rapid and nearly complete. When the reaction was carried out at higher temperatures (27° and 37°C.), the adsorption was equally rapid but was progressively less complete with rise in temperature. At 4°C. the maximum adsorption was not reached for 5 hours; at 27°C. it was reached in 25 minutes; and at 37°C. the greatest degree of adsorption was attained between 3 and 5 minutes. The amount of elution observed at 4°C. at 18 hours was negligible, but the degree of elution increased with temperature so that at 37°C. almost all of the adsorbed agglutinin was released in 6 hours' time.

4. Red cells which had adsorbed and then fully eluted the agglutinin were not capable of adsorbing a detectable amount of fresh agglutinin. In addition, such cells would no longer agglutinate even though exposed to fresh virus suspensions.

5. The hemagglutinin of influenza B virus was capable of being adsorbed on and eluted from several successive lots of chicken red cells without appreciable loss of agglutinating activity.

6. The hemagglutinins of the PR8 and Lee strains were rapidly inactivated at 60°C. The presence of active virus was not necessary for the occurrence of the adsorption-elution reaction on chicken red cells.

7. The activity of the portion of the red cells responsible for the adsorption of the hemagglutinins persisted, though in reduced amount, even after heating for 5 minutes at 100°C. Hemagglutinins were adsorbed and eluted from red cell stroma.

8. The infective agent in influenza virus suspensions was adsorbed by chicken red cells simultaneously with the adsorption of hemagglutinins. 95 per cent of the infective agent was removed from suspension by the red cells after contact for 15 minutes. From then on the infective agent was gradually released from the red cells. After 4 hours the 50 per cent mortality titer of the supernatant fluid was as high as at the beginning of the experiment.
THE CONTROL OF THE RENAL EXCRETION OF WATER
Authors: Shannon James A.
Published: June 2004

1. The administration of the posterior pituitary antidiuretic hormone by constant intravenous infusion has been used to examine the two characteristic actions of the hormone; namely, the facilitation of the active renal tubular reabsorption of water distally in the nephron and the inhibition of the renal tubular reabsorption of sodium proximally.

2. Experimental evidence was obtained which indicates that variations in the excretion of water and electrolyte involve the integration of these two actions with obscure variables which are discemible in the experimental data but are not subject to definition at this time.

3. Graded antidiuresis in the animal with diabetes insipidus, when normally hydrated, was only obtained in the range of 0.001 to 0.005 unit (pressor) per hour. This range of hormone administration was also found to be physiologically active in the normal animals. These observations together with others permit the placing of the normal rate of liberation of the antidiuretic hormone in a10 to 15 kilo dog in the range of 0.001 to 0.005 unit per hour.
QUANTITATIVE STUDIES OF THE PHOTOCHEMICAL DESPECIATION OF HORSE SERUM
Authors: Henry J. P.
Published: June 2004

1. Normal horse serum was irradiated for periods of 3 to 4 days, with visible light or with ultraviolet light of known intensity and wave length. The photosensitizer hematoporphyrin was employed in some instances. The serum was exposed to the air in thin layers, and thoroughly agitated throughout irradiation.

2. The irradiated sera were unchanged in color, and over 90 per cent of the original protein content remained precipitable by phosphotungstic acid.

3. Studies of the antigenicity of the sera were carried out on guinea pigs and rabbits. Fresh antigenicities of deviated specificity and of an activity of the order of 1/50th, 1/1,000th, and less than 1/20,000th that of normal horse serum were obtained. The residual content of material having the same antigenic specificity as normal horse serum was estimated as approximately equivalent in activity to dilutions of normal horse serum of 1 cc., 1/10 cc., and less than 1/100 cc. per litre respectively.
THE IMMUNIZATION OF FOWLS AGAINST MOSQUITO-BORNE PLASMODIUM GALLINACEUM BY INJECTIONS OF SERUM AND OF INACTIVATED HOMOLOGOUS SPOROZOITES
Authors: Russell Paul F. , Mohan B. N.
Published: June 2004

This paper reports attempts to immunize domestic fowls against mosquito-borne infections of Plasmodium gallinaceum by means of (a) vaccination with inactivated homologous sporozoites; (b) injections of sera, both normal sheep serum, and serum from fowls chronically infected with the homologous Plasmodium, (c) combinations of both sporozoite vaccine and serum.

It was possible to reduce the normal malaria death rate (55.4 per cent) in these fowls by each of the above methods but most markedly by the combined prophylactic treatment. Mortality rates were 21.1 per cent in vaccinated fowls, 16.7 per cent in serum-treated fowls, and 7.3 in those having the combined treatment.

Intensity of infection was measured by counting the percentage of red cells infected each day. It was found that in each group of fowls having prophylactic treatment the average of highest percentages of red cells infected was less than in untreated malarious fowls (30.1 per cent). The average figure was 20.5 per cent in vaccinated fowls, 17.9 per cent in those having serum injections, and 15.0 per cent in those having combined treatment.

The prepatent period was not markedly affected by any of the prophylactic procedures. It averaged 9.1 days in the untreated group, 8.9 days in both the vaccinated and serum-treated groups, and 9.7 days in the group having combined treatment.

The results seemed to demonstrate an interaction of both cellular and humoral agencies in defence against malaria, since the greatest immunizing effect was seen in the series having both sporozoite vaccine and serum injections.
LOW PROTEIN DIET AUGMENTS HYPERPROTEINEMIA PRODUCED BY REPEATED INJECTIONS OF HOMOLOGOUS PLASMA
Authors: Holman Russell L.
Published: June 2004

1. In 4 dogs maintained on a high protein diet (lean meat) repeated intravenous injections of plasma obtained from healthy donor dogs (18 to 24 injections during the course of 3 to 4 weeks, totalling 1595 to 4355 cc.—averaging 1800 cc. when figured on thc basis of a 5 kg. dog) resulted in a mean increase in the plasma protein concentration of 20 per cent (from 7.1 per cent to 8.5 per cent).

2. In 7 dogs maintained on a low protein diet (only 7 per cent of total caloric value derived from protein) almost identical injections of donor's plasma caused an average increase in the plasma protein concentration of 40 per cent (from 6.7 per cent to 9.4 per cent).

3. The albumin:globulin ratio in the group on the low protein diet showed an average fall of 30 per cent (from 1.4 to 0.9) while in the group on the high protein diet the change in this ratio was insignificant (from 1.3 to 1.2).

4. In all dogs in both groups there was a consistent fall in the hematocrit value of about 15 to 20 per cent (from 49 to 40, or 18 per cent) which can be explained in part at least by the increase in plasma volume of about 15 per cent.

5. There were no significant changes in body weight or in plasma N.P.N.
THE VIRUS OF INFECTIOUS FELINE AGRANULOCYTOSIS
Authors: Syverton J. T. , Lawrence J. S. , Ackart R. J. , Adams W. S. , Ervin D. M. , Haskins A. L. , Saunders R. H. , Stringfellow M. B. , Wetrich R. M.
Published: June 2004

Thirty-two strains of an infectious filterable agent, with properties that establish it as a virus, have been isolated from a malady of cats. This disease can be readily recognized and differentiated from other feline diseases by blood studies, which make apparent the characteristic profound leucopenia and marked relative lymphocytosis in the absence of thrombopenia and appreciable anemia. (Because the cytological pictures of the bone marrow and blood are essentially similar to those which characterize human agranulocytosis, we have named the disease under study "infectious feline agranulocytosis.") The cytological reaction to the presence of the virus is further characterized by proliferation of the reticuloendothelial cells of the lymph nodes and spleen, and by the formation of intranuclear inclusion bodies in the cells of the gastro-intestinal mucosa, lymph nodes, and bronchial mucosa.

The etiological agent, the virus of infectious feline agranulocytosis, is pathogenic for cats when given by the oral, intragastric, cutaneous, subcutaneous, intraperitoneal, intravenous, and intranasal routes; it can be recovered at the height of the disease from the blood, spleen, liver, lung, intestinal mucosa, nasal secretions, nasal mucosa and turbinates, feces, and urine. The virus appears to be limited in its pathogenicity to the feline species. We found that a variety of animals, as represented by albino Swiss mice, guinea pigs, domestic rabbits, and ground squirrels (Citellus richardsonii Sabine), failed entirely to react to the injection of massive doses of virus. Repeated attempts at infection of these animals regularly failed when the intranasal, intraperitoneal, subcutaneous, and intramuscular routes of inoculation were employed for single doses. The same was true when from four to six transfers in "blind" serial tissue passages were made. Moreover, attempts to propagate the virus on the chorio-allantoic membrane of the developing chick were unsuccessful.

The significance of the facts is discussed in the paper that follows.
THE VIRUS OF INFECTIOUS FELINE AGRANULOCYTOSIS
Authors: Lawrence J. S. , Syverton J. T. , Ackart R. J. , Adams W. S. , Ervin D. M. , Haskins A. L. , Saunders R. H. , Stringfellow M. B. , Wetrich R. M.
Published: June 2004

The infection of cats by the virus of infectious feline agranulocytosis is followed by the production of specific neutralizing and protective antibodies, and recovery from the disease is associated with the development of solid immunity to reinfection. From the evidence presented it is obvious that the virus is not related to the viruses of hog cholera, lymphocytic choriomeningitis, fox encephalitis, vesicular stomatitis, the Western type of equine encephalomyelitis, herpes, and B virus infection.
THE SWINE LUNGWORM AS A RESERVOIR AND INTERMEDIATE HOST FOR SWINE INFLUENZA VIRUS
Authors: Shope Richard E.
Published: June 2004

1. The presence of masked swine influenza virus has been demonstrated in lungworm larvae from earthworms dug on Midwestern farms.

2. Swine influenza virus infections were provoked in 2 of 3 swine obtained from an Iowa farm during an interepizootic period.

3. The evidence presented has been interpreted as indicating that the swine lungworm is the reservoir and intermediate host for swine influenza virus in the field.

4. A concept of the epidemiology of swine influenza in which the causative virus is represented as being maintained and disseminated in a masked form by its lungworm intermediate host has been presented.
THE LS-ANTIGEN OF VACCINIA
Authors: Shedlovsky Theodore , Rothen Alexandre , Smadel Joseph E.
Published: June 2004

Studies on LS-protein, the soluble double antigen of vaccinia, and on the degradation products L'S and L''S' have been made with electrophoresis and in the analytical ultracentrifuge.

LS, which is homogeneous electrically and in the ultracentrifuge, has an isoelectric point at pH 4.8. At 4°C. its partial specific volume is 0.72 cc./gm., and its diffusion constant is 1.50 x 10–7 cm.2/sec. The sedimentation constant is 6.35 at 20°C., the molecular weight is 214,000, and the molecule appears to have an elongated ellipsoidal shape with an axis ratio of 1:20.

L'S and L''S' are homogeneous electrically but not in the ultracentrifuge, L''S' being extremely polydisperse.
THE LS-ANTIGEN OF VACCINIA
Authors: Smadel Joseph E. , Hoagland Charles L. , Shedlovsky Theodore
Published: June 2004

Pure LS-antigen of vaccinia contains 15.8 per cent N and 50.6 per cent C. These analytical data together with the absence of lipids, phosphorus, nucleic acid, and glucosamine in preparations of the antigen confirm the protein nature of the substance. The action of proteolytic enzymes on LS offers further confirmation of the protein character of the antigen.

Both the L- and S-activities of the antigen are destroyed by digestion with papain. The effects of crystalline chymotrypsin on LS-antigen are particularly interesting for, under proper conditions, this enzyme destroys the serological activity of the S-portion of the molecule without affecting the L-portion. This newly prepared degradation product of LS, called LS'', contains the same amount of N as the native substance but unlike LS, it forms needle-shaped crystalloids.
ALLERGENIC RELATIONSHIP OF THE POLLENS OF DWARF AND GIANT RAGWEED TO SEVERAL OF THEIR BOTANIC RELATIVES
Authors: Simon Frank A.
Published: June 2004

Thirty-eight of forty patients, allergic to the pollen of dwarf and giant ragweed, were found to be allergic also to the pollen of botanically related species. There was definite variation in the degree of reactivity to the various pollens in different patients. One additional patient reacted to dwarf ragweed but not to giant ragweed or to four other composites.

Antibody neutralization studies in six cases indicated that (a) in four cases dwarf ragweed could have been the only sensitizing allergen. (b) In one case either dwarf or giant ragweed could have been the only sensitizing allergen. (c) In one case cosmos plus either of the ragweeds or some undetermined pollen could have been the sensitizing allergen, (d) In none of the six cases studied could cosmos, sunflower, goldenrod, or dandelion have been the only sensitizing allergens.

The evidence presented supports the following concepts: (1) Hypersensitiveness of this type develops as the result of allergenic stimulation. (2) The pollens of the ragweeds and their botanic relatives contain, in addition to species-specific allergens, multiple common allergenic determinants which vary in their distribution among related species. (3) A person exposed simultaneously to a group of allergens may become sensitized to certain members of the group and not to others, while another person, exposed to the same group of allergens, may become sensitized to different members of the group.
THE ULTRACENTRIFUGE AS AN AID IN THE DETECTION OF POLIOMYELITIS VIRUS
Authors: Melnick Joseph L.
Published: June 2004

1. By means of differential ultracentrifugation, a purified and concentrated macromolecular fraction has been regularly obtained from infected human, monkey, and chimpanzee stools. This fraction was isolated from sixteen stools in which virus was thought to be present, and inoculated intracerebrally into sixteen monkeys, of which fifteen developed poliomyelitis.

2. Eleven stool specimens in which virus was suspected, when tested separately in eleven monkeys by the intra-abdominal-intranasal method, produced poliomyelitis in two of these animals. When the same specimens were tested separately by the ultracentrifugal-intracerebral method, poliomyelitis developed in ten monkeys out of eleven inoculated.

3. With the intra-abdominal-intranasal method, it has been customary to inoculate the virus present in 1.6 gm. of stool. With the ultracentrifugal-intracerebral method, the virus present in as much as 30 gm. of stool has been inoculated.

4. From one titration experiment it would appear that the ultracentrifugal-intracerebral method is at least 100 times more sensitive than the intra-abdominal-intranasal method.
TEN AMINO ACIDS ESSENTIAL FOR PLASMA PROTEIN PRODUCTION EFFECTIVE ORALLY OR INTRAVENOUSLY
Authors: Madden S. C. , Carter J. R. , Kattus A. A. , 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 protein intake is controlled and limited. Such dogs are outwardly normal but have a lowered resistance to infection and to certain intoxications.

When the protein intake of such dogs is completely replaced by the growth mixture (Rose) of crystalline amino acids, plasma protein production is excellent, weight and nitrogen balance are maintained. This growth mixture consists of ten amino acids, threonine, valine, leucine, isoleucine, tryptophane, lysine, phenylalanine, methionine, histidine, arginine, and is as effective as most diet proteins in plasma protein production.

The above amino acid mixture in aqueous solution may be given by vein with equally good plasma protein production and no apparent clinical disturbance even when given rapidly.

Cystine may replace methionine in the above mixture with equally good plasma protein production for 7 to 10 days but at the expense of the body tissues, that is, with weight loss and a negative nitrogen balance.

The addition of cystine to the protein-free, otherwise adequate diet may result in the production of considerable new plasma protein during a period as long as 1 week (cystine effect). This reaction may depend upon the amino acid constitution of the preceding diet protein in that it occurred following a liver feeding but did not occur after pancreas feeding.

Arginine is required in the diet of the protein depleted dog for fabrication of plasma protein. It is apparently not needed for nitrogen balance for as long as 1 or 2 weeks.

The omission of either threonine or valine from the growth mixture is quickly followed by a sharp decline in plasma protein formation and by a negative nitrogen balance.

When histidine, arginine, and most of the lysine are omitted from the growth mixture, nitrogen balance and weight may be maintained for as long as 1 week but plasma protein production falls off markedly.

The findings indicate that the growth mixture of amino acids should be a valuable addition to transfusion and infusion therapy in disease states associated with deficient nitrogen intake or tissue injury and accelerated nitrogen loss, including shock, burns, and major operative procedures.
STUDIES ON EXPERIMENTAL HYPERTENSION
Authors: Goldblatt Harry , Kahn Joseph R. , Lewis Harvey A.
Published: June 2004

Persistent hypertension has been produced in the goat and sheep by constriction of the main renal arteries. The presence or absence of accompanying uremia depends upon the degree of constriction of the renal arteries.

In both sheep and goat, constriction of one main renal artery also caused elevation of the blood pressure which tended to persist longer than in the dog. Excision of the one kidney with main renal artery constricted resulted in a prompt (24 hours) return of the blood pressure to normal.

In the animals with hypertension of long duration but without renal excretory insufficiency, (the "benign" phase) no significant arterio- or arteriolosclerosis developed as a result of the hypertension alone. In the animals that had both hypertension and renal excretory insufficiency, (the "malignant" phase) the typical terminal arteriolar lesions developed in many organs. These lesions consisted of necrosis and fibrinoid degeneration of arterioles and necrotizing arteriolitis which should not be confused with arteriolosclerosis.

The same humoral mechanism which is responsible for experimental renal hypertension in the dog and other animals also obtains in the pathogenesis of experimental renal hypertension in the sheep and goat.
STUDIES ON EXPERIMENTAL HYPERTENSION
Authors: Goldblatt Harry , Katz Yale J. , Lewis Harvey A. , Richardson Evelyn
Published: June 2004

A simple, rapid method for the bioassay of renin has been presented. Reliable and consistent results are obtained by this method whereby an arbitrary dog unit of renin has been established.

The response of normal unanesthetized dogs to renin is independent of the body weight of dogs weighing between 10 and 25 kilos. An estimate of potency of renin per kilo of body weight of the test animals is therefore not only unnecessary but misleading.

A dog unit of renin has been defined as that amount which raises the blood pressure at least 30 and not more than 35 mm. Hg within 3 minutes in at least three unanesthetized dogs. The potency is expressed as dog units of renin per cubic centimeter.

The determination of the amount of renal substance represented by a cubic centimeter of extract and the number of dog units per cubic centimeter give an estimate of the yield of renin which can be expressed as dog units of renin per gram of original renal tissue.

By determination of the number of dog units per cubic centimeter and the amount of nitrogen in milligrams per cubic centimeter in any renal extract the purity of the renin can be determined and expressed as dog units of renin per milligram N.

The establishment of a standard method for the bioassay of renin is considered highly desirable and the method outlined in this paper is suggested for this purpose.
HEMOGLOBIN AND PLASMA PROTEIN
Authors: Robscheit-Robbins F. S. , Miller L. L. , Whipple G. H.
Published: June 2004

Given healthy dogs, fed abundant iron and protein-free or low protein diets, with sustained anemia due to bleeding, we can study the capacity of these animals to produce simultaneously new hemoglobin and plasma protein.

The reserve stores of blood protein producing materials in this way are very largely depleted, and levels of 6 to 8 gm. per cent for hemoglobin and 4 to 5 gm. per cent for plasma protein can be maintained for considerable periods of time. These dogs are very susceptible to infection and to injury by many poisons.

Under such conditions, these anemic and hypoproteinemic dogs will use very efficiently a variety of digests (serum, hemoglobin, and casein) and the growth mixture (Rose) of pure amino acids. Nitrogen balance is maintained and considerable new blood proteins are produced.

Dog plasma by vein is used freely in these doubly depleted dogs to make new hemoglobin in abundance (Table 1). Serum digests by vein are well utilized to make new hemoglobin and plasma protein in the same dogs (Table 1). Serum digests by mouth are effectively used to make new blood proteins (Table 5).

Dog or sheep hemoglobin given in large amounts intraperitoneally are remarkably well utilized to form hemoglobin and plasma protein (Table 6). It must be obvious that the globin of the hemoglobin is saved in these protein-depleted dogs and used to make large amounts of hemoglobin and plasma protein.

Hemoglobin digests are also well utilized whether given by mouth (Table 7) or by vein (Table 8) and liberal amounts of plasma protein are manufactured from digests presumably ideally suited for hemoglobin production.

Casein digests are well used (Table 8) and form as much new plasma protein as any material tested—even serum digests.

Amino acid mixtures are of especial interest. The growth mixture of 10 amino acids (Rose) is well utilized by mouth or by vein and favors new hemoglobin production more than any material tested (Table 2). Cystine replacing methionine in the amino acid mixture increases the plasma protein—hemoglobin output ratio, that is it favors plasma protein production.

Digests of various sorts and amino acid mixtures or combinations of digests and amino acid mixtures can be used rapidly and effectively to build new hemoglobin or plasma protein, to maintain nitrogen equilibrium, and to replete reserve protein stores. These experiments point to clinical problems.

The unexplained preference given to hemoglobin production in these hypoproteinemic dogs is observed under all conditions, even when whole plasma or serum digests are given by vein. In general, 2 to 4 gm. of hemoglobin are formed for every gram of plasma protein.

This all adds up to a remarkable fluidity in the use of plasma protein or hemoglobin which can contribute directly to the body protein pool from which are evolved, without waste of nitrogen, the needed proteins, whether hemoglobin, plasma protein, or tissue proteins.
FURTHER STUDIES ON THE SURVIVAL AND DEVELOPMENT IN VITRO OF A MALARIAL PARASITE
Authors: Trager William
Published: June 2004

The survival of Plasmodium lophurae in vitro is favored by the presence of calcium pantothenate (0.02 mg. per ml). Survival of about 2 weeks in vitro at 40–41°C. has been obtained under the following conditions: a medium consisting of duck red cell extract in balanced salt solution with glutathione and glucose or glycogen, serum, embryo extract, and calcium pantothenate; daily replacement of about half of the medium with fresh medium; addition of fresh uninfected erythrocytes every 2nd day; gentle agitation of the preparation on a rocking machine. In some of these preparations significant increases in male gametocytes and, more rarely, in total numbers of parasites occurred during the first few days.
BIOCHEMICAL STUDIES ON THE VIRUS AND THE INCLUSION BODIES OF SILKWORM JAUNDICE
Authors: Glaser R. W. , Stanley W. M.
Published: June 2004

Silkworm jaundice virus is stable only between pH 5 and about pH 9. The fact that polyhedral bodies retain virus activity after exposure to hydrogen ion concentrations as high as pH 2 is regarded as being due to the protection of virus occluded within the bodies. Further evidence on this point is furnished by experiments on the activity of the polyhedra when treated with antiformin-formalin and when treated with 1 per cent sodium dodecyl sulfate. Free jaundice virus is inactivated by 36 per cent urea, 36 per cent guanidine, or 1 per cent sodium dodecyl sulfate. A purified preparation, active at a concentration of 10–12 gm. per cc., consisting essentially of a nucleoprotein component having a sedimentation constant of 17 S, a particle diameter of 10 mµ, and a molecular weight of about 300,000, was obtained from the polyhedra-free blood of jaundiced silkworms. However, a component having a sedimentation constant of 16 S was demonstrated in the blood of normal worms. This component, the material from diseased blood, and polyhedral bodies, were found to contain serologically related material. Absorption of material from diseased blood with antiserum induced by a preparation from normal blood yielded a substance having a sedimentation constant of 17 S, which reacted strongly only with antiserum to material from diseased blood. This fact, and especially the fact that the inoculation of normal blood does not produce jaundice, demonstrates that a difference must exist between the purified material from diseased worms and that from normal ones. Chemical analyses of the purified virus material and of the polyhedral bodies also showed certain differences, although both probably represent nucleoproteins. Examination by means of the electron microscope showed further differences.
THE DETECTION OF POLIOMYELITIS VIRUS IN FLIES COLLECTED DURING EPIDEMICS OF POLIOMYELITIS
Authors: Trask James D. , Paul John R. , Melnick Joseph L. ,   With the Technical Assistance of John T. Riordan and Marshall Bishop
Published: June 2004

1. A series of 19 different samples of flies collected within epidemic areas during and after the onset of nearby human cases of poliomyelitis have been tested for the virus of poliomyelitis. Four of these samples proved positive.

2. Methods used in collecting the flies, preparing the inocula, and examining the inoculated monkeys (and other animals) are described.

3. All of the positive tests were obtained by the intranasal and intra-abdominal inoculation of Java (cynomolgus) monkeys. Green African and rhesus monkeys represented the smaller number of other monkeys used in which only negative results were obtained.

4. All of the positive samples (as well as nearly all the negative ones) contained "blow flies," and green bottle flies.
THE INFLUENCE OF BIOTIN UPON SUSCEPTIBILITY TO MALARIA
Authors: Trager William
Published: June 2004

Biotin-deficient chickens and ducks developed much more severe infections with Plasmodium lophurae than did non-deficient control animals. While a very mild degree of biotin deficiency sufficed to increase susceptibility, even an extreme degree of pantothenic acid deficiency had no effect. Biotin deficiency also increased the susceptibility of ducks to P. cathemerium. In animals infected with P. lophurae, the concentration of biotin in the plasma as well as in the red cells rose during the course of the infection, reached a peak at about the same time as the parasite number reached its peak, and then returned to normal as the infection subsided. While the administration of additional biotin to animals partially deficient in biotin could be considered a specific measure tending to lessen the severity of infection with P. lophurae, the injection of biotin into animals fed a diet adequate in this vitamin had no antimalarial effects, perhaps because the excess biotin was rapidly removed from the blood.
STUDIES ON THE SITE OF ANTIBODY FORMATION IN RABBITS FOLLOWING INTRACUTANEOUS INJECTIONS OF PNEUMOCOCCUS OR OF STREPTOCOCCUS VACCINE
Authors: deGara Paul F. , Angevine D. Murray
Published: June 2004

1. The antibody response of rabbits following intracutaneous injections of pneumococcus or of streptococcus vaccines showed three phases.

(a) Within 5 to 12 days following a single injection of pneumococcus or of streptococcus vaccine, high antibody titres were detected in extracts from the site of the injection into the skin, the spleen, the bone marrow, and the liver. Occasionally, antibodies were also found in the draining lymph nodes. During this first phase, the titre of the circulating antibodies was low or negative. (b) During the next phase, when the interval between antigen injection and antibody titrations was prolonged from 2 to 4 weeks, the titres of the blood and of the organs showed only slight differences. High titres were observed during this period in extracts from the injected parts of the skin. (c) After a still longer interval during a third phase of antibody response, the serum titre decreased more rapidly than the titre of the extracts from spleen, bone marrow, and injected skin.

2. Similar results were obtained in rabbits following repeated intracutaneous injections of the vaccines. In these rabbits, however, antibodies usually were not detected during the first phase in extracts from the site of the injection into the skin. The repeated injections of the antigen had perhaps neutralized locally formed antibodies and interfered with their detection until an excess of antibodies was produced. No antibodies were found in the lymph nodes of the rabbits that had received repeated injections of vaccines.

3. The antibody titre of the kidney, anterior wall of the stomach, and non-injected parts of the skin was negative or very low.

4. The demonstration of antibodies in extracts from the site of the injection of antigen into the skin and their presence in lymph nodes before they are demonstrable in the blood shows that they are formed at the local site of inflammation. At the same time antibodies are formed in organs that fix antigen, namely in spleen, liver, and bone marrow.
STUDIES IN SENSITIZATION TO SKIN
Authors: Hecht Rudolph , Sulzberger Marion B. , Weil Harry
Published: June 2004

1. Techniques for the preparation of skin antigen suitable for intramuscular injection in rabbits, and of skin antigens (autolysate) for serological experiments are described.

2. A method was evolved which produced a soluble skin antigen (autolysate) suitable for performing precipitin tests.

3. Injection of the rabbit skin antigen and of staphylococcus toxin in rabbits resulted in the formation of antibodies (precipitins) to homologous skin.

4. When homologous skin alone was injected into rabbits, the antibody formation was questionable, or at most, slight.

5. The injection of staphylococcus toxin alone resulted in antibody formation, this antibody being specific for the toxin and not reacting with broth.

6. By utilization of the synergistic action of staphylococcus toxin and of homologous skin antigen, it has been possible for the first time to produce specific antiskin antibodies in experimental animals.