bluuebunny/crossref_metadata_2025 huggingface dataset:
VENEZUELAN EQUINE ENCEPHALOMYELITIS IN MAN
Authors: Casals J. , Curnen Edward C. , Thomas Lewis
Published: June 2004

A filterable agent was isolated from the blood and from washings of the upper respiratory passages of a young laboratory worker during a mild, acute, febrile illness. This agent was identified as a strain of Venezuelan equine encephalomyelitis virus. Circulating specific complement-fixing and neutralizing antibodies not present in sera withdrawn during the acute phase of illness were demonstrated in sera obtained during convalescence. A fellow laboratory worker who became similarly ill simultaneously also developed during convalescence specific circulating antibodies not present prior to illness.
ANTIGENIC PROPERTIES OF NATIVE AND REGENERATED HORSE SERUM ALBUMIN
Authors: Erickson John O. , Neurath Hans
Published: June 2004

Comparative immunological measurements have been carried out on crystalline horse serum albumin in the native state and after regeneration from 8 M urea solutions. The mean antigenic activity of the regenerated protein has been found to be less than 10 per cent of that of the native, whereas both antigens proved to be immunologically equivalent. The problem of the relation between protein denaturation and immunological activity has been considered and discussed on the basis of known physical and chemical differences between native and denatured protein.
THE INFLUENCE OF AGE OF HOST AND TEMPERATURE OF INCUBATION ON INFECTION OF THE CHICK EMBRYO WITH VESICULAR STOMATITIS VIRUS
Authors: Sigurdsson Björn
Published: June 2004

Chick embryos after 7 days of incubation were found to be much more susceptible to infection with vesicular stomatitis virus than were 10 day embryos. They had a 100 per cent mortality and were very suitable for titrations of the virus. The rate of increase of virus in 7 and 10 day embryos was studied. Two different temperatures of incubation were employed, 35–36°C. and 39–40°C., and the growth curves for the virus under the different conditions are presented. 10 day embryos were highly resistant and at 39–40°C. more than half of them survived. At the lower temperature of incubation, 35–36°C., all 10 day embryos died, but they survived much longer than did 7 day embryos.

In the 7 day embryos death occurred after about 12 hours at 39–40°C. and after about 16 hours at 35–36°C., or earlier at the higher temperature.

In embryos of both ages the virus titer reached at the higher temperature was only about 1 per cent of that reached at 35–36°C., even in those that died.
SYNERGISTIC ACTION OF HEMOPHILUS INFLUENZAE SUIS AND THE SWINE INFLUENZA VIRUS ON THE CHICK EMBRYO. II
Authors: Bang Frederik B.
Published: June 2004

Blood cultures of embryos killed by the synergistic action of swine influenza virus and Hemophilus influenzae suis are consistently negative, and embryos infected with swine influenza virus may be killed both by filtered extracts of frozen and dried Hemophilus and by suspensions of heat-killed bacteria. The addition of Hemophilus to the chorioallantoic membrane of embryos infected with swine influenza virus causes the virus to spread from the membrane to the allantoic fluid and embryo. This spreading effect also obtains when a purified preparation of hyaluronidase is used instead of Hemophilus, but it is unaccompanied by a comparable increase in mortality. It is probable that the spread of the virus produced by the bacteria is only partly responsible for the development of the complex infection and that products of these organisms other than the spreading factor play a large part in the mortality of embryos receiving the combination of virus and bacterium.
FURTHER STUDIES ON THE TITRATION AND NEUTRALIZATION OF THE WESTERN STRAIN OF EQUINE ENCEPHALOMYELITIS VIRUS IN TISSUE CULTURE
Authors: Huang C. H.
Published: June 2004

1. Titration and neutralization of the Western strain of equine encephalomyelitis virus can be carried out in vitro by means of tissue culture.

2. The in vitro titration test as presented is a more sensitive method than animal inoculation.

3. Tissue culture may be better than animal inoculation for the detection of small amounts of virus.

4. The neutralization obtained in tissue culture is 100 to 1,000 times greater than that observed in the intracerebral test in mice and is comparable to the potency obtained by the intraperitoneal route of inoculation.

5. The possibility of applying this method to the study of other viruses, known and unknown, is discussed.

6. Further applications of the method described above to evaluation and standardization of bacterial toxins and antitoxins and to the testing of the toxicity of biological and chemical products are suggested.

7. Evidence for the reactivation in vitro as well as in vivo of virus in neutral mixtures by dilution is presented.
TYPING GROUP A HEMOLYTIC STREPTOCOCCI BY M PRECIPITIN REACTIONS IN CAPILLARY PIPETTES
Authors: Swift Homer F. , Wilson Armine T. , Lancefield Rebecca C.
Published: June 2004

A method is described for performing type-specific anti-M precipitin tests on group A hemolytic streptococci in 1 mm. capillary pipettes. These tests require so much less precipitating serum than was formerly used that the method now seems to be practical.
INCREASED RESISTANCE TO VIRAL INFECTION AS A RESULT OF INCREASED FLUID IN TISSUES
Authors: Taylor Haywood M. , Sprunt Douglas H.
Published: June 2004

Experiments are described in which it is shown that the estrogenic hormone (α-estradiol propionate) increases the amount of extracellular fluid in the skin. Since previous work showed that this hormone increases resistance of rabbits to vaccinia virus, it is suggested that the increased resistance is the result of increased fluid in the tissues.

In further test of this thesis, experiments were performed in which the extracellular fluid in the skin was increased by the intraperitoneal injection of a salt solution known to increase the hydration of the tissues. Under these conditions it was found that the spread of India ink in the skin, as well as susceptibility to viral infection, was decreased in the same magnitude as obtains when the animals are treated with estrogenic hormone. The identity of effects under the two sets of circumstances seems to warrant the conclusion that in both instances the spread of India ink and decreased susceptibility to vaccinia are due to the common factor of increased volume of the extracellular fluid.
THE ELIMINATION OF ADMINISTERED ZINC IN PANCREATIC JUICE, DUODENAL JUICE, AND BILE OF THE DOG AS MEASURED BY ITS RADIOACTIVE ISOTOPE (Zn65)
Authors: Montgomery M. Laurence , Sheline G. E. , Chaikoff I. L.
Published: June 2004

The excretion of intravenously injected labeled zinc into pancreatic juice, duodenal juice, and bile of the dog was investigated. The use of the radioactive isotope permitted the injection of minute amounts of zinc, amounts that were negligible when compared with the total amount of zinc already present in the animal.

1. A large proportion of the injected Zn65 was eliminated by way of the external secretion of the pancreas. As much as 11 per cent was excreted in the pancreatic juice in 14 days.

2. Very little of the administered radiozinc appeared in the bile. The maximum excretion observed for this pathway was 0.4 per cent in 8 days.

3. Radiozinc was also found in large amounts in the juice obtained from an isolated loop of the duodenum.
THE MULTIPLICATION OF BACTERIOPHAGE IN VIVO AND ITS PROTECTIVE EFFECT AGAINST AN EXPERIMENTAL INFECTION WITH SHIGELLA DYSENTERIAE
Authors: Dubos René J. , Straus June Hookey , Pierce Cynthia
Published: June 2004

1. Anti-Shiga bacteriophage injected into the general circulation can multiply in the brain of mice infected intracerebrally with Shigella dysenteriae.

2. Under proper conditions, the injection of active bacteriophage into the general circulation can protect mice against an otherwise fatal intracerebral infection with Shigella dysenteriae.

3. The protection so induced appears to depend upon the early establishment of a high bacteriophage level in the infected animal.
THE IMMUNOLOGICAL RESPONSE TO INFLUENZA VIRUS INFECTION AS MEASURED BY THE COMPLEMENT FIXATION TEST
Authors: Friedewald William F.
Published: June 2004

A quantitative complement fixation test with influenza immune sera and virus antigens obtained from allantoic fluid is described. The method utilizes a photoelectric densitometer which provides a simple, objective, and accurate determination of the hemolytic reaction. The enhancement of the hemolytic activity of complement in the presence of serum or allantoic fluid necessitates a preliminary titration of complement in the presence of these agents. An accurate appraisal of the activity of the complement under the conditions of the actual test permits the selection of an optimal amount of complement and greatly increases the sensitivity of the test. The substance (or substances) responsible for the enhanced hemolytic activity of complement has been found in human and many animal sera and in allantoic fluids obtained from the developing chick embryo. It requires the presence of both complement and hemolysin, resists heating at 100°C. for 2 hours, and is dialyzable.

Allantoic fluid or mouse lung preparations of influenza virus contain a complement-fixing antigen which is intimately associated with the virus particle. It sediments in the high speed centrifuge at the same rate as the hemagglutinin and infective particle and, like the latter, is adsorbed by fowl red blood cells and eluted from the cells on standing at room temperature or 37°C. It cannot be separated from the virus particle by repeated washings in the centrifuge or repeated adsorptions with red blood cells; the hemagglutinin and complement-fixing antigen titers remain roughly proportional. This antigen shows a high degree of strain specificity in cross complement fixation tests with PR8, W.S., and swine ferret antisera, and, as found with the neutralization test, it shows little or no strain specificity with human sera. A soluble antigen is also present in influenza virus preparations which can be readily separated from the virus particle by centrifugation. It is not adsorbed by red blood cells. Furthermore, it reacts in lower titer with ferret antisera and usually shows less strain specificity in cross complement fixation tests. In general, allantoic fluid virus preparations contain much less of the soluble antigen than mouse lung extracts.
A KINETIC ANALYSIS OF THE RENIN-ANGIOTONIN PRESSOR SYSTEM AND THE STANDARDIZATION OF THE ENZYMES RENIN AND ANGIOTONASE
Authors: Plentl Albert A. , Page Irvine H.
Published: June 2004

The physicochemical background of the renal vasporessor system (renin-renin-substrate, angiotinin, angiotonase) is given. The formation and destruction of angiotonin is shown to consist of two consecutive reactions, both of which follow the laws of first order kinetics. Each reaction was studied separately and its reaction constant found to be proportional to the enzyme concentration. Hence these constants should be used to express the activity of the enzymes, renin and angiotonase.

The over-all reaction of a mixture of renin and angiotonase such as occurs in kidney extracts with the α-globulin fraction of serum, viz., rapid increase followed by a slow decline in angiotonin concentration, was found experimentally to correspond closely to the theoretical values calculated for such a reaction. The curve obtained also satisfyingly explains the characteristic pressor response to the intravenous injection of renin. An accurate method for the determination of renin in the presence of angiotonase is presented.
A FILTERABLE VIRUS CAUSING ENTERITIS AND PNEUMONIA IN CALVES
Authors: Baker James A.
Published: June 2004

An infectious disease of calves has been described which is characterized by fever, diarrhea, and pneumonia, followed soon by recovery. On autopsy of animals killed at the height of the disease, there is found a catarrhal enteritis and a bronchopneumonia that is usually confined to the anterior lobes of the lungs. From this disease an agent has been secured by the serial inoculation of lung extracts that produces a pneumonia in white mice. Attempts to demonstrate by the same means a similar agent in uninoculated mice from the same stock have yielded negative results. Suspensions of the lungs of the mice with pneumonia, when inoculated intranasally or intratracheally into calves, cause a disease like the natural infection, characterized by fever, diarrhea, and pneumonia. In two experiments pen contact of normal calves with calves inoculated with the passed material resulted in the typical disease. Early in its course the causative agent is found only in the lungs and intestines, but at its height is generally distributed throughout the body. Calves that have recovered from the induced disease are resistant to subsequent infection and their blood serum will neutralize the causative agent as not previously. Sera from calves that have recovered from the natural disease also neutralize the agent. Cultures from the infected lungs of calves and mice as a rule show no growth, and material that has been passed through Berkefeld N filters produces the characteristic disease. It is therefore concluded that this disease of calves is caused by a filterable virus.
WATER METABOLISM IN HYPERTENSIVE RATS
Authors: Oster Kurt A. , Martinez Oscar
Published: June 2004

The water intake in hypertensive rats was investigated. Rats made hypertensive by renal ischemia increased their water consumption by 75 per cent over the preoperative level. Polyuria was associated with this polydipsia and the independence of these occurrences from a number of other factors was demonstrated.

It was found that the presence of a normal kidney exerted a compensatory influence which may mask either hypertension or polyuria or both. The appearance or exacerbation of the changes upon removal of the normal kidney, on the one hand, and the elimination or mitigation of the symptoms upon removal of the ischemic kidney on the other support the view that the changes observed cannot have been due to passive elimination of the kidney tissue by ischemia, but to active malfunction of the renal, and especially the tubular, mechanism upon withdrawal of oxygen. The view is put forward that polyuria is a primary sequel of ischemia rather than secondary to the intra- and extrarenal effects of hypertension. A number of concomitant observations are in harmony with this hypothesis.
POLIOMYELITIS IN THE CYNOMOLGUS MONKEY
Authors: Faber Harold K. , Silverberg Rosalie J. , Dong Luther
Published: June 2004

1. Cynomolgus monkeys were subjected to a series of non-traumatic exposures of the mucous membranes of the alimentary tract, designed to test the relative permeability to poliomyelitis virus of its upper and lower portions.

2. In the first stage, dried poliomyelitis virus of tested potency was administered in fat-covered capsules to 26 monkeys in such a way as to avoid contamination of the oropharynx but to permit thorough exposure of the gastro-intestinal mucosae. No clinical evidence of poliomyelitic infection appeared.

3. Subsequent application of small amounts of virus to the tongues of 18 of the same monkeys caused paralytic poliomyelitis in one of them.

4. Virus given subsequently by enema to 11 of the monkeys caused no clinical manifestations of poliomyelitis.

5. Of 7 monkeys later treated with virus by oronasal spraying, one developed typical preparalytic signs of infection, and the distribution of lesions indicated that entry had occurred through the afferent nerves of the oropharynx and, possibly, the esophagus.

6. The 6 surviving monkeys were exposed to virus by inhalation. One of them developed paralytic poliomyelitis by olfactory entry. The others appeared to have acquired some resistance to infection.

7. The 5 surviving monkeys were inoculated intracerebrally, as a test of immunity. One of them developed paralytic poliomyelitis. The other 4 showed no clinical signs of infection, but all had typical lesions of varying extent and intensity in the central nervous system.

8. A histological examination of the peripheral nervous ganglia in 12 of the exposed monkeys sacrificed at various stages of the experiments revealed lesions compatible with poliomyelitis in all. Ganglia connected with the head alone (Gasserian, cervical sympathetic) were more constantly and, on the average, more severely involved than the celiac, which is connected only with the intestine.

9. While the celiac ganglion was involved in 7 cases, no evidence was found of the spread of infection from it to the spinal cord.
POLIOMYELITIS IN THE CYNOMOLGUS MONKEY
Authors: Faber Harold K. , Silverberg Rosalie J. , Dong Luther
Published: June 2004

1. Repeated non-traumatic exposures to poliomyelitis virus of the mucous membranes of the upper respiratory tract and of various portions of the alimentary tract in 5 cynomolgus monkeys, extending over a period of 9 to 14 months, were followed by a definite, though limited resistance to intracerebral inoculation to the homologous strain of virus in 4 of them. Only one monkey developed paralysis (20 per cent incidence) and the other 4 remained free of signs and symptoms of the disease. 92 per cent of 25 previously untreated monkeys developed paralysis with the same strain after intracerebral inoculation.

2. Microscopic examination of the central and peripheral nervous systems of the 4 non-paralytic cases revealed in all instances typical lesions in the central nervous system descending from the level of inoculation into the brain-stem but in only 2 into the spinal cord and then only in limited, small areas. Lesions were found in the peripheral ganglia in all animals which corresponded in distribution with the surface membranes previously exposed to virus. No lesions were found in the central nervous system indicative of invasion preceding the intracerebral inoculation.

3. Our observations point to the acquisition by the immune animal, as a result of surface exposure, of the power to limit the spread of infection in the central nervous system rather than of the capacity entirely to prevent implantation and multiplication of virus.

4. This limitation of spread, it is suggested, resembles the tendency so commonly seen in human poliomyelitis of the disease to "halt" at some stage of its evolution, resulting in the various clinical gradations in extent and severity of involvement (subclinical, abortive, non-paralytic, mild paralytic forms, etc.)

5. The experimental methods of exposure, previous to intracerebral inoculation, employed in our study are compared with the natural exposures of human beings during the course of life, which, as age advances, lead to increasing resistance to poliomyelitis and to an increasing incidence of specific neutralizing antibodies in the blood.

6. The mechanism of resistance is obscure. It may be related to the continuing presence of infection in the peripheral ganglia but this is as yet unproved.
THE SEROLOGICAL DIAGNOSIS OF RELAPSING FEVER
Authors: Stein George J.
Published: June 2004

1. Spirochetes of relapsing fever have been separated from the blood of heavily infected mice and rats by hemolysing with saponin, followed by repeated washing of the spirochetal suspension with physiological saline.

2. Spirochetes obtained in this manner appear to have broad antigenic specificity. Antigens of this type fixed complement in the presence of serum obtained from man or animals infected with one or other of the recognized strains or "species" of relapsing fever spirochetes. Macroscopic agglutination of the antigens likewise was observed with sera from the same sources.

3. Positive serological reactions were not observed with convalescent sera obtained following infection with other diseases, for example, typhus fever, malaria, Rocky Mountain spotted fever, Weil's disease, syphilis, and typhoid fever. Hyperimmune sera prepared against other pathogens also failed to react with the relapsing fever antigens.

4. No apparent change in the antigen occurred following storage in the ice box for as long as 4 months.

5. The results indicate that treatment of the spirochetes of relapsing fever with saponin yields a relatively stable antigenic preparation which may prove useful in the serological diagnosis of this disease.
FATAL MURINE TYPHUS INFECTION IN THE dba STRAIN OF MICE, WITH OBSERVATIONS ON STRAIN VARIATION IN SUSCEPTIBILITY
Authors: Moragues Vicente , Pinkerton Henry
Published: June 2004

Injected intracranially in the dba strain of mice, murine typhus rickettsiae caused a serially transmissible meningoencephalitis similar to that produced by psittacosis and certain other viruses. All injected mice of this strain suddenly became ill and approximately half of these animals died on the 5th and 6th days after injection. Swiss mice injected in parallel series showed illness in only a few animals, and no deaths occurred. These experiments were carried out at room temperatures ranging from 60–80°F.

After intraperitoneal injection, a uniformly fatal rickettsial peritonitis developed in all dba mice kept at environmental temperatures of 65–73°F. or 70–80°F. Death occurred between the 3rd and 7th days after injection, depending somewhat on the dosage used. Among Swiss, brown agouti, and A albino mice injected in parallel series, the mortality was less than 60 per cent. These experiments indicate that mice of the dba strain are much more susceptible to murine typhus than are mice of the other three strains studied.
RELATIONSHIP OF THE VIRUS OF LOUPING ILL IN SHEEP AND THE VIRUS OF RUSSIAN SPRING-SUMMER ENCEPHALITIS IN MAN
Authors: Casals J. , Webster L. T.
Published: June 2004

An experimental study of three strains of Russian spring-summer encephalitis virus and one of louping ill virus has yielded the following results:—

1. The sera of mice hyperimmunized to the viruses of Russian encephalitis and louping ill respectively have produced complement fixation with both antigens in almost precisely the same titer.

2. In neutralization tests hyperimmune sera against the Russian virus strains protected against louping ill virus to the same extent as against the Russian virus strains. Conversely, hyperimmune sera against the louping ill virus protected against the Russian viruses, although to a less degree than against louping ill virus.

3. In cross-resistance tests in mice, a vaccine consisting of formolized Russian virus gave strong protection against this latter and moderate protection against louping ill virus. Formolized louping ill virus gave moderate protection against infection with louping ill and considerably less against the Russian virus.

4. Serum from an individual recovered from a laboratory infection with louping ill virus contracted in 1933 gave positive complement fixation and neutralization tests with the Russian spring-summer encephalitis, as well as with louping ill virus.

5. Serum from a patient who became infected with either Russian or louping ill virus or both while working with the viruses in the laboratory in the fall of 1942, gave positive reactions on complement fixation and neutralization tests against them both.

6. No such similarities have been found with other central nervous system viruses. Hence it would appear that they are specific.
STUDIES ON THE ANTIGENIC COMPOSITION OF GROUP A HEMOLYTIC STREPTOCOCCI
Authors: Stewart Walter A. , Lancefield Rebecca C. , Wilson Armine T. , Swift Homer F.
Published: June 2004

1. The occurrence of closely related T antigens in the series composed of types 15, 17, 19, 23, and 30 accounts for most of the cross reactions observed among these types. Similarly T antigens, unrelated to the first series but mutually related, occur in a second series comprising types 4, 24, 26, 28, 29, and 46.

2. Matt variants of each of the eleven types studied possess type-specific M antigens demonstrable either by precipitin or agglutinin reactions.

3. In seven of these types, strains have been encountered which do not possess the T antigen usually associated with the type in question.

4. Procedures are outlined in the appendix for preparing specific antisera for the classification of these types by the slide agglutination technique.
DEPRESSION OF ANAEROBIC GLYCOLYSIS OF EMBRYONIC TISSUE BY WESTERN STRAIN OF EQUINE ENCEPHALOMYELITIS VIRUS. PREVENTION OF THIS EFFECT BY SPECIFIC IMMUNE SERUM
Authors: Victor Joseph , Huang C. H.
Published: June 2004

Studies were made on the effect of mixing the Western strain of equine encephalomyelitis virus (W.E.E.) and embryonic tissue on the rate of anaerobic glycolysis of the tissue. Whole chick embryo, chick embryo from which brain and spinal cord had been removed, and embryonic skeletal muscle were employed.

1. W.E.E. virus depressed the rate of anaerobic glycolysis of embryonic tissues within 2 days after its addition to the tissue. The decrease in anaerobic glycolysis varied from 17 to 82 per cent and was apparent 2 to 4 days after the addition of the virus. No significant effect of the virus was observed 4 hours and 6 days after mixing it with the tissue.

2. Anti-W.E.E. immune serum prevented the inhibiting action of W.E.E. virus on the anaerobic glycolysis of embryonic skeletal muscle.
A STUDY OF CONDITIONS FOR THE OPTIMUM PRODUCTION OF PR8 INFLUENZA VIRUS IN CHICK EMBRYOS
Authors: Miller Gail Lorenz
Published: June 2004

In order to determine the conditions for the optimum production of PR8 influenza virus in chick embryos, a study has been made of the róles of concentration of virus in the inoculum, temperature of incubation of infected embryos, length of time of incubation of infected embryos, and age of embryos at the time of inoculation. Relative amounts of virus in different preparations were measured indirectly by means of determinations of chicken red blood cell agglutination titers. Frozen infectious allantoic fluid which produced infection in chick embryos at a maximum dilution of 10–7 was employed as a stock inoculum. Best results were obtained with an amount of stock inoculum of 0.1 cc. of a 10–5 dilution, a temperature of incubation of 35°C., a length of time of incubation of 36 to 48 hours, and with embryos brought to 10 or 11 days of age at 37°C. or 9 or 10 days of age at 39°. An uncontrolled factor arising from inherent variations in the properties of different embryos and different batches of embryos was discussed.
THE MOUSE INFECTIVITY TITRATION OF INFLUENZA VIRUS
Authors: Lauffer Max A. , Miller Gail Lorenz
Published: June 2004

A study has been made to establish the statistical significance of results obtained in mouse infectivity titrations of influenza virus. Five titrations, each composed of five replicas, were carried out and 50 per cent end points were calculated for each titration. Three criteria for evaluating the end points were employed, namely, the presence or absence of pulmonary lesions, the occurrence of death, and a weighted composite taking into account both the extent of lung consolidation and the occurrence of death. Standard deviations of the distribution of end points obtained by each method were computed, and from these data levels of probabilities for significance in the differences between end points were determined. It was found that the chances are 19 out of 20 that differences of 0.99, 0.77, and 0.73 logarithmic units, respectively, for the lesion, the death, and the weighted end points are significant.
THE RENAL PATHOLOGY OF NUTRITIONAL HYPERTENSION IN RATS
Authors: Calder Royall M.
Published: June 2004

Rats subsisting on a diet partially deficient in the heat-stable fractions of the vitamin B complex are known to experience a rise in blood pressure. The present study shows that after prolonged administration of this dietary, abnormal structural changes occur in the kidneys. The surface of this organ becomes finely granular. The afferent arterioles show degenerative changes, consisting of irregular subendothelial hyaline deposits which encroach on the lumen. The interlobular arteries undergo the same change, plus degeneration of the media; the lumen of these vessels is likewise compromised. Resultant, small, streak-like areas of ischemic atrophy occur in both cortex and medulla, with necrosis of the epithelial lining of the uriniferous tubules. The glomeruli are reduced in size, the number of their component loops decreased, their pattern simplified, and the capillary basement membrane thickened. In addition to these changes, kidneys from animals on a more profoundly deficient diet display numerous areas of hemorrhagic infiltration in the cortical and subcapsular regions.

The possible identity of these lesions with those seen in essential hypertension in man is discussed.
THE EFFECT OF VITAMIN B1 DEFICIENCY AND OF RESTRICTED FOOD INTAKE ON THE RESPONSE OF MICE TO THE LANSING STRAIN OF POLIOMYELITIS VIRUS
Authors: Foster Claire , Jones James H. , Henle Werner , Dorfman Frieda
Published: June 2004

In several experiments it was shown that a deficiency of vitamin B1 in the diet increased the resistance of mice to the Lansing strain of poliomyelitis. The source of the virus was a suspension of infected mouse brain in saline, which was injected intracerebrally. Both the mortality rate and the incidence of paralysis were lower in the deficient animals than in the normally fed controls. The protection was more pronounced with respect to paralysis than with respect to the number of deaths. Some deaths in the deficient groups were undoubtedly due to the vitamin deficiency, as indicated by numerous deaths among groups of animals which were given the deficient diet but injected with a suspension of normal brain. An attempt was made to maintain a state of chronic vitamin deficiency by giving small amounts of the vitamin. The results also seem to indicate that the effect of the deficiency was more in delaying the action of the virus than in preventing it. The greatest difference between normally fed and deficient animals receiving the virus came at about the 12th day after inoculation.

Comparable results were obtained by restricting the intake of the complete diet to 1 gm. per mouse per day, which is about 40 per cent of the intake of the normally fed mice. Restriction of the caloric intake alone gave similar results. Restriction of food intake was effective in experiments in which extra vitamin B1 was given in the diet and also when a diluted saline solution was given by stomach tube to assure a sufficient intake of fluid.

Other data are necessary before an explanation can be given for the manner in which these deficiencies increase the resistance of the mice to the virus of poliomyelitis.
HEREDITY OF THE Rh BLOOD TYPES
Authors: Wiener Alexander S. , Sonn Eve B. , Belkin Ruth B.
Published: June 2004

Data are presented concerning the Rh blood types in 97 families with 275 children and in 135 mother-child combinations. The results obtained are in complete agreement with the theory of six allelic genes. When the theory is tested by applying the chi square and gene frequency methods to data on the distribution of the Rh types in the population, the agreement is also satisfactory.

The practical implications of the findings are discussed.
AN EVALUATION OF METHODS FOR THE CONCENTRATION AND PURIFICATION OF INFLUENZA VIRUS
Authors: Stanley W. M.
Published: June 2004

The concentration and purification of influenza virus by means of differential centrifugation in a vacuum type centrifuge, by adsorption on and elution from adult chicken red cells, by elution of the precipitate formed on freezing and thawing of allantoic fluid, by adsorption on and elution from embryonic chick red cells, and by combinations of the first method with each of the three succeeding methods, have been studied. Over-all yields of virus of about 50 to 70 per cent were obtained by these methods and combinations of methods except for somewhat lower yields when adsorption on and elution from adult chicken red cells was employed. However, the purified products obtained by methods involving only the use of red cells or the freezing and thawing technique were found to contain about 80 per cent of non-virus protein. The purified products obtained when differential centrifugation was used either alone or in combination with any one of the other methods were found to be indistinguishable and to consist of a fairly homogeneous component having a sedimentation constant of about 600 S. Such preparations possessed about 22,000 chicken red cell agglutinating units per mg. of protein nitrogen and solutions containing only about 10–14 gm. of the materials gave 50 per cent infectivity end points in chick embryos. The Sharples centrifuge was found to be almost as efficient as the vacuum type centrifuge for the concentration and purification of influenza virus and, because of its larger capacity, is recommended for the preparation of purified virus on a large scale.
CENTRIFUGATION AND ULTRAFILTRATION STUDIES ON ALLANTOIC FLUID PREPARATIONS OF INFLUENZA VIRUS
Authors: Friedewald William F. , Pickels Edward G.
Published: June 2004

A synthetic density gradient technique has been applied to the study of the PR8 and Lee strains of influenza virus in the angle centrifuge. The method counteracted convective disturbances and permitted about a fiftyfold improvement in clearing supernatant fluids of virus. Sedimenting boundaries of infective virus particles, hemagglutinin, and complement-fixing antigen were obtained in the angle centrifuge and correlated with boundaries observed optically in the ultracentrifuge. The sedimentation constant of infective Lee virus particles is approximately 800 Svedberg units, while that of PR8 virus is only about 700. On the assumption of spherical shape, these values correspond to approximate diameters of 85 and 80 mµ respectively. These values agree with those obtained by filtration with graded collodion membranes. The concentration of primary virus particles in untreated allantoic fluid preparations of PR8 or Lee virus is of the order of 0.01 per cent.

The primary infective particles are identical with the hemagglutinin and the complement-fixing antigen to a large extent. However, allantoic fluid preparations of PR8 virus also show a slightly inhomogeneous group of particles with an average sedimentation constant of 460 S, which are adsorbed by and eluted from red blood cells yet appear to be non-infective. In addition the virus preparations contain a small amount of "soluble antigen" which sediments more slowly than the virus and is not adsorbed by red blood cells. This soluble antigen is probably associated with material which was observed optically in the ultracentrifuge to sediment at rates ranging from very low values up to that characteristic of the primary virus boundary. This distribution of rate makes it seem likely that the material represents disintegrated virus particles.

Calculations based on the experimental results obtained indicate that of the order of 10 influenza virus particles are required to produce infection of chick embryos or mice with the PR8 virus. While a comparable number is required with Lee virus for infection of chick embryos, about 10,000 particles are necessary for infection of mice. The ratio of hemagglutinin to red blood cells required to produce 50 per cent agglutination with dilute virus suspensions in the standard test is roughly 1.
INTERFERENCE BETWEEN THE INFLUENZA VIRUSES
Authors: Ziegler James E. , Lavin George I. , Horsfall Frank L.
Published: June 2004

Influenza A or influenza B virus rendered non-infective by ultraviolet radiation was found to be capable of producing interference with the multiplication of active influenza viruses in the chick embryo. Certain temporal and quantitative relationships affecting the interference phenomenon with this host-virus system were studied. An hypothesis of the mechanism of interference between the influenza viruses is proposed and discussed.
THERAPEUTIC EFFECTIVENESS OF PENICILLIN IN EXPERIMENTAL MURINE TYPHUS INFECTION IN dba MICE
Authors: Moragues Vicente , Pinkerton Henry , Greiff Donald
Published: June 2004

The administration of penicillin in relatively large but non-toxic doses to dba mice after injection with murine typhus rickettsiae resulted in a marked reduction in mortality, particularly when the initial dosage of rickettsiae was relatively small, approaching the minimal lethal dose. No evidence of secondary bacterial infection was obtained by bacteriological and histological studies, and it seems justifiable to conclude that the greatly increased survival rate in the treated mice was caused by the action of penicillin on typhus rickettsiae. The theoretical and practical implications of the results are discussed.
BLOOD-SUCKING VECTORS OF ENCEPHALITIS: EXPERIMENTAL TRANSMISSION OF ST. LOUIS ENCEPHALITIS (HUBBARD STRAIN) TO WHITE SWISS MICE BY THE AMERICAN DOG TICK, DERMACENTOR VARIABILIS SAY
Authors: Blattner Russell J. , Heys Florence M. ,   With the Technical Assistance of Margaret B. McDonald
Published: June 2004

(1) The common dog tick, Dermacentor variabilis, is capable of being infected with the virus of St. Louis encephalitis, Hubbard strain, by feeding on inoculated animals and, once infected, can transmit the virus to normal susceptible animals by bite. (2) A female can transmit the infection to her offspring, through all stages of metamorphosis of the 2nd generation into the 3rd generation. (3) Ticks infected under laboratory conditions and kept inactive at a temperature of 12.5°C., remained infective for at least a period of 10 months. Eggs laid by an infected female and stored in a refrigerator (12.5°C.) for 10 months retained infective virus, and larvae hatched from such eggs at the end of the 10 months of dormancy were also infective. (4) The present work, a preliminary account of which appeared in December, 1941 (1, 2), is of theoretical significance since in so far as we are aware, it represents the first successful transmission of St. Louis encephalitis to experimental animals by a blood-sucking vector.
TITRATION OF INFLUENZA VIRUS IN CHICK EMBRYOS
Authors: Knight C. A.
Published: June 2004

A study was made to establish the reproducibility of end points obtained in the titration of influenza viruses in chick embryos. Six tests were performed, each composed of five replicate titrations of a purified preparation of the PR8 strain of influenza virus. The data from these titrations were subjected to statistical analysis which revealed that the chances are 19 out of 20 that differences in end points of 0.37 and 0.62 logarithmic units are significant in titrations employing ten embryos and five embryos per dilution, respectively. Additional simultaneous titrations in embryos and in mice showed that chick embryos are sensitive to considerably smaller amounts of virus than are mice, and that the mouse titration is adversely affected by inactive virus under conditions which are without apparent influence on the embryo titration.
METHIONINE PROTECTS AGAINST MAPHARSEN LIVER INJURY IN PROTEIN-DEPLETED DOGS
Authors: Goodell J. P. B. , Hanson P. C. , Hawkins W. B.
Published: June 2004

Depletion of body protein stores by means of low protein diet or plasmapheresis causes greater susceptibility to liver injury by the arsenical compound, mapharsen.

Normal dogs can tolerate mapharsen in doses of 0.006 to 0.008 gm. per kilo whereas in protein-depleted dogs doses of 0.002 to 0.0025 gm. per kilo cause liver injury with jaundice.

Methionine (2 to 4 gm.) given by mouth 20 to 24 hours prior to administration of mapharsen is protective and the dogs will tolerate 0.0045 gm. per kilo with no icterus developing.

Methionine (1 gm.) intravenously just prior to mapharsen injection is not as consistent in effecting protection, but the smaller dose may be responsible.
QUALITATIVE DIFFERENCES IN THE ANTIGENIC COMPOSITION OF INFLUENZA A VIRUS STRAINS
Authors: Friedewald William F.
Published: June 2004

A study of the PR8, Christie, Talmey, W.S., and swine strains of influenza A virus by means of antibody absorption tests revealed the following findings:

1. Serum antibody could be specifically absorbed with allantoic fluid containing influenza virus or, more effectively, with concentrated suspensions of virus obtained from allantoic fluid by high-speed centrifugation or by the red cell adsorption and elution technique. Normal allantoic fluid, or the centrifugalized sediment therefrom, failed to absorb antibodies. Influenza B virus (Lee) caused no detectable absorption of antibody from antisera directed against influenza A virus strains, but it specifically absorbed antibody from Lee antisera.

2. The neutralizing, agglutination-inhibiting, and complement-fixing anti-bodies in ferret antisera were completely absorbed only by the homologous virus strain, even though 2 absorptions were carried out with large amounts of heterologous virus strains.

3. PR8 virus appeared to have the broadest range of specific antigenic components for it completely absorbed the heterologous antibodies in Christie and W.S. antisera and left only those antibodies which reacted with the respective homologous strains. The other virus strains (Christie, Talmey, W.S., swine) were more specific in the absorption of heterologous antibodies and completely removed only those antibodies which reacted with the absorbing virus.

4. The absorption tests revealed a higher degree of specificity and individuality of the virus strains than the various cross reactions previously reported. The strain specificity of PR8 virus was equally manifest in absorption tests with ferret sera and with human sera following vaccination.

5. The amount of homologous antibody remaining in a PR8 ferret serum after absorption with PR8 virus, obtained by the red cell adsorption and elution method, varied inversely as the concentration of virus used for absorption. A given concentration of virus, however, absorbed a greater percentage of neutralizing antibodies than either agglutination-inhibiting or complement-fixing antibodies.
THE SIGNIFICANCE OF ANTIGENIC DIFFERENCES AMONG STRAINS OF THE "A GROUP" OF INFLUENZA VIRUSES
Authors: Magill Thomas P. , Sugg John Y.
Published: June 2004

"Acute" and "convalescent" samples of serum from 40 patients from a localized outbreak of influenza were tested for mouse-protective antibodies against 7 different strains of influenza virus, which included 2 laboratory strains representative of "group A" and of "group B," and 5 strains from the investigated outbreak. The latter 5 strains although not identical were related to each other and to the PR8 strain. The chief point shown by the data was the considerable degree of antigenic difference among the 6 "group A" strains, evidenced by the marked differences in the protective capacities of the serums when tested against the various strains.

A number of the "acute" serums showed high protective capacity against some strains but relatively little protective capacity against other strains. In the 5 instances in which it was possible to test the "acute" serums against strictly homologous strains of virus, no protective capacity was demonstrable. In 7 of 36 cases, the antibody responses evoked by influenza infections were not detectable by tests with some strains, but were detectable by tests against other related strains.
BILIARY EXCRETION OF RADIOACTIVE IRON AND TOTAL IRON AS INFLUENCED BY RED CELL DESTRUCTION
Authors: Hawkins W. B. , Hahn P. F.
Published: June 2004

Iron is eliminated in the bile of normal dogs at a low but quite constant rate, 0.2 mg. per day. The feeding of large amounts of iron to normal dogs does not cause an increased iron excretion in the bile nor does the injection of considerable quantities of colloidal iron by vein.

When red cell destruction is brought about by acetyl-phenylhydrazine the elimination of biliary iron may increase tenfold and parallels the increased output of bile pigment.

When red cells containing radioactive iron are destroyed by acetyl-phenylhydrazine there is a significant increase in radioactive iron excreted in the bile which parallels the bile pigment excretion—Charts A and C.

The excretion of iron and bile pigment is independent of the volume of bile.

When hemoglobin is destroyed the pigment radicle is totally excreted as bile pigment but only 3 per cent of the released iron is eliminated in the bile with conservation of the remainder.

The importance of the liver and spleen as storehouses of iron is again confirmed. The body conserves iron even when it is present in marked excess.
CERTAIN CONDITIONS DETERMINING ENHANCED INFECTION WITH THE RABBIT PAPILLOMA VIRUS
Authors: Friedewald William F.
Published: June 2004

The infection of normal or hyperplastic rabbit skin with the papilloma virus can be greatly enhanced by protecting the scarified and inoculated area with a layer of paraffined gauze until healing occurs. In this way the necrosis which follows upon scarification and also the scabbing are almost entirely prevented and in consequence epithelial regeneration is usually complete within 24 hours. Not only are many susceptible cells provided to the virus far earlier than would otherwise be the case,—and collateral tests have shown that it becomes associated with them within a few hours instead of after many,—but the inoculum is itself conserved, instead of becoming largely lost amidst necrotic tissue and scab, as under ordinary circumstances. The effective titer of the virus is increased by the procedure from 10 to 100 times over that attained when hyperplastic skin is allowed to dry after inoculation. Since the results under the latter circumstances are 10 to 100 times better than those when normal skin is treated in the same way it follows that a 100- to 10,000-fold increase in the effectiveness of the virus has now been obtained.
PERITONEAL ABSORPTION
Authors: Hahn P. F. , Miller L. L. , Robscheit-Robbins F. S. , Bale W. F. , Whipple G. H.
Published: June 2004

The absorption of red cells from the normal peritoneum of the dog can be demonstrated by means of red cells labeled with radio-iron incorporated in the hemoglobin of these red cells. Absorption in normal dogs runs from 20 to 100 per cent of the amount given within 24 hours.

Dogs rendered anemic by bleeding absorb red cells a little less rapidly—ranging from 5 to 80 per cent of the injected red cells. Doubly depleted dogs (anemic and hypoproteinemic) absorb even less in the three experiments recorded.

This peritoneal absorption varies widely in different dogs and even in the same dog at different times. We do not know the factors responsible for these variations but there is no question about active peritoneal absorption.

The intact red cells pass readily from the peritoneal cavity into lymph spaces in diaphragm and other areas of the peritoneum. The red cells move along the lymphatics and through the lymph glands with little or no phagocytosis and eventually into the large veins through the thoracic ducts.