bluuebunny/crossref_metadata_2025 huggingface dataset:
Studies on the Protective Effect of Gamma Globulin against Herpes Simplex Infections in Mice
Authors: Cheever F. S. , Daikos George , Sullivan Julia C.
Published: January 2023

Concentrated human serum gamma globulin has been shown to contain virus neutralizing antibody for herpes simplex virus by means of protection tests in which mice were employed. When the globulin was administered prior to the challenge dose of virus the protective effect was definite although slight. No more than a minimal protective effect was observed when the viral injection preceded the administration of globulin by as little as 12 or 24 hours. Porcine and bovine gamma globulin had no demonstrable protective effect. No antigenic relationship between the viruses of herpes simplex and epidemic keratoconjunctivitis was revealed by protection tests with human gamma globulin.
The Action of Enzymes in Hemagglutinating Systems
Authors: Wheeler Warren E. , Luhby A. Leonard , Scholl Mary Louise L.
Published: January 2023

Summary and Conclusion

The nature of the enzymatic action on human red blood cells by weak solutions of certain proteolytic enzymes was studied,particularly with reference to the properties acquired which allow them to be agglutinated by homologous “incomplete” anti-Rh antibodies in saline media. The optimal conditions with respect to trypsin concentration, time, pH, and temperature for the treatment of red cells so that they take on these properties has been discussed. It would appear from the present data that this enzyme modification involves an alteration of the red cell surface to produce both a diminished cell “suspension stability” and a “rearrangement” or “uncovering” of portions of the antigenic moiety. Trypsin-modified red cells have been employed as extremely sensitive indicators for the detection of anti-11h and other blood group antibodies, both complete and incomplete. Agglutination reactions with such cells are specific, easily read,immediate,and unlikely to show failure of agglutination because of serum prozones.
A Nomographic Probit Solution for the Median Effective Dose (ED50)
Authors: Koch Walter , Kaplan Deborah
Published: January 2023

A simple and rapid nomographic probit solution for the median effective dose (ED50) is proposed. ED50 and the slope of the dosage-response curve are directly read off from the same nomogram. Additional nomograms convert death rates into probits, and give estimates of the standard error of ED50, the standard error of the slope, and the standard error of the difference of two assays. A fully worked example is shown.
Agglutinin Response to Intradermal Tests for Sensitivity to the Brucella
Authors: Carpenter Charles M. , Deboer Carl J. , Klein Sidney J. , Tempereau Clinton E.
Published: January 2023

Intradermal tests for sensitivity to the Brucella were made on 193 male patients with negative agglutination tests. Of this number, 136 (70 per cent) were negative and 57 (30 per cent) were positive. Agglutination tests for brucellosis made on the 136 skin-test-negative patients 2 weeks after negative intradermal tests were negative in every instance. Agglutination tests for brucellosis made on 57 patients 2 weeks after a positive intradermal test demonstrated that 17 (30 per cent) developed agglutinins with titres ranging from 1:20 to 1:1280. The agglutinin titre, observed in the sensitized patients after an intradermal test, either disappeared or declined markedly in from 1 to 3 months following the test. Agglutination tests carried out on patients 4 and 6 weeks after the intradermal tests did not detect additional positive reactions. The results of simultaneous intradermal tests with Brucellergen and a diluted Brucella vaccine containing 20 million cells were comparable to those obtained when a single antigen was employed. Complement-fixation and agglutination tests made on normal guinea-pigs 4 weeks following the intradermal injection of 0.1 ml either Brucellin or Brucellergen remained negative. One guinea-pig, however, injected with diluted Brucella vaccine developed complement-fixing antibodies in a serum dilution of 1:16. None of the guinea-pigs acquired dermal sensitivity to the antigens as demonstrated by intradermal tests with Brucellergen.
Studies on Commercial Typhus Vaccines
Authors: Chambers Leslie A. , Cohen Seymour S. , Clawson Jean R.
Published: January 2023

Purified suspensions of epidemic typhus rickettsiae have been disrupted by sonic vibration and fractionated by differential centrifugation, yielding preparations of varying physical, chemical and biological activity. The low speed sediment, representing rickettsial debris largely, yields a turbid suspension containing about half of the total rickettsial nitrogen, demonstrating about half of the in vitro complement fixing activity of the whole rickettsiae, and cross-reacting completely with murine and epidemic typhus antibodies. The high speed sediment yields an opalescent suspension and contains about a third of the original nitrogen, and two-thirds of the original complement fixing activity, with decreased cross-reactivity. The high speed supernate yields a water-clear solution, containing only small amounts of the nitrogen and complement-fixing activity of the whole rickettsiae, and is relatively non-specific in its in vitro antigenic effects.

The low and high speed sediments subjected to proteolytic digestion, yield less turbid suspensions or solutions which lose one-fourth to one-third of their nitrogen in dialysis, but retain the complement fixing activity of the original suspension, with increased cross-reactivity.
Studies on Commercial Typhus Vaccines
Authors: Cohen Seymour S.
Published: January 2023

Rickettsial antigens have been demonstrated to be serologically unrelated to cytoplasmic particles of the host. Data have been presented on some amino acids and lipids found in rickettsial fractions and the S antigen. The demonstration of desoxyribose nucleic acid in R. prowazeki and its approximate estimation has been described, and a new procedure for its isolation in high yield has been recorded. The effect of sonic disruption in the depolymerization of desoxyribose nucleic acid has been noted. The failure to demonstrate ribose nucleic acid in rickettsial fragments has been described and discussed.

It has been observed that rickettsial antigens gave some anomalous color reactions for carbohydrate and showed aldehydic properties. In addition, the orcinol-reactive carbohydrate in various rickettsial fractions was equivalent to the reducing sugar content of these fractions before acid hydrolysis. The structural and possibly practical significance of these findings have been discussed.
The Enhancement of Anaphylaxis in Albino Mice with the Aid of Adjuvants
Authors: Wheeler Albert H. , Brandon Ella M. , Petrenco Helene
Published: January 2023

Summary and Conclusions

A single subcutaneous or intraperitoneal injection of protein antigen incorporated in Freund's adjuvant sufficiently sensitized albino mice so that almost all animals exhibited anaphylactic death or severe shock when subsequently challenged with specific antigen. Stronger anaphylactic responses were obtained with large rather than with small sensitizing doses and with intravenous rather than intraperitoneal injection of the challenge dose. Anaphylactic reactions were fewer and milder when the interval between sensitization and challenge was less than 14 days. Maximum results were obtained when this interval was 21 to 28 days. Fatal anaphylactic reactions occurred with greater frequency in bilaterally adrenalectomized sensitized mice than in nonadrenalectomized sensitized mice. However, a large percentage of adrenalectomized control mice died following challenge with a quantity of antigen that was not lethal to normal animals. The injection of adrenal-cortical extracts shortly prior to the injection of the challenge antigen regularly resulted in a slight reduction in the number of fatal shock reactions. Under the conditions of these experiments it appears that in sensitized pregnant mice, abortion following the injection of a shock dose of antigen is a useful measure of anaphylactic response. The results of these experiments appear to justify a further consideration of utilizing the above findings as the bases for formulating a practical and reliable method for demonstrating active anaphylaxis in albino mice.
The Indirect Complement Fixation, Hemagglutination and Conglutinating Complement Absorption Tests for Viruses of the Psittacosis-Lymphogranuloma Venereum Group
Authors: Hilleman M. R. , Haig D. A. , Helmold R. J.
Published: January 2023

Three new tests for demonstrating antibody against viruses of the psittacosis-lymphogranuloma venereum group are described. These are the indirect complement fixation test, which detects inhibitory antibody for these viruses in the sera of chickens, the hemagglutination inhibition technique for testing human and chicken sera and the conglutinating complement absorption test for use with sera from patients. The possible application of the indirect complement fixation and agglutination inhibition tests to the study of infection with these viruses in avian populations is discussed. The relative merits and demerits of the three tests as compared with the ordinary complement fixation test are also reviewed.

Theoretical considerations regarding the mechanism of the indirect complement fixation test, the nature of the meningopneumonitis hemagglutinin and the inhibition of hemagglutination by calcium ion are discussed.
Observations on the In-Vitro Behavior of Dog Isoantibodies
Authors: Christian Ricilard M. , Ervin Donald M. , Young Lawrence E.
Published: January 2023

Isohemagglutinins having four different specificities have been demonstrated in dog sera. These have been arbitrarily designated anti-A, -B, -C and -D and the corresponding agglutinogens A, B, C and D in the order of their identification in this laboratory. Anti-D has been observed as a naturally occurring antibody while anti-A, -B and -C have been demonstrated only in dogs transfused with erythrocytes containing the respective factors. Many variants of the A agglutinogen exist and these have been designated A′. The A-A′ differences are partly qualitative in nature and are thought to resemble human D-Du differences more closely than human A1-A2 differences. The following properties of anti-A, -B, -C and -D have been described: thermal amplitude, heat stability, hemolytic activity, complement fixation, effect of serum diluent and cell suspending medium on antibody titer, and the ability of the antibody to sensitize cells for the anti-globulin test. The in-vitro behavior of dog isoantibodies is correlated with a variety of in-vivo reactions.
Studies on the Use of Enzyme-Treated Red Cells in Tests for Rh Sensitization
Authors: Wiener Alexander S. , Katz Lillian
Published: January 2023

The use of enzyme-treated red cells is a sensitive and specific method for testing for Rh-Hr antibodies and antibodies of other specificities. The most satisfactory results have so far been obtained with trypsin, papain, and ficin. For best results red cells should be washed three times with saline solution before treating them with enzyme, in order to remove the enzyme inhibitor present in normal human plasma. The sensitivity of the reactions increases with the period of incubation of the red cells with the enzyme preparation. Most satisfactory results were obtained by incubating the cells with the enzyme for a period of one hour at body temperature. Prolonged treatment with the enzyme may give rise to non-specific clumping. The action of the enzyme can be stopped at any time by washing the cells with saline in order to remove the enzyme. Chilling slows or stops the action of the enzyme, but this can be started again by rewarming the mixture. The use of enzyme-treated cells gives more sensitive results in tests for Rh sensitization than other standard tests hitherto introduced, and equals them in specificity. For example, the titers obtained in general are, on the average, four to five times as high as by the albumin-plasma conglutination technique. In no case of Rh sensitization encountered by us to date has the test with enzyme-treated cells failed to demonstrate the presence of Rh antibodies, although in several of these cases the other tests were negative. The use of trypsinated cells is a sensitive method of demonstrating autosensitization. Autosensitization, as detected in this manner, may be present without producing clinical symptoms. Normal human serum is approximately ⅛ as active as a 1 per cent solution of crystallized soy bean inhibitor in preventing the action of trypsin on red cells. Trypsin inhibitor is present in umbilical cord serum in approximately the same concentration as in adult serum, and is also present in equal concentration in the serum of sensitized Rh-negative individuals. Normal human serum inhibits the action of papain, whereas soy bean inhibitor, which is a more potent trypsin inhibitor, has no effect on papain. Thus the action of the inhibitors is specific. Evidence is produced to show that the enzymes do not damage any of the hemagglutinogen loci, but act instead upon a substance, probably a serum protein, which is intimately bound into the surface of the red cells. The clumping which results when enzyme-treated cells are coated with antibody appears to be related to conglutination rather than agglutination. Diagrammatic representations of these concepts are offered.
A Study of the Reaction between Human Serum Albumin and its Homologous Equine Antibody through the Medium of Light Scattering
Authors: Gitlin David , Edelhoch Harold
Published: January 2023

The reaction between bovine serum albumin and homologous equine antibody has been studied by light scattering measurements. Equilibrium is reached more rapidly in the zone of antigen excess than in the zone of antibody excess. The final light scattering values obtained for definite antigen/antibody ratios appear to be the same in the equivalence zone when the final state is approached from either zone of excess, whether one reagent is added to the other all at once, or whether it is added in several successive increments. On the other hand, the reaction on the antigen excess side of the precipitation curve is rapidly and completely reversed by addition of excess antigen, while in the antibody excess zone, additional antibody results in only a very slow reduction in the amount of scattered light at 90° to the incident beam. However reversal is indicated under these conditions also if scattering is measured at angles closer to the incident beam. Large complexes consisting of soluble aggregates of antigen and antibody appear to exist over all possible ratios of antigen to antibody. Specific aggregates are larger in size the closer the reaction takes place to the point of maximum precipitation.
Nontoxic Influenza Virus
Authors: McKee Albert P.
Published: January 2023

The production of nontoxic influenza A virus has been described. This was accomplished by inoculating undiluted, non-mouse-adapted, allantoic fluid virus into the allantoic sac of the developing chick embryo. Mouse-adapted influenza virus would not cause nontoxic virus to be produced. Exactly why the virus grows as a nontoxic suspension is not understood. The virus particle, however, appears to be responsible in part, although a soluble factor has not been excluded. The nontoxic virus appears to be as good an antigen as the toxic. Although most of the attempts to produce nontoxic virus meet with success some failures are encountered. Some of the problems for further study have been set forth.
Tuberculin Type Sensitivity to Spinal Cord Antigen in Rabbits with Isoallergic Encephalomyelitis
Authors: Waksman Byron H. , Morrison L. Raymond
Published: January 2023

In rabbits with experimental isoallergic encephalomyelitis, intracutaneous tests with homologous spinal cord suspended in saline gave reactions having the gross and histologic characteristics of the tuberculin response. Skin reactivity could not be passively transferred with large amounts of serum. The development of skin reactivity was correlated with the development of experimental disease, both in degree and in time. Positive corneal reactivity could be demonstrated in approximately one half to one third of the animals developing encephalomyelitis, especially in those surviving longer than 2 weeks. Titration of inoculation dose and skin test dose was carried out. Skin reactivity remained low and encephalomyelitis failed to appear in animals inoculated with low doses of antigen or tubercle bacilli, in animals inoculated subcutaneously or intraperitoneally, in immature animals, and in animals with cachexia. By using the skin testing method as a means of comparing nervous tissue fractions, antigenic effectiveness was found in a residue insoluble in water and ether and not affected by freezing and thawing in the presence of ether. Proteolipid A of beef brain also gave positive reactions. Encephalomyelitis could not be produced by the water soluble, dialyzable fraction described by Hottle et al. This substance was likewise not effective in skin tests. Dicumarol dosage, sufficient to keep the prothrombin level below 50% of normal, had no effect on incidence of experimental disease.
Studies on the Prevention of Mumps
Authors: Henle Gertrude , Henle Werner , Burgoon Jane S. , Bashe Winslow J. , Stokes Joseph
Published: January 2023

The results of over 1800 skin tests and over 1500 complement fixation tests have been analyzed in terms of past mumps infection, age of the individual and geographical area.

Correlation between past known infection and positive complement fixation or skin tests was of the order of 70 to 80%. With the skin test it was somewhat higher in the adult than in individuals less than 18 years of age, whereas the reverse was noted with the complement fixation test.

Neither a positive complement fixation reaction nor a positive skin response affords absolute assurance of resistance to mumps but the incidence of infection among such individuals was found to be less than 2%, whereas it was many times that in those giving negative reactions. Since discrepancies between the results of the 2 tests, when performed simultaneously, were not infrequent, it is obvious that both technics should be employed to attain maximal accuracy in determining the immune status of an individual.
Experimental Human Salmonellosis
Authors: McCullough Norman B. , Eisele C. Wesley
Published: January 2023

Immunity after experimental human infections due to Salmonella meleagridis and S. ana um was studied by challenging the subjects at various intervals and dose levels. Some increased resistance was found in all twenty-three subjects studied although the degree varied considerably.

On the first refeeding using somewhat larger doses of the same strains, sixteen of the twenty-three subjects did not become ill. Of seventeen subjects refed a second time using considerably larger doses, seven again did not become ill. The great majority of illnesses produced by first or second refeeding were milder than the initial illnesses. An increased resistance was present in some instances as long as nine months after the initial attack.

Seven men who developed prolonged carrier states in the initial experiments, with one exception, ceased excreting the organism promptly in the refeeding experiments.
Experimental Streptococcal Pneumonia
Authors: Weinstein Louis , Colburn Charles G. , Seltser Raymond , Mallory G. Kenneth
Published: January 2023

Sulfonamide and penicillin have been found to be without effect on the development of the characteristic cellular reactions in pneumococcal infections in experimental animals. Wood and Irons (1), in a study of pneumonitis resulting from the intratracheal injection of the Pneumococcus in rats, found that the administration of a sulfonamide had no influence on the character of the anatomic changes in the lungs; this was thought to be due to the fact that the drug produced only bacteriostasis and, therefore, the same defense mechanisms were called into play as are present in the absence of chemotherapy. Penicillin, on the other hand, might be expected to alter the tissue responses of the host infected with pneumococci because of its bactericidal activity against this organism. Skinsnes (2), however, has presented evidence indicating that, in spite of the rapid cessation of spread of pneumococci and their early eradication by phagocytic cells following the use of penicillin, the cellular responses in treated and untreated animals were essentially similar.
The Resistance of Mice to Myositis and Central Nervous System Infection Following Immunization with GDVII Mouse Encephalomyelitis Virus
Authors: Rustigian Robert , Pappenheimer Alwin M. , Leblanc Thelma
Published: January 2023

Following immunization of mice by the intraperitoneal route with active GDVII mouse encaphalomyelitis virus, a marked resistance to myositis and local virus multiplication was obtained against subsequent intramuscular challenge of a standard dose of GDVII virus. In addition, there was no invasion of the central nervous system as evidenced by the absence of signs of disease and histologic changes, and the failure to recover active virus from the spinal cords and brains of mice so challenged. Direct intracerebral challenge of a limited number of mice indicated that an immunity was also established in the central nervous system. However, since small amounts of virus were recovered from the central nervous system tissues of some of the immunized mice at the time of challenge, the occurrence of interference cannot be excluded. Immunization by the subcutaneous and intraperitoneal route also led to the development of complement fixing and neutralizing antibodies in considerable concentrations.
On the Stability of Desiccated Snake Venoms
Authors: Schöttler W. H. A.
Published: January 2023

The toxic potencies of desiccated snake venoms were tested over a period of up to 13 years.

It was found that the non-hemorrhagic, so-called neurotoxic venoms had lost little or nothing of their original toxicity in 8 to 9 years of storage in cork stoppered glass tubes in the dark. Hemorrhagic venoms kept under the same conditions had lost 41 to 56% of their power in 9 years and 84% in 13 years (Vipera) and 78 (Bitis) and only 14 (Agkistrodon)% in 8 years. When stored in a frequently opened and re-evacuated desiccator, Agkistrodon venoms lost approximately 70% of activity within one year. Under similar conditions, lyophilized neurotoxic Crotalus venom lost about one third of its original toxic potency in a couple of months whereas its antibody-binding capacity decreased less markedly, if at all.

The significance of these observations is discussed.
Studies of Herpes Simplex Virus in Newborn Mice
Authors: Kilbourne Edwin D. , Horsfall Frank L.
Published: January 2023

Infection of the newborn (1 day old) Swiss mouse with the virus of herpes simplex results in rapidly progressive disease culminating in death within 3–5 days. This lethal disease provides an unequivocal end point for titrations of virus and antibody. With a constant amount of virus the serum dilution end point in neutralization tests is readily reproducible. The newborn mouse is at least as effective as the rabbit or the chick embryo for the recovery of herpes virus from human sources, and possesses the advantage of indicating the presence of virus on initial passage. Susceptibility of the mouse to inoculation of herpes simplex virus by either the intraperitoneal or intracerebral route decreases with age. Antigenic analysis of 3 herpes simplex virus strains failed to show evidence of antigenic difference.
Increase in Virulence of the Lansing Strain of Poliomyelitis Virus with Passage in Mice
Authors: Ainslie John D.
Published: January 2023

Summary and Conclusions

There was a progressive increase in the titer of the line of the Lansing strain of poliomyelitis virus maintained in this laboratory between the 52nd and 84th consecutive passages in mice, from 10−2.5 to 10−4.6. The greatest single increase between pools was 5-fold, and occurred after the 71st passage. The daily morbidity data, and the number of days before 50% of the mice were paralyzed demonstrate that with increasing numbers of passages there was a progressive shift toward earlier involvement.

There were no detectable immunologic differences between the line of the Lansing strain of poliomyelitis virus maintained in this laboratory and that maintained in another laboratory through approximately 200 passages in mice and 3 recent passages in monkeys. The line maintained in this laboratory was apparently unrelated to, and consequently not contaminated with, 2 strains of virus isolated from normal stock mice which developed spontaneous paralysis during the course of these experiments.
Studies on Vaccinia Virus
Authors: Briody B. A. , Ledinko Nada , Stannard Claudia
Published: January 2023

A labile principle capable of neutralizing the egg infectivity of vaccinia virus is present in normal guinea pig serum. This “non-specific” inhibitor is inactive against vaccinia hemagglutinin. It can be stored at −60 C with no loss of activity, but rapidly deteriorates when stored for a few hours at 4 C. It is inactivated by heating to 56 C for 30 minutes. Removal of the hemolytic activity of complement from the GP serum does not appreciably reduce the activity of the viral inhibitor. A similar component capable of neutralizing vaccinia virus is not present in detectable amounts in the serum of mice. The pattern of infection following intranasal inoculation of vaccinia virus in the GP differs appreciably from that in the mouse.
in Vivo and in Vitro Studies of Serological Specificity among Viruses of the Psittacosis-Lymphogranuloma Venereum Group
Authors: Hilleman M. R. , Haig D. A. , Helmold R. J.
Published: January 2023

The serological specificity of the direct and indirect complement-fixation, serum neutralization, conglutinating complement absorption (C.C.A.T.), and hemagglutination-inhibition tests for viruses of the psittacosis-lymphogranuloma venereum group was compared in tests with rooster, human, rabbit and pigeon sera. Purified elementary body, purified lipid, hemagglutinating (meningopneumonitis) and phenol-enhanced antigens prepared from psittacosis, ornithosis (including meningopneumonitis), LV, feline pneumonitis and mouse pneumonitis viruses were used.

The rooster antisera were group-specific in the indirect complement-fixation test. This was in contrast to the sharp specificity which these same sera showed in serum neutralization tests.

The hemagglutination-inhibition tests with rooster and pigeon sera and the conglutinating complement absorption tests with human, rabbit and pigeon sera all gave group-specific reactions. Group-specificity was likewise shown in the direct complement-fixation tests with human, pigeon and rabbit sera when phenol-enhanced and lipid antigens were used. Minor antigenic differences, however, were evident when the rabbit and certain of the pigeon sera were tested with purified elementary body antigens. These differences were neither sufficiently consistent nor great enough to be of practical value in differentiating the viruses of the group.
The Cellular Transfer in Humans of Delayed Cutaneous Reactivity to Hemolytic Streptococci
Authors: Lawrence H. Sherwood
Published: January 2023

In a series of 472 adult patients without apparent streptococcal disease or its complications, the incidence of positive delayed cutaneous reactions was as follows: To intact Streptococcal cells—39% of 67 patients. To SK-SD—69% of 112 patients. To M Substance—36% of 293 patients. Of the total 472 patients, the overall incidence of positive reactions to the streptococcal materials was 45%. It has been possible to transfer passively, in 14 consecutive instances, generalized cutaneous streptococcal reactivity of the delayed tuberculin type to streptococcus-negative human recipients by means of viable leucocytes obtained from streptococcus-positive human donors. This was accomplished with intact streptococcal cells as the test material in 4 instances, with SK-SD as the test material in 6 instances, and with M Substance as the test material in 3 instances. In one instance it was possible to induce delayed cutaneous reactions to intact streptococcal cells, SK-SD and M Substance simultaneously in the same negative recipient. Delayed cutaneous reactions did not develop in the streptococcus-negative recipient when the transferred leucocytes were obtained from streptococcus-negative donors. The endowment of the negative recipient with the capacity to develop generalized delayed cutaneous reactivity to streptococcal materials, following leucocytic transfer, is a transient phenomenon. The results of leucocytic transfer of delayed cutaneous reactivity to hemolytic streptococcal materials in humans generally appear to parallel those reported in humans using tuberculin as the test substance.
A Study of Infections Caused by Mumps and Newcastle Disease Viruses. I. Specific and Non-Specific Serologic Relations
Authors: Wenner Herbert A. , Jenson Marian H. , Monley Anne
Published: January 2023

Specific antibodies, measured by the methods of hemagglutination-inhibition and complement-fixation, appeared in serum following experimental infection of monkeys with mumps and ND viruses. It could not be demonstrated, using the two serologic methods, that these viruses shared a common antigen. The hyperimmunization of rhesus monkeys with mumps and ND viruses did not provide convincing evidence of a serologic relationship between these viruses. Complement-fixing antibodies for NDV may appear in serums obtained from some human beings recently convalescent from mumps parotitis. Hemagglutination-inhibitor substance(s) was present in many serums at the onset of mumps; although a rise in titer occurred, the order of increase was not enough to warrant a conclusion that mumps and ND viruses shared similar antigenic components. A non-specific substance(s) has been found in many serums obtained from human beings and rhesus monkeys which inhibits hemagglutination of fowl RBC, and in some, apparently, fixes complement in the presence of mumps and ND viruses. The non-specific serum-inhibitor is discussed in regard to the apparent, but false, serologic relations of mumps and ND viruses.
The Growth of Mouse Encephalomyelitis Virus (Theiler's Fa Strain) in Embryonated Eggs
Authors: Lawson Robert B.
Published: January 2023

Theiler's FA mouse encephalomeylitis virus grows equally well when suspensions of infected mouse brain are inoculated into embryonated chicken eggs by either the intra-embryonic or chorio-allantoic membrane routes. The optimal temperature of incubation after inoculation is 34–36 C. Lower temperatures result in low embryo survivals and irregular growth of virus, and at higher temperatures satisfactory growth is only occasionally obtained. There is little difference in virus growth whether embryos are inoculated after six or eight days of preliminary incubation. When inoculated by a peripheral route, virus growth in the embryo starts building up by the fourth to the fifth days after inoculation and reaches a peak by the eighth to tenth days after inoculation. The highest titres of virus will be found in the embryo, irrespective of the relative amounts of nervous tissue. The embryonic membranes contain the next largest amounts of virus, and the fluids the least amount. The concentration of virus in the inoculum has little effect on subsequent infectivity titres. One fundamental difference was noted in the behavior of FA virus from infected mouse brains and virus from infected embryonic products. Whereas original mouse brain virus would not propagate when inoculated into the yolk sac, egg adapted virus grew as well or better when inoculated by the yolk sac route as by the embryonic or chorio-allantoic membrane routes.
Parallel Studies of Complement and Blood Coagulation
Authors: Rice Christine E. , Boulanger Paul , Plummer P. J. G. , Annau E.
Published: January 2023

The repeated oral or parenteral administration of ethionine produced in female guinea pigs a fatty degeneration of the liver of varying extent and severity; some animals also showed pancreatic changes involving the acinar cells. Fatty infiltration was observed in the livers of some of the male guinea pigs injected with ethionine but it tended to be less extensive than in females similarly treated. Both male and female guinea pigs showed a pronounced drop in complement titer; of the four major components, C′1, C′2 and C′3 were most affected, although a decline in C′4 also occurred. A moderate to marked prolongation of the coagulation time of the plasma was recorded in guinea pigs that had received repeated doses of ethionine. Accelerator-globulin (labile factor) as well as prothrombin and fibrinogen appeared abnormally low in many of the specimens. The sera of many of the ethionine-treated guinea pigs, even though normal in total protein content, had abnormally high albumin-globulin ratios owing to a marked decrease in globulin. Although a general relationship has been demonstrated between the fall in complement titer, the degree of liver damage and the shift in serum protein pattern, changes in complement activity were often detected before these other effects of ethionine-treatment had become evident.
Differences in the Capacity of Human Serums to Neutralize Herpes Simplex Virus
Authors: Rose Harry M.
Published: January 2023

Two types of neuralization tests were performed simultaneously on human serums known to contain antibody to herpes simplex virus. Significant variations in neutralizing capacity were not observed when constant amounts of the undiluted serums were tested against single or multiple concentrations of virus, but fairly wide differences were readily detected when dilutions of the serums were tested against a constant amount of virus. The cutaneous reaction to herpes viral antigen was negative in several patients, all of whom had relatively low titers of antibody in their serums. The significance of these findings is discussed.
Immunological Studies of Egg White Proteins
Authors: Wetter L. R. , Cohn M. , Deutsch H. F.
Published: January 2023

It has been possible to resolve a portion of the curve describing the precipitin reaction between egg white and anti-egg white rabbit serum as the sum of the individual reactions between purified ovalbumin, conalbumin, lysozyme and ovomucoid with their corresponding antibodies in anti-egg white serum. The four proteins studied comprise approximately 92% of egg white protein, yet an unexpectedly small proportion of the total antibody in anti-egg white serum is directed against them. Most of the antibody response is to minor and as yet poorly defined antigenic components of egg white.
Quantitative Studies on the Antigen-Antibody Reaction by the Monolayer Technique
Authors: Ogata Tomio , Tachibana Taro , Suzuki Kan , Fukuda Kiyoshige , Yamaoka Seizaburo
Published: January 2023

By the monolayer technique the relationship between the number of haptenic groups in azoproteins and the number of antibody molelules combined was quantitatively observed. The optical thickness of the antibody layer specifically attached to a monolayer film of atoxyl-azo-ovalbumin increases in linear relation to the increase in the number of haptenic atoxyl groups, until it reaches a “saturation” point with an antigen containing about 30 haptenic groups, and thereafter the thickness remains unchanged, even if the number of determinant groups is increased over 30. Quantitative observations were made with monolayer films of mixtures of azoprotein (containing a certain number of haptenic groups) and native ovalbumin in various proportions. The thickness of the antibody layer decreased proportionally with the decrease in the average number of haptenic groups per unit area in the mixture films (hetero-monolayers), approximately corresponding to the thickness of the antibody layer obtained with homogeneous film (homomonolayer) containing the same number of haptenic groups per molecule. In multilayer films the thickness of the antibody layer increased proportionally with the number of layers each containing the same number of haptenic groups. The ratio of increase in the thickness of the antibody layer is in complete accord with that in the case of a single monolayer experiment. From the experimental results described in this paper the significance of the thickness of the antibody layer in a monolayer technique was made clear in that it indicates the average density of antibodies adsorbed on an antigen monolayer film. The structural arrangements of the haptenic groups in the monolayer film and of the antibodies on the antigen film were discussed in terms of molecular orientation.
Hemolysis with Complement of Intact Azo-Erythrocytes Sensitized with Antisera Homologous to the Attached Azo-Grouping
Authors: Silverstein Arthur M. , Maltaner Frank
Published: January 2023

The data presented extend the observations of other investigators on the ability to obtain immune hemolysis with complement of erythrocytes sensitized with antibodies other than the anti-erythrocyte antibody. It has been shown that sheep erythrocytes, to which p-azo-phenyl-arsonate groupings have been attached, may be hemolyzed upon addition of complement to the cells previously sensitized with rabbit anti-p-azo-phenyl-arsonate antibody.
Serologic and Dermal Reactions in Guinea Pigs Injected Intradermally with Brucella Antigens
Authors: Carpenter Charles M. , Boak Ruth A. , DeBoer Carl J.
Published: January 2023

Dermal sensitivity was not induced in guinea pigs by repeated intradermal injections of brucellergen, brucellin, or a Brucella vaccine containing 200,000,000 dead cells per ml. Repeated intraperitoneal injections of guinea pigs with brucellergen or brucellin failed to stimulate a significant production of either agglutinins or complement fixing antibodies. Brucella vaccine, however, prepared from dead cells was antigenic when administered intraperitoneally and caused significant antibody formation. The quantity of each agent required to cause production of serum antibody is many fold the amount used in successive intradermal tests. The order of increasing antigenicity of the Brucella preparations tested was: brucellergen, brucellin, and Brucella vaccine. The data obtained from guinea pigs indicate that repeated intradermal tests with brucellergen will not sensitize patients to protein nucleates derived from Brucella.
Interaction of Protein Antigens and Antibodies
Authors: Kleinschmidt W. J. , Boyer P. D.
Published: January 2023

Experiments on the solubilization and dissociation of egg albumin-anti-egg albumin precipitates have been conducted with acid, alkali, salts, dodecyl sulfate, and urea and with combinations of these substances.

Alkaline buffers of pH 11.0 and higher at 2 C dissolved the egg albumin-anti-egg albumin precipitate. Electrophoretic examination of dissolved precipitates showed no dissociation of the precipitate at pH 11.15, approximately 17% dissociation at pH 11.7, and 100% dissociation at pH 12.3. Tests with egg albumin and isolated rabbit immune γ-globulin revealed that the immune γ-globulin was altered only slightly at pH 11.7 but that marked changes occurred at pH 12.3.

A mixture of 0.3 M KCNS and 2 M urea at pH 10.75 produced complete dissolution of egg albumin-anti-egg albumin precipitates: however, electrophoretic analysis revealed only approximately 5% dissociation under these conditions. Increase in the pH of the mixture resulted in changes in the egg albumin and immune γ-globulin as measured by survival tests.

Egg albumin-anti-egg albumin precipitates dissolved completely in acid buffers at pH 3.4 or lower. Electrophoretic evaluation of possible dissociation at pH 2.8–3.2 was not feasible because of the similar mobilities of the components in this pH range. Exposure of immune γ-globulin at pH 3.4 or less produced changes as evidenced by complex formation leading to increased precipitate formation following egg albumin addition.

The dependence of dissociation of egg albumin-anti-egg albumin precipitates upon conditions sufficiently drastic to cause changes in the antibody component of the precipitates when tested separately suggest that the forces responsible for the primary interaction of egg albumin and anti-egg albumin are of the same nature and magnitude as those responsible for maintaining the native configuration of the γ-globulin.
Effect of Multiple Injections of Antigen upon the Specificity of Antisera
Authors: Leone Charles A.
Published: January 2023

Rabbits were injected with small amounts of the hemocyanins of Crustacea for four or five short series. Three animals were presensitized with antigen, and then given several series of injections after a period of rest of thirty days. The change in the content of antibody, and the change in the specificity of the antisera were observed after each series by means of a photoelectric, turbidimetric titration of the entire range of reaction between antigen and antibody. The amount of antibody in the antisera generally increases following each series of injections. However, decreases have been observed to occur following the third and fourth series. The specificity of antisera generally decreased during the course of immunization. However, increases in specificity following previous decreases in specificity also occurred. Presensitization seems to be equivalent to one or two series of injections in so far as the specificities of antisera are concerned. Relatively large dilutions of immune sera which are in the “maximal antibody-constant specificity” state do not increase their specificity. The specificity of an antiserum is primarily dependent upon the physiological state of the animal which produces it. Under uniform schedules of injection the specificities of antisera produced against the same antigen will vary from animal to animal. Thus, the specificity of an antiserum is not necessarily correlated with the amount of antigen involved in the immunization. The specific characteristics of the antigens, which are being compared, help to determine the specificity which is ascribed to an antiserum.
Comparison of the Antigenic Patterns of Influenza a Virus Strains Determined by in Ovo Neutralization and Hemagglutination-Inhibition
Authors: Hilleman Maurice R. , Horsfall Frank L.
Published: January 2023

The ratio between the homologous in ovo neutralization and hemagglutination-inhibition titers of rooster antisera against influenza A virus strains varies widely. The hemagglutination-inhibition technique yields, in cross-serological experiments, somewhat less evidence of an antigenic difference between strains than does the in ovo neutralization procedure. Analysis of the antigenic relation between 2 strains by means of antiserum against 1 of the strains (r value analysis) may yield very misleading results, particularly if the hemagglutination-inhibition procedure is employed. Similar analysis by means of antisera against both strains (R value analysis) shows good correlation between the results obtained by hemagglutination-inhibition and by in ovo neutralization.

The results of complete cross-serological experiments carried out both by the in vivo and the in vitro procedures indicate that influenza A virus strains may show alteration in antigenic composition during successive annual epidemics. They indicate, also, that there is little evidence of antigenic difference between strains recovered in various parts of the world during 1951.
Immunochemical Studies on Tobacco Mosaic Virus
Authors: Malkiel Saul
Published: January 2023

No appreciable difference was seen in the serological reaction between native tobacco mosaic virus and acetyl, p-chlorobenzoyl, carbobenzoxy, reduced carbobenzoxy, acetylglycine-treated, and benzal derivatives of the virus when tested with antiserum to the native virus.

Tobacco mosaic virus-azo-arsanilic acid produced no specific haptenic antibody in the rabbit when used as an antigen. The modified virus did react with an antiserum to a heterologous azo-arsanilic acid derivative.
The Role of Tubercle Bacilli in Adjuvant Emulsions on Antibody Production to Egg Albumin
Authors: Fischel Edward E. , Kabat Elvin A. , Stoerk Herbert C. , Bezer Ada E.
Published: January 2023

Guinea pigs injected with crystalline egg albumin in an emulsion with the Freund adjuvants and containing killed tubercle bacilli showed substantially increased and prolonged antibody levels in their serum measured by the quantitative precipitin reaction as compared with guinea pigs injected with a similar emulsion lacking killed tubercle bacilli. The increased antibody formation was correlated with local granuloma formation and hyperplasia in the regional lymph nodes and spleens of animals receiving the emulsion containing killed tubercle bacilli.
General Preface to Studies on the Cultivation of Poliomyelitis Viruses in Tissue Culture
Authors: Enders John F.
Published: January 2023

These remarks are designed as a preface to a series of reports on the propagation of the viruses of poliomyelitis in tissue culture. To achieve clarity in presentation, the division of topics has been somewhat arbitrary. In consequence each report will contain data obtained through the application of phenomena or techniques described in certain of the other papers. Accordingly, it was thought that it might prove helpful to the reader to summarize here the content of the various papers and to indicate their principal interrelationships. It also seemed appropriate to review in a preface of this sort the literature relevant to the series as a whole as well as the earlier communications from this laboratory.

Since the demonstration by Landsteiner (1) in 1908 that poliomyelitis could be produced in monkeys, various workers have attempted to cultivate the causative agent in vitro.
On the Photolability of Serum Complement
Authors: Lundberg E. G.
Published: January 2023

There has been shown by these experiments that: The light-destruction may be fairly well expressed by the monomolecular formula.The rate of the destruction is low, k varying from 0.019 to 0.050.The temperature-influence is small or none. μ certainly does not exceed two or three thousandths—which signifies an increase in k of 1.1 to 1.7 per cent for 1°C. increase of temperature at 27°C.Variation in lamp-distance causes changes in reaction-speed, which do not differ essentially from inverse proportionality to the light-intensity.Dilution of serum before radiating causes not only the expected decrease of complement strength, but also alters very irregularly its magnitude. It causes, too, an increase in reaction-speed, which, however, is not parallel to the dilution-amount.The color of serum changes obviously during radiation, from orange to dull yellow, the opalescence increasing at the same time. This is accounted for in the colorimetry.As regards the exactness of the measurements made with this method, the primary figures have a possible error of about ± 10 per cent. The graphically found values may be regarded as more exact (about 5 per cent possible error). The k- values are chiefly found to differ within ± 12 per cent from the mean, which may be regarded as quite satisfactory. The temperature-variation in each experiment—being within ± 0.4°—may be disregarded in consequence of the insignificant temperature-influence.
Studies on the Toxicity of Human Blood Plasma for Guinea-Pigs
Authors: Levinson S. A.
Published: January 2023

Blood plasma obtained from pregnant women is more toxic for the guinea-pig on intravenous injection than plasma obtained from normal individuals. Human placental plasma is practically nontoxic. Similar relations are found with dog plasma obtained from pregnant dogs and from full term fetuses.

Plasma obtained during the menstrual cycle (before and after) is occasionally more toxic for guinea-pigs than normal female plasma.

The cause of death in the guinea-pig is an intravascular clotting of the capillaries of the lungs, with a resulting asphyxia, and occlusion in other capillaries as well (brain, liver, etc.). Death can be prevented if the animal is hirudinized, or if the amount of citrate simultaneously injected, is increased.