bluuebunny/crossref_metadata_2025 huggingface dataset:
STRAIN-SPECIFIC ELEMENTS IN INFLUENZA ANTIGENS
Authors: Hirst George K.
Published: June 2004

Rabbit antisera were prepared against ten antigenically different influenza A strains. These sera were absorbed with one or more heterologous strains and in each case all the heterologous or crossing antibody was removed; the anti-bodies remaining after this treatment were specific for the immunizing strain or group of strains.

On the basis of reactions with absorbed sera, the strains fell into seven groups.

Absorbed specific antisera of these groups were used to test the HI titer against a large number of influenza A viruses. Most of the strains were inhibited by a single serum, a few were inhibited by none of the sera, and only one strain was inhibited by two antisera.

The grouping of strains by this method was less equivocal than classifications based on previous tests. When more fully developed, this technique promises to be of interest and assistance in the study of influenza, especially from the epidemiological and prophylactic standpoints.
STUDIES ON THE GENERALIZED SHWARTZMAN REACTION
Authors: Good Robert A. , Thomas Lewis
Published: June 2004

Intravenous injection of thorotrast or trypan blue rendered rabbits susceptible to the production of bilateral cortical necrosis of the kidneys by a single intravenous injection of small amounts of meningococcal or Serratia marcescens toxin. This reaction was not produced when thorotrast or trypan blue were injected after toxin had been given.

A single intradermal injection of toxin produced hemorrhagic skin lesions resembling the local Shwartzman reaction in rabbits given thorotrast 6 hours previously. These animals also developed bilateral cortical necrosis of the kidneys. When the order of injection was reversed, and thorotrast given after toxin, neither skin nor kidney lesions occurred.

The skin and kidney lesions in thorotrast-treated rabbits were, like the local and generalized Shwartzman reactions, completely prevented by treatment with nitrogen mustard, in doses sufficient to produce polymorphonuclear leukopenia.

The significance of these reactions, and their relationship to the previously described response to toxin in cortisone-treated rabbits, are discussed.
FATE OF MUMPS VIRUS IN THE EMBRYONATED EGG AS DETERMINED BY SPECIFIC STAINING WITH FLUORESCEIN-LABELLED IMMUNE SERUM
Authors: Watson Barbara K.
Published: June 2004

Specific staining with fluorescein-labelled immune serum was used to study the progress of mumps virus infection in a series of embryos harvested at daily intervals. The results were compared with the hemagglutinin and infectivity titers of the corresponding extraembryonic fluids. The evidence obtained indicated that the multiplication of the virus was restricted to those cells which came into surface contact with infected fluid. Following intraamniotic inoculation into 8 day old embryos, these included the cells lining the amniotic membrane and the epidermal and pharyngeal epithelium. Depending apparently on the extent of the contamination of the allantoic cavity and of the extraembryonic celom in the course of inoculation, varying amounts of virus were also present in the cells lining the chorioallantoic membrane and occasionally in the peritoneum. During the later stages of the infection, staining which was principally if not entirely extracellular was seen in the gastrointestinal tract, and, after the dissolution of the tracheal plug, in the respiratory tract.

The virus was first detected 1 to 2 days after inoculation as brightly fluorescent intracytoplasmic granules of varying size. As these granules increased in size and number they gradually filled the cytoplasm of the outer one or two layers of cells lining the adjoining cavity. The extent and brightness of the staining reached a peak 4 to 6 days after inoculation and thereafter decreased progressively.

The staining of the tissues closely paralleled the rise and fall in the infectivity of the extraembryonic fluids. The development of hemagglutinins, on the other hand, provided a less sensitive measure of virus multiplication than did the staining.

No differences were detected in the mortality of the infected and control series of embryos nor was there evidence of any pathological changes.

In contrast to the 8 day old embryos, no virus multiplication was detected following the inoculation of 16 day old embryos.
THE MECHANISM RESPONSIBLE FOR THE HYPERCHOLESTEREMIA INDUCED BY TRITON WR-1339
Authors: Friedman Meyer , Byers Sanford O.
Published: June 2004

Injection of triton WR-1339 into rats leads to a rapid increase in the cholesterol, cholate, and various lipid fractions of their blood. The increase in cholesterol is confined to the blood itself.

The cholesteremic effect of triton was not dependent upon a prior accumulation of cholate in plasma.

The liver was found to be the source of the excess cholesterol but the rate of cholesterol synthesis, the excretion of cholate, and the cholesterol content of the liver were not changed by injection of triton.

The cholesteremic effect of triton is not due to alteration in the intestinal excretion of cholesterol.

Transfer of blood between "tritonized" and normal rats leads to a disappearance of the hypercholesteremia in the former and its appearance in the latter animals.

The plasma proteins of rats injected with triton are markedly changed qualitatively.

Heparin was found to inhibit the hypercholesteremic effect of triton.

The hypercholesteremia following triton injection appears to be due to a fundamental physicochemical change in the plasma proteins produced by injection of this detergent.
THE EFFECT OF X-RADIATION ON THE OXYGEN UPTAKE OF EMBRYONATE EGGS
Authors: Greiff Donald , Blumenthal Herman T. , Chiga Masahiro , Pinkerton Henry
Published: June 2004

Groups of 10 day old embryonate eggs were given 250, 500, 750, and 1000 r of x-radiation, and oxygen consumption determinations were made subsequently at various intervals during a period of 90 hours. In general, the effect of radiation was moderately stimulatory, but after 90 hours the respiratory rates of the 250 and 1000 r groups were well below those of the control groups. The most striking effect, noted in 3 separate experiments, was the occurrence of a "3 step staircase" type of oxygen consumption curve in all irradiated groups, the levelling off periods apparently occurring between the 4th and 14th, the 24th and 36th, and the 42nd and 66th hours after exposure. These curves were in striking contrast to those shown by groups of non-irradiated eggs, which were practically of the straight line type.
THE EFFECT OF X-RADIATION ON THE MULTIPLICATION OF INFLUENZA A VIRUS IN EMBRYONATE EGGS
Authors: Blumenthal Herman T. , Greiff Donald , Chiga Masahiro , Pinkerton Henry
Published: June 2004

Groups of embryonate eggs were given 250, 500, 750, and 1000 r of x-radiation. 18 hours later, these 4 groups, together with a control group, were injected intra-allantoically with influenza A virus. Radiation at all dosage levels caused significant changes in the infectivity titre curves during the next 90 hours. The most striking alterations were the prolonged incubation period and the uniformly low infectivity titre in the group of eggs given 750 r.
STRUCTURAL CHANGES PRODUCED IN BROWN-PEARCE CARCINOMA CELLS BY MEANS OF A SPECIFIC ANTIBODY AND COMPLEMENT
Authors: Kalfayan Bernard , Kidd John G.
Published: June 2004

Structural changes were regularly observed in Brown-Pearce rabbit carcinoma cells that had been brought into contact, in the presence of complement, with rabbit serum containing an antibody that reacts specifically with a distinctive sedimentable constituent of the carcinoma cells. The cellular changes appeared rapidly and were accompanied by an equally rapid loss of viability.

The structural changes, as disclosed by histological and cytological methods, including phase contrast microscopy, were described in detail and illustrated. Essentially they were characterized by the entrance of considerable quantities of fluid into the cell, together with swelling and disorganization of its cytoplasm, vesiculation and rupture of the bulk of its cytoplasmic particles, and rapid and virtually complete loss of cytoplasmic basophilism. The plasma membranes, though stretched thin about the swollen cytoplasm of the altered cells, and otherwise changed also, remained unruptured during many hours' observation. The nuclei of the altered cells, however, remained relatively un-changed, their membranes persisting unruptured and their sap remaining wholly transparent and undiminished in amount for long periods, while within it the chromatin retained its staining properties, though sometimes becoming clumped and marginated; by contrast, the nucleoli of the treated cells promptly shrank and lost much of their affinity for the basic dyes.

The experimental conditions under which the structural changes became manifest were given in detail, together with an analysis of the findings and brief mention of certain of their implications for cytology and immunology.
INDUCTION OF STREPTOMYCIN RESISTANCE IN SENSITIVE HEMOPHILUS INFLUENZAE BY EXTRACTS CONTAINING DESOXYRIBONUCLEIC ACID FROM RESISTANT HEMOPHILUS INFLUENZAE
Authors: Alexander Hattie E. , Leidy Grace
Published: June 2004

Resistance to streptomycin, of a degree exceeding 1000 µg. per ml., has been induced in sensitive strains of Hemophilus influenzae by exposure for 10 minutes to desoxyribonucleic acid-containing extracts isolated from a strain of type b Hemophilus influenzae which had emerged resistant to 1000 µg. of streptomycin per ml. DNA is essential for the process which brings out this change; the reaction can be prevented by destruction of the DNA with crystalline desoxyribonuclease.The resistant trait which is created in this way is heritable.

The nature of the process which induces resistance is similar in all respects to the reaction which induces heritable changes in type specificity of H. influenzae.

These results offer another example of the gene-like action of highly specific DNA's.

The pattern of resistance brought out in a bacterial population exposed to the DNA-containing, resistance-inducing extract, is similar to that which occurs when emergence of resistance of H. influenzae to streptomycin follows the selection by streptomycin of spontaneously occurring resistant mutants. The change in a bacterial cell from average susceptibility to streptomycin to resistance to 1000 µg. of streptomycin per ml. can occur in a single step.
EXPERIMENTAL ERYTHROBLASTOSIS FETALIS IN RABBITS
Authors: Kellner Aaron , Hedal Emily F.
Published: June 2004

Female rabbits became immunized during pregnancy to the rabbit blood group factors G or g in five out of ten instances in which the red cells of the fetuses carried one of the factors absent in the mother. Antibodies so produced were of low titer and disappeared in all cases within 6 weeks after the birth of the litter. Repeated pregnancies did not result in additive increases in titer.

Antibodies to the G-g factors, whether produced by the injection of red cells or by pregnancy, crossed the placenta readily from mother to fetus and were found at birth (and prior to nursing) associated with the red cells and in the serum of the fetuses. The rabbit placenta appeared to be equally permeable to the agglutinating and coating antibodies.

The implications of these findings and their relation to the pathogenesis of erythroblastosis fetalis are briefly touched upon.
STUDIES ON ENTRY AND EGRESS OF POLIOMYELITIC INFECTION
Authors: Faber Harold K. , Silverberg Rosalie J. , Dong Luther
Published: June 2004

Poliomyelitis virus, when ingested by cynomolgus monkeys in their regular food, infected peripheral ganglia (nodose) as early as the 3rd day, as shown by recovery of the virus. Conditions on the 2nd and 4th days were not investigated, but on the 5th and 6th days, virus was recovered from the Gasserian and nodose ganglia, and from the superior cervical sympathetic and celiac ganglia.

The findings indicate that the method of oropharyngeal swabbing used in a study already reported and the method of simple feeding used in the present study produce comparable results.

Viremia, noted in the present study, was contemporaneous with virus recoveries from the ganglia.

Reasons are presented why the peripheral ganglia are the most probable source of viremia since these are the only known site of early lesions (which are typical and appear as early as the 2nd day after oral infection) and no lesions are known to occur in extraneural tissues.

Invasion of the CNS occurred in 3 animals out of 11; one on the 5th and 2 on the 6th day. Whether this was due to viremia or to centripetal extension along axonal channels is not clear.
THE PROTECTION OF INTRACELLULAR BRUCELLA AGAINST THERAPEUTIC AGENTS AND THE BACTERICIDAL ACTION OF SERUM
Authors: Shaffer James M. , Kucera Carrell J. , Spink Wesley W.
Published: June 2004

A method for the in vitro study of intracellular brucella has been described. Exudative leukocytes containing intracellular brucella have been maintained in vitro in a synthetic tissue culture medium or in human or animal serum.

Intracellular brucella are protected in vitro against the lethal action of therapeutic agents or the bactericidal action of serum. This protection of intracellular brucella is dependent upon the presence of an intact, viable host cell.

None of the currently available therapeutic agents, whether used alone or in combinations, were capable of killing all intracellular brucella in vitro in 24 hours. A remarkable protection of intracellular brucella against streptomycin has been demonstrated. The most effective reduction in the number of viable intracellular brucella was accomplished by exposure of the host cells to streptomycin plus aureomycin, terramycin, or chloramphenicol.

The available evidence suggests that the ability of brucella to localize and remain viable within the cells of an infected host is an important biologic factor in establishing and perpetuating brucella infections, despite therapeutic measures or the operation of the host's humoral defense mechanisms.

Reduction of neotetrazolium by leukocytes and brucella in vitro provides a method for assessing the metabolic status of the host cell, but does not discriminate with any degree of certainty a viable from a non-viable intracellular organism.
THE INTRACELLULAR LOCALIZATION OF POLIOMYELITIS VIRUS
Authors: Kaplan Albert S. , Melnick Joseph L.
Published: June 2004

A study was made of the intracellular localization of Type 2 poliomyelitis virus, using the technique of Mirsky and Pollister (23) for cellular fractionation. After isotonic saline homogenization of central nervous system tissue from infected mice, and subsequent centrifugation of the suspension, the virus present in the supernatant fluid was held to be of cytoplasmic origin. Upon serial washings of the sediment with physiological saline, the resulting supernates contained progressively less virus until by the seventh washing, virtually none was present. At this point extraction of the washed sediment with molar NaCl, which lyses the nuclei, yielded substantial amounts of virus, and this was assumed to be from nuclear sources. The possibility has not been excluded however that the "nuclear" sediment was contaminated by cytoplasmic particles too large to remain in the supernate.

Experiments on the increase of virus during the incubation and acute stages of infection have revealed that it was first detectable in the "cytoplasmic" fraction and subsequently in the "nuclear" fraction. Virus in the "nuclear" fraction from paralyzed mice sometimes reached titers almost as high as those found in the "cytoplasm."

Adsorption experiments indicated that the "nuclear" fraction of CNS tissue from normal, uninoculated mice did not adsorb added Type 2 poliomyelitis virus, nor did such fractions adsorb virus procured from the "cytoplasm" or "nuclei" of infected cells.

Although individual mice varied in their response after virus injection, the "cytoplasmic" fraction of paralytic mice was found to contain virus regularly, whereas little more than half of the non-paralytic mice yielded it. When virus was present in the "cytoplasm," it could be found in the "nuclear" fraction of paralytic mice with much greater regularity than in that of non-paralytic mice.

A comparison between the lines of the MEF1 strain of poliomyelitis virus, "adapted" and "non-adapted" to newborn mice, and the Lansing strain, revealed no differences in their intracellular increase. In both infant and adult mice, the chief difference in the findings with non-paralyzed and paralyzed mice lay in the greater concentration of virus in the "nuclear" fractions of the latter group.
THE LOCALIZATION OF HOMOLGOUS PLASMA PROTEINS IN THE TISSUES OF YOUNG HUMAN BEINGS AS DEMONSTRATED WITH FLUORESCENT ANTIBODIES
Authors: Gitlin David , Landing Benjamin H. , Whipple Ann
Published: June 2004

Employing fluorescent antibodies for the detection of homologous plasma proteins in tissue sections, the distribution of plasma albumin, γ-globulin, ß-lipoprotein, ß1-metal-combining globulin, and fibrinogen has been studied in the tissues of infants and children. Plasma albumin, γ-globulin, and ß1-metal-combining globulin were found in many cells and particularly cell nuclei, connective tissues and interstitial spaces, lymphatics, and blood vessels. ß-Lipoprotein was found mostly in the nuclei of all cell types while fibrinogen was restricted largely to the lymphatic and vascular channels, connective tissues and the interstitial spaces.

The widespread distribution of these plasma proteins in cells and connective tissues indicates the magnitude of the extravascular plasma protein pool which is in equilibrium with circulating plasma. Unfortunately, these results do not permit accurate localization of the sites of production of these plasma proteins, but do give some idea of their intimate relationship to the tissues.
THE DEVELOPMENT OF LEISHMANIA DONOVANI IN VITRO AT 37°C
Authors: Trager William
Published: June 2004

Suspensions of leishmanias from the spleen of hamsters infected with Leishmania donovani were placed in culture flasks and incubated at 37°C. In a medium of human erythrocyte extract and human serum there appeared within a day or two aflagellate forms resembling leishmanias but larger, as well as other aflagellate forms more nearly resembling rounded leptomonads. These intermediate forms multiplied during the first 4 days of culture. They then slowly died off, despite frequent renewal of the culture medium. Sometimes a small proportion of motile, typical leptomonads also appeared in such cultures. Leptomonads from cultures maintained at 28°C., when placed in the human red cell extract-human serum medium and incubated at 37°C., survived at least 4 days. For both types of effect, human serum could be replaced by normal hamster serum but not by rabbit serum.

Nicotinamide, added to the human red cell extract-human serum medium at a concentration of 400 mg. per 100 ml., completely prevented the development of intermediate forms from leishmanias and brought about the rapid death of leptomonads at 37°C.
ANTITUBERCULOUS IMMUNITY IN MICE VACCINATED WITH KILLED TUBERCLE BACILLI
Authors: Dubos René J. , Schaefer Werner B. , Pierce Cynthia H.
Published: June 2004

The resistance of white mice to tuberculous infection could be increased by preliminary vaccination with small amounts of tubercle bacilli killed by contact with 2 per cent phenol. Vaccine prepared from a variant strain of human tubercle bacilli unable to multiply in vivo (H37Ra) proved as active as vaccines prepared from either virulent or attenuated strains.

The immunity induced by phenol-killed bacilli persisted for several weeks. Under the conditions of the experiments, however, it was never able to bring about the death of the virulent bacilli used for the challenge infection, even when the infective inoculum was very small. Its protective effect could be detected (a) by the increased survival time of mice infected with a very large dose of virulent bacilli, and particularly (b) by the lower numbers of bacilli present in the organs of mice sacrificed at various periods of time after injection of sublethal infective doses. Under the proper conditions of vaccination the immunity produced in mice by phenol-killed cells of avirulent bacilli was of the same order as that produced by BCG.

The protective antigen proved to be susceptible to heat, particularly at acid reactions. It retained its activity when the bacilli were disintegrated and rendered non-acid-fast by grinding with concentrated phenol. It remained in the insoluble cellular debris when the bacilli were extracted with 88 per cent phenol.

Reasons are presented to support the view that the antigenic components present in the tubercle bacilli (avirulent as well as virulent) killed with phenol play a significant part in several manifestations of increased resistance to tuberculosis.
MULTIPLICATION OF TUBERCLE BACILLI WITHIN MONONUCLEAR PHAGOCYTES IN TISSUE CULTURES DERIVED FROM NORMAL ANIMALS AND ANIMALS VACCINATED WITH BCG
Authors: Suter Emanuel
Published: June 2004

When monocytes derived from normal guinea pigs or rabbits were infected with tubercle bacilli and cultivated in vitro, the bacilli multiplied abundantly within the cytoplasm of these cells.

By contrast, intracellular multiplication of the bacilli was retarded or completely inhibited within the monocytes of rabbits or guinea pigs vaccinated with BCG. This inhibition of growth was observed with both virulent or attenuated strains of tubercle bacilli.

Under the conditions used in the present study, the ability of monocytes to inhibit bacillary proliferation was the same whether serum from a normal animal or from vaccinated animals was used in the tissue culture medium. Moreover, the serum of vaccinated animals did not inhibit multiplication of tubercle bacilli within monocytes derived from a normal animal.

The ability of guinea pig monocytes to interfere with intracellular bacillary proliferation was first perceptible 8 days after vaccination.
ON THE NATURE OF BACTEREMIA IN EXPERIMENTAL PNEUMOCOCCAL PNEUMONIA IN THE DOG
Authors: Robertson O. H. , Hamburger Morton , Gregg Lucien A.
Published: June 2004

In a study of the relationship of natural antipneumococcal immune substances to the incidence and course of bacteremia in dogs with experimental pneumococcus pneumonia the following findings came to light: (1) In non-bacteremic animals, natural immune substances, as measured by the pneumococcidal-promoting action of the serum, continue to be present in relatively undiminished concentration throughout the course of the infection. (2) With the advent of bacteremia these immune properties of the blood tend to decrease or disappear, depending on the degree of bacteremia and the length of the disease course, but in certain instances they persist despite the presence of large numbers of circulating pneumococci. (3) Disappearance of natural immune substances from the blood during bacteremia is followed by their reappearance upon cessation of the bacteremia. (4) Bacteremic blood containing antipneumococcal immune substances and a sufficient quantity of leucocytes is capable of destroying in vitro relatively large numbers of pneumococci and will often sterilize itself. (5) The sequence of bacteremia first, then diminution and disappearance of humoral immunity excludes this antipneumococcal action of the blood as being the principal inhibitor of blood invasion.

These observations have been interpreted as indicating that the bacteremic state consists of a constant escape of pneumococci from the pulmonary lesion and an attempt on the part of the body to compensate for the depletion of circulating immune substances resulting from their progressive immobilization by the pneumococci and their products. Thus, the loss or retention of humoral immune substances in the presence of bacteremia would appear to depend on the rate at which the body can provide new supplies of antibodies and on the number of pneumococci being discharged into the circulation. While the pneumococcidal action of the blood may not be sufficient to prevent the occurrence of bacteremia our study provides ample evidence that it exerts a potent restraining effect on the increase in numbers of pneumococci in the circulation.
SOME ENERGY RELATIONS IN A HOST-VIRUS SYSTEM
Authors: Ackermann W. Wilbur , Johnson R. Bernal ,   With the Technical Assistance of H. Kurtz And L. E. Keith
Published: June 2004

It was found that DNP (2,4-dinitrophenol) will inhibit completely the propagation of influenza virus in chorioallantoic membrane. This reagent did not permanently alter those metabolic processes required for the synthesis of virus and at the concentrations employed demonstrated no virucidal effects.

In minced preparations of chorioallantoic membrane DNP was shown to have a pronounced stimulatory effect upon ATPase (adenosinetriphosphatase).

When DNP was used with intact tissues, an excellent correlation was found between the inhibition of viral propagation and the stimulation of respiration and release of phosphate.

Concentrations of DNP which permitted a twofold increase in the endogenous respiration of intact membranes allowed little or no viral synthesis.

It is concluded that the energy required for viral synthesis derives from the oxidative phosphorylative activity of the host tissue.
WATER EXCHANGE OF COLLAGENOUS TISSUES AND OF GELATIN
Authors: Opie Eugene L. , Rothbard Mary B.
Published: June 2004

Water exchange of parenchymatous tissue, namely liver, kidney, or pancreas, occurs by osmosis, and the movement of water, as is well known, occurs in direct relation to the concentration of the surrounding solution. But the present work shows that the hydration of collagenous tissues, like that of gelatin, occurs in strong as well as in weak solutions of sodium chloride.

The water intake of collagenous tissue in solutions of sodium chloride or of sucrose increases with increased density of the tissue and the sequence of changes is like that observed with gels of increasing gelatin content under the same conditions.

Dense collagenous tissue, apparently impervious to the movement of water, exhibits a conspicuous ability to attract and hold it.
THE EFFECT OF TEMPERATURE ON THE GROWTH OF VIRUS-INDUCED FROG CARCINOMA
Authors: Lucké Balduin , Berwick Leonard , Nowell Peter
Published: June 2004

The temperature coefficient of van't Hoff, Q10, for growth of frog carcinoma in vitro over a range of 20–35°C, averages 2.5. This value is closely similar to those obtained for various forms of normal growth.

The values of the temperature coefficient slightly but progressively decrease with advancing age of the cancer colonies. A similar relation obtains in many but not in all forms of normal growth.

Thus, the law of van't Hoff is found to hold equally for growth of the malignant tissue now under discussion and for normal tissue.
OBSERVATIONS CONCERNING THE PRODUCTION AND EXCRETION OF CHOLESTEROL IN MAMMALS
Authors: Byers Sanford O. , Friedman Meyer , Biggs Max W. , Gunning Barbara
Published: June 2004

Accumulation of cholate in plasma is the immediate cause of hypercholesteremia in the rat with bile duct ligation and in the normal rat given intravenous sodium cholate.

The hypercholesteremia induced by cholate administration does not appear to be dependent upon any preceding change in the rates of absorption, excretion, synthesis, or redistribution of cholesterol in the tissues of the animal.

Cholate administration seems to induce hypercholesteremia by impeding the normal rate of passage of cholesterol from the plasma into the liver; this impedance is probably due to an alteration of the cholesterol-binding power of plasma proteins induced by cholate. The chemical and physiological implications of this finding are discussed.
THE INACTIVATION OF COMPLEMENT AND ITS COMPONENTS BY PLASMIN
Authors: Pillemer Louis , Ratnoff Oscar D. , Blum Livia , Lepow I. H.
Published: June 2004

Human complement is inactivated by plasmin, the proteolytic enzyme of plasma or serum active at or near neutrality.

The addition of streptokinase to human serum, which converts plasminogen to plasmin, also causes the inactivation of complement components C'2 and C'4 and varying amounts of C'1. C'3 is the most resistant to inactivation by plasmin. Chloroform-activated human plasmin and bovine plasmin also destroy these components of complement, but are less effective than the streptokinase-activated enzyme. The inactivation of complement by the addition of streptokinase to human serum is inhibited by high hydrogen ion concentrations, low temperature, and elevated ionic strength. The inactivation of the components of complement in various fractions of serum is influenced by the available plasminogen and the content of plasmin inhibitors in these fractions.

Certain similarities are pointed out between the components of complement and the factors in the plasmin system and between the inactivation of the components of complement by antigen-antibody reactions, by specific agents, and by plasmin.

The possible significance of these relationships in immune hemolysis and complement fixation, and the possible role of the plasmin system in the instability of complement and the development of anticomplementary properties in serum are discussed.
AN ANTIVIRAL SUBSTANCE FROM PENICILLIUM FUNICULOSUM
Authors: Shope Richard E.
Published: June 2004

Helenine is moderately stable in solution at refrigerator temperature and can be kept for long periods of time without evident loss of activity if stored frozen at the temperature of solid CO2. It is filterable through a Seitz pad but not dialyzable. Crude SPS preparations of helenine do not lose activity when dried from the frozen state. Some conditions are described, however, which influence the preservation or inactivation of acetone-precipitated helenine when freeze-dried. Helenine is partially inactivated by exposure for 3 minutes to the temperature of a boiling water bath and is completely inactivated by autoclaving at 15 pounds' pressure for 15 minutes.

The data presented suggest that helenine acts, either directly or by triggering some mechanism of the host itself, to destroy virus by a process which renders the latter non-antigenic. This effect may be exerted by action upon the virus itself or by interference with some stage in the developmental cycle of the virus.

While the chemical nature of helenine is not known, the presence of a large proportion of polysaccharide in crude active preparations might suggest the possible importance of this class of substance in helenine activity. It is believed that helenine differs from the polysaccharide reported by Horsfall and McCarty and the penicillin impurity reported by Groupé and Rake to be active against certain viruses. It may be related, however, to the antiviral substance recently reported by Powell and his co-workers.
STUDIES ON THE GENERALIZED SHWARTZMAN REACTION
Authors: Thomas Lewis , Denny Floyd W. , Floyd Joan
Published: June 2004

Cutaneous and systemic infections of rabbits by Group A streptococci bring about a state of preparation for, respectively, the local and generalized Shwartzman reactions, produced by intravenous injection of meningococcal or S. marcescens toxin.

With maximal systemic streptococcal infections, the lesions of the generalized Shwartzman reaction do not differ from those caused by two successive intravenous injections of Gram-negative bacterial toxins. The characteristic lesions of the reaction are bilateral cortical necrosis of the kidneys, hemorrhagic necrosis in the lungs, liver, and spleen, and myofiber necrosis in the myocardium.

Under optimal conditions involving the dosages of streptococci and toxin, and the time interval between the injections, a new lesion consisting of necrosis and the accumulation of fibrinoid material in the walls of the coronary arteries occurred in approximately 50 per cent of animals within 48 hours after the injection of meningococcal toxin.

Fibrinoid necrosis was not observed in the arteries of tissues other than the heart. It did not occur in control rabbits injected with streptococci alone or toxin alone, nor in animals with the generalized Shwartzman reaction produced by two intravenous injections of toxin.

Streptococcal bacteriemia was present at the time of death in one-third of the animals with fibrinoid necrosis. In one animal, a group of bodies resembling cocci in chains was seen within the wall of a coronary artery with fibrinoid necrosis.

A series of photomicrographs to illustrate the pathological changes in the hearts and kidneys of streptococcus-infected rabbits subjected to the Shwartzman reaction is presented.
CONTROL BY FACTORS DISTINCT FROM THE S TRANSFORMING PRINCIPLE OF THE AMOUNT OF CAPSULAR POLYSACCHARIDE PRODUCED BY TYPE III PNEUMOCOCCI
Authors: MacLeod Colin M. , Krauss Marjorie R.
Published: June 2004

Pneumococci can possess the normal S transforming principle and yet produce amounts of capsular polysaccharide much less than would be expected if the quantity formed depended only on the nature of the S transforming principle.
TRANSFORMATION OF TYPE SPECIFICITY OF MENINGOCOCCI
Authors: Alexander Hattie E. , Redman Winifred
Published: June 2004

Heritable type-specific traits have been induced in meningococcus populations by exposure to desoxyribonucleic acid (DNA)-containing extracts derived from meningococcus cells of the type desired. The DNA has been shown to be an essential component of the transforming extract.

As in the H. influenzae system, the reaction between the susceptible cell and the DNA responsible for the heritable change requires less than 15 minutes. Only a minute proportion of the total cells exposed to the DNA extracts for a short time are susceptible to the change; but in the growth and reproduction of bacteria susceptible cells appear with fairly predictable frequency.

Type I specific traits have been induced in populations of RIIa and SIIa cells.

Type IIa specificity has been induced in RIIa cells.
NEUTRALIZATION OF VIRUSES BY HOMOLOGOUS IMMUNE SERUM
Authors: Tyrrell David A. J.
Published: June 2004

On the assumption that antibody is added to virus particles in a stepwise manner and that the reaction follows the law of mass action, a theoretical equation for the equilibrium state of virus neutralization reactions has been deduced.

The theory has been found to be in reasonable accord with the available data for the neutralization of bacterial viruses and can be applied also to data for the neutralization of animal viruses.
STUDIES ON HOST-VIRUS INTERACTIONS IN THE CHICK EMBRYO-INFLUENZA VIRUS SYSTEM
Authors: Liu Oscar C. , Henle Werner
Published: June 2004

Equal mixtures of influenza A (PR8) and B (Lee) viruses, based on predetermined ID50 values of the individual preparations, were titrated in closely spaced steps near the 50 per cent infectivity end-point. Typing of the hemagglutinins found in the allantoic fluids after incubation of the eggs for 72 hours showed an approximately equal distribution between types A and B, when less than 2 ID50 of the mixed seed had been injected. With larger inocula influenza A became dominant because it reproduces at a faster rate than the influenza B virus. While this result agreed with expectations, it was found that passage of the allantoic fluids revealing influenza A agglutinins in mixture with anti-A serum, and of B agglutinins with anti-B, yielded the heterologous virus in many instances, even when only one-half of an ID50 of mixed seed had been administered in the original titration. "Negative" fluids obtained from embryos injected with as little as one-eighth of an ID50 upon passage yielded on occasion virus of one or the other type.

Similar closely spaced titrations near the 50 per cent end-point of single strains (PR8) indicated that if hemagglutinins were found after incubation of 72 hours they were of high titer, as a rule. However, in some embryos hemagglutinins became detectable only between the 3rd and 4th days of incubation. In addition, negative allantoic fluids removed from embryos 72 hours after injection yielded on occasion virus on passage, yet no hemagglutinins were found in some of these eggs after an additional incubation period of 24 hours, or a total of 96 hours.

None of the possible explanations for these various observations, which have been discussed in detail, is completely satisfactory. However, the data indicate that in infectivity titrations the ID50 end-point obtained at 72 hours, or even after 96 hours, does not reflect the total amount of virus present in the material titrated. The data also denote that separation of variants, or mutants or "genetic recombinants" by the limiting dilution technic, although possible, does not represent an absolutely safe procedure.
MORPHOLOGIC VARIATION IN PNEUMOCOCCUS
Authors: Austrian Robert
Published: June 2004

The problem of morphologic variation in pneumococcus has been reviewed and the desirability of studying such variation through an examination of bacterial cells rather than of bacterial colonies has been pointed out. To further this objective, a new terminology to describe the morphologic variants of pneumococcus, potentially applicable to other bacterial species, has been proposed.

A hitherto undefined morphologic variant of pneumococcus, the filamentous capsulated (fil+ S+) variant, has been defined and its relationship to the three previously recognized non-filamentous capsulated (fil- S+), nonfilamentous non-capsulated (fil- S-), and filamentous non-capsulated (fil+ S-) variants has been presented.
THE EXPERIMENTAL PRODUCTION OF COMBINATION FORMS OF VIRUS
Authors: Hirst George K. , Gotlieb Tamar
Published: June 2004

The fact that the hemagglutination inhibition test will not detect more than one component in an artificial mixture of two antigenically distinct strains of virus was demonstrated experimentally. With this proved, the inference seemed justified that the inhibition of the hemagglutinin of a virus suspension by each of two antisera, specific for differing strains of virus, would be an indication that some of the specific antigenic components from each of these viruses were both present in single particles of the virus suspension.

Two pair of influenza A strains were used to simultaneously inoculate the allantoic sac, and some embryos thus infected yielded virus which had its hemagglutinin inhibited by sera specific against each of the parent forms. Such doubly inhibitable hemagglutinin contributed as much as 84 per cent of the total hemagglutinin in certain fluids. Each of the specific antisera inhibited the hemagglutinin of the combination form very nearly as well as it inhibited its own hemagglutinin.
THE EXPERIMENTAL PRODUCTION OF COMBINATION FORMS OF VIRUS
Authors: Hirst George K. , Gotlieb Tamar
Published: June 2004

Double infection of the allantoic sac with Melbourne and WSN viruses induced the formation of a combination virus, which had some of the antigenic properties of both parents and which maintained itself through serial passage in the chorioallantoic sac. In the course of prolonged passage in the egg, three varieties of combination virus were found. The first (X1) occurred in ten passages and was characterized as follows: X1 was produced in and could be successfully passed from those chick embryos that had received very large inocula of virus. The X1 hemagglutinin was efficiently inhibited by both M and W antisera. Each passage fluid, containing X1 as the predominant strain, also contained large amounts of the parent forms M and W. It is very likely that X1 reverted to parent types of virus at a high rate.

The second variety (X2) arose from the passage series of X1 and was carried for approximately 20 passages without definite alteration in its character. It differed from X1 in that it had the ability to appear as the predominant form occasionally in embryos that had received a limiting infective dilution of virus. Because of this, it seems probable that X2 reverted to parent types at a slower rate than X1. Like X1, this virus was never obtained in pure form and suspensions in which it predominated contained large amounts of M and W, especially the former. Good evidence was obtained that X2 reverted to M and W virus while multiplying in the chorioallantoic sac.

X3 was derived from passage of X2 virus after 32 transfers and can be characterized in several ways: (a) X3 yielded the only X3 fluids on passage in eggs. This was in striking contrast to X2 which could not be passed without giving rise to some fluids in which M and W predominated, (b) The X3 hemagglutinin was weakly inhibited by all but the highest concentrations of M serum, but was strongly inhibited by W serum. X2 was readily inhibited by relatively small amounts of both sera. (c) X3 virus, after several passages at limiting dilutions, was neutralized to a highly significant degree by specific M and W sera. This is not necessarily an essential difference from the behavior of X2 since technical difficulties (large amounts of M and W in X2 fluids) may have prevented the demonstration of equally striking double neutralization of this virus, (d) After five limiting dilution passages, the X3 virus retained the characteristics listed under (a) to (c). It is felt that the foregoing facts justify the conclusion that X3 is a stable virus which combines some of the specific antigens of two parent types.
EFFECT OF KETONE BODIES AND OTHER METABOLITES ON THE SURVIVAL AND MULTIPLICATION OF STAPHYLOCOCCI AND TUBERCLE BACILLI
Authors: Dubos René J.
Published: June 2004

A study has been made of the fate of staphylococci and tubercle bacilli resuspended in aqueous media at slightly acid reactions. The tests were carried out at several acid reactions in balanced ionic media containing 0.5 per cent serum albumin. These experimental conditions were selected in order to approximate those which are probably encountered by pathogenic agents in inflammatory areas and in the intracellular environment of the leucocytes after phagocytosis.

The viability of the microorganisms at a given pH was markedly influenced by the composition of the medium, being decreased by addition to the latter of lactic, acetic, propionic, and butyric acids, and increased by the addition of certain ketone bodies such as dihydroxyacetone and pyruvic, ß-hydroxybutyric, α-ketoglutaric, and oxalacetic acids.

The presence of ketone bodies in the medium afforded to the microorganisms some protection against the bactericidal effect of lactic and acetic acids at acid reactions.

The minimum and the optimum pH for growth were found to be dependent on the composition of the medium. Both were higher in the presence of lactic, acetic, propionic, and butyric acids than in the media without organic acids added. In contrast, the addition of ketone bodies to the medium allowed microbial multiplication even in acid media (approximately at pH 5.3 or even lower).

The fact that lactic acid antagonizes, whereas ketone bodies favor, the survival and multiplication of staphylococci and tubercle bacilli at acid reactions, is discussed in relation to the high susceptibility to infection which is often associated with ketosis of various etiology.
INTRACELLULAR FORMS OF POX VIRUSES AS SHOWN BY THE ELECTRON MICROSCOPE (VACCINIA, ECTROMELIA, MOLLUSCUM CONTAGIOSUM)
Authors: Gaylord William H. , Melnick Joseph L.
Published: June 2004

The intracellular development of three pox viruses has been studied with the electron microscope using thin sections of infected tissue.

Cells infected with vaccinia, ectromelia, and molluscum contagiosum viruses all form developmental bodies preliminary to the production of mature virus. Developmental bodies, believed to be virus precursors, are round to oval, slightly larger than mature virus particles, less dense to electrons, and have a more varied morphology.

It is suggested as a working hypothesis that the process of maturation of a virus particle takes place as follows. In the earliest form the developmental bodies appear as hollow spheres, imbedded in a very dense cytoplasmic mass constituting an inclusion body, or in a less dense matrix near the nucleus in cells without typical inclusion bodies. The spheres become filled with a homogeneous material of low electron density. A small, dense granule appears in each developmental body and grows in size at the expense of the low density material. Following growth of the granule, particles are found with the dimensions of mature virus and having complex internal structure resembling bars or dumbells. Mature virus is ovoid and very dense to electrons. An "empty" interior may be found within its thick walls.
EFFECT OF INFECTION WITH M. TUBERCULOSIS AND OF TUBERCULIN SHOCK ON THE SUCCINIC DEHYDROGENASE ACTIVITY OF GUINEA PIG TISSUES
Authors: Chaudhuri S. N. , Martin Samuel P.
Published: June 2004

The kidney of guinea pigs infected with the H37Rv and BCG strains of M. tuberculosis showed a diminution in succinic dehydrogenase activity when measured by the tetrazolium technique. This effect was also seen in the liver and spleen of animals infected with the BCG strain. Sensitized animals showed similar results when given tuberculin in sublethal doses. The succinic oxidase was also low in the kidneys of animals infected with the H37Rv strain.

The depressed enzyme activity of the tissues of infected animals could be restored to normal by addition of normal tissue extract or dialysate. This suggests that the alteration in tissue metabolism observed in tuberculosis may depend upon the loss of some as yet unidentified factor important for succinic dehydrogenase activity.
INHIBITION OF INFLUENZA VIRUS MULTIPLICATION BY ALKYL DERIVATIVES OF BENZIMIDAZOLE
Authors: Tamm Igor , Folkers Karl , Horsfall Frank L.
Published: June 2004

At a concentration of 0.0026 M, 2,5-dimethylbenzimidazole caused a number of alterations in the first cycle of multiplication of influenza B virus, Lee strain, in chorioallantoic membrane cultures in vitro. As determined by infectivity titrations in ovo on the membrane per se, the following alterations were observed: The duration of the latent period was increased by 80 per cent. The rate of increase in titer during the incremental period was somewhat decreased. The yield of virus was decreased by about 99 per cent.

When the compound was added to membrane cultures at various periods before or after inoculation with the virus, the following findings were obtained: On addition before or along with the virus, the substance caused about 99 per cent inhibition of multiplication. When added during the first 2 hours after inoculation, the compound caused inhibition of a degree which was inversely proportional to the time of addition. When added 3 to 8 hours after inoculation, the substance caused about 80 per cent inhibition. When added after the end of the latent period, no definite inhibition was obtained in the first cycle of multiplication.

These results are interpreted as indicating that 2,5-dimethylbenzimidazole acts by reducing the rate of biosynthetic mechanisms necessary for the reproduction of influenza virus particles.