bluuebunny/crossref_metadata_2025 huggingface dataset:
REGULATION OF CHOLESTEROL SYNTHESIS IN THE LIVER: THE INFLUENCE OF DIETARY FATS
Authors: Linazasoro José M. , Hill R. , Chevallier François , Chaikoff I. L.
Published: June 2004

Rats were fed, for 3 days, four synthetic diets, all of which contained the same proportion of carbohydrate (50 per cent) and were of equal caloric value per gram. These diets contained either 0 or 15 per cent fat. The fats used were lard, corn oil, Wesson oil, and a hydrogenated vegetable oil. The feeding of the fat-containing diet for 3 days increased the liver's capacity for incorporating acetate carbon to cholesterol. The fats tested were of about equal value in stimulating hepatic cholesterogenesis.

The various diets fed had no effect on the lipide or glycogen content of the liver nor on the lipide content of plasma.
EARLY CHANGES AT THE EPIPHYSIS OF RACHITIC CHICKS, FOLLOWING ADMINISTRATION OF VITAMIN D
Authors: Bélanger Leonard F. , Migicovsky B. B.
Published: June 2004

One day old chicks were fed a vitamin D-deficient diet for 3 weeks. Some were then given an oral dose of vitamin D and sacrificed at various times thereafter. The tibiae were x-rayed; demineralized sections were stained for neutral polysaccharides and sulfated mucopolysaccharides; other specimens were ashed; and others still were autoradiographed to determine their uptake of Ca45 in vitro.

Mineralization reappeared in the treated animals after 2 days, along with new P.A.S.-positive spicules.

Earlier, the immature cartilage rapidly matured morphologically. At the same time, the rachitic matrix, highly concentrated in cation binder, presumably chondroitin sulfate, lost this material progressively.
ANTIGENIC VARIANTS OF INFLUENZA A VIRUS (PR8 STRAIN)
Authors: Loosli Clayton G. , Hamre Dorothy , Gerber Paul
Published: June 2004

Two series of variants of influenza PR8-S virus have been described. While all retain the same degree of pathogenicity for mice and fertile eggs, there was a progressive loss in the ability of the variants to provoke antibody following vaccination or infection of mice and ferrets. The immunogenicity of the variants was, therefore, less than that of the original strain. Although little or no serological relationship could be demonstrated between some of the variants and the PR8-S virus a considerable degree of cross-immunity could be demonstrated in the cross-protection tests with these viruses if observations were based solely on death or survival of the mice. By employing the occurrence of lesions in the lung and the titer of virus in the lung 48 hours after challenge, the amount of cross-protection in mice could be related to the amount of serological cross-reaction. In general mice vaccinated with PR8-S virus were less resistant to infection with the variant viruses than mice vaccinated with variants and challenged with the PR8-S parent virus.

The role of the immune environment of the host in the production of the variant influenza viruses with their serological differences, decreasing antigenicity, and persisting pathogenicity as well as the epidemiological implications of these findings with respect to epidemic influenza in man are discussed.
CHARACTERIZATION OF THE "REACTANT" (GAMMA GLOBULIN FACTOR) IN THE F II PRECIPITIN REACTION AND THE F II TANNED SHEEP CELL AGGLUTINATION TEST
Authors: Christian Charles L.
Published: June 2004

The material in gamma globulin ("reactant") which reacts with rheumatoid sera in the F II precipitin and F II tanned sheep cell agglutination tests was concentrated by precipitation with sodium sulfate. The concentrated "reactant" appeared to consist of polydispersed molecular aggregates of gamma globulin with s20 constants as high as 40, as well as the previously described inhomogeneous aggregated material.

Aggregated gamma globulin precipitated readily with most rheumatoid sera regardless of the reaction volume, and in low concentration inhibited the F II tanned sheep cell agglutination reaction and sensitized tanned erythrocytes to the agglutinating action of a positive rheumatoid serum. On the other hand, non-aggregated gamma globulin (7S) did not precipitate with rheumatoid sera and in low concentration did not inhibit the F II tanned sheep cell agglutination reaction, or sensitize tanned erythrocytes.

Non-aggregated gamma globulin in large excess inhibited the precipitin reaction of aggregated gamma globulin with "rheumatoid factor," and accounted for the characteristic shape of the whole F II precipitin curves and the volume effect described by Vaughan (relation of increased precipitate yield relative to the reaction volume in whole F II precipitin studies).

In serological systems other than the F II tanned sheep cell and F II precipitin reactions, the sensitization involves an antigen-antibody combination; i.e., sheep erythrocyte plus hemolysin in the sensitized sheep cell test, and egg albumin plus anti egg albumin in the absorption experiments with specific precipitates. The aggregation of gamma globulin that was essential for sensitization in the F II tanned sheep cell and F II precipitin tests may have simulated the aggregation of antibody gamma globulin that occurs with antigen-antibody union.

The present information has been incorporated into a schematic hypothesis for the basis of the rheumatoid serological reactions.
ACTIVATION OF QUIESCENT MUCORMYCOTIC GRANULOMATA IN RABBITS BY INDUCTION OF ACUTE ALLOXAN DIABETES
Authors: Sheldon Walter H. , Bauer Heinz
Published: June 2004

In normal rabbits subcutaneous granulomata produced by the injection of a spore suspension of Rhizopus oryzae remained confined to the site of inoculation, showed no fungus proliferation, no longer yielded the agent on culture 10 weeks after inoculation, and eventually healed. Similar well established granulomata in rabbits with acute alloxan diabetes induced 8, 10, and 15 days after injection of the fungus uniformly showed activation of the infection. This occurred only in animals showing acetonuria. In these animals the skin lesions showed proliferation of the fungus frequently associated with invasion and early necrosis of the granuloma wall. In some instances, spread of the infection to adjacent tissues with invasion of blood vessels had occurred. These experiments illustrate that changes in host metabolism can activate a preexisting quiescent infection.
STUDIES OF THE PLASMIN SYSTEM
Authors: Norman Philip S.
Published: June 2004

The inactivation of purified plasmin by serum or plasma was studied using a caseinolytic assay for determination of plasmin. On the basis of kinetic evidence, the presence of two inhibitors in normal human or guinea pig serum or plasma is suggested. The first reacts immediately at any temperature, but is easily dissociable and does not combine with plasmin in a fixed ratio. The second combines more slowly with plasmin at a rate which depends on temperature and on the concentration of both plasmin and inhibitor. There is a fixed ratio of reaction between plasmin and the second inhibitor and the combination does not readily dissociate. There is sufficient of the "slow" inhibitor in normal plasma to inactivate more than 30 times its own content of potential plasmin. The presence of suitable substrate for plasmin tends to reverse the combination with "immediate" inhibitor and to stop the further action of "slow" inhibitor.
EFFECT OF DIETARY PROTEINS AND AMINO ACIDS ON THE SUSCEPTIBILITY OF MICE TO BACTERIAL INFECTIONS
Authors: Dubos René J. , Schaedler Russell W.
Published: June 2004

Groups of young albino mice were fed continuously four different types of diets and were compared with regard to (1) rate of weight gain; (2) resistance to experimental bacterial infections.

The protein content of the four diets was as follows: (a) pellets: a minimum of 21 per cent "crude" protein (according to the manufacturer); (b) diet 20 C: 20 per cent casein; (c) diet 8 C: 8 per cent casein; (d) diet 8 C + AA: 8 per cent casein supplemented with 12 per cent of a mixture of essential amino acids. All diets provided an adequate supply of minerals and vitamins. They were administered ad lib.

Three strains of pathogens virulent for mice were used for the infection tests, namely: Staphylococcus aureus, Mycobacterium fortuitum, and Mycobacterium tuberculosis bovis. The bacteria were injected by the intravenous route.

The experimental regimens were begun at different times before infection, and were continued until death of the animal, or until termination of the experiment.

It was found that mice on the 8 C diet exhibited much greater susceptibility to infection than did mice on the 20 C diet; mice receiving pellets were intermediate between these two groups. The infection-enhancing effect of the 8 C diet could be entirely corrected by amino acid supplementation (diet 8 C + AA). Indeed, mice fed diet 8 C + AA proved the most resistant to infection.

The fact that animals fed pellets (which contain a minimum of 21 per cent protein) consistently died faster following infection than did animals fed diets 20 C or 8 C + AA suggests that qualitative characteristics of the protein in the regimen are as important as the quantity of protein fed in determining susceptibility to infection.

The differences in susceptibility exhibited by the mice on the four experimental diets were the same whatever the species of bacterial pathogen used for the infection test, the size of the infective dose, and the duration of the disease.

There was no apparent relation between the effects of the diets on the weight curves of the animals, and on resistance to infection. Mice on diet 8 C (which were most susceptible) gained weight as rapidly as those on 20 C and more rapidly than those fed 8 C + AA (which were most resistant).

All the tests reported in the present paper were carried out with young mice, which were placed on experimental diets within 1 to 2 weeks after weaning. Preliminary experiments suggest that the relation between dietary factors and susceptibility to infection was more difficult to bring out in older animals. There was evidence also that this relation was most apparent during the first weeks that the animals were fed the experimental diets, and became less striking after several weeks.
INHIBITION OF TUBERCULIN SKIN HYPERSENSITIVITY IN GUINEA PIGS BY INJECTION OF TUBERCULIN AND INTACT TUBERCLE BACILLI DURING FETAL LIFE
Authors: Weiss David W.
Published: June 2004

Female guinea pigs were subjected to laparotomy at different stages of pregnancy, and their fetuses injected through the uterine walls with one of the following preparations: Old Tuberculin, tubercle bacilli of the BCG strain killed by heat or exposure to phenol, and living BCG.

A large number of the animals injected in utero with Old Tuberculin failed to develop skin hypersensitivity to P.P.D. following vaccination with 200 or 800 γ phenol-killed tubercle bacilli (BCG) in early adulthood. Normal control animals were sensitized by vaccination with such quantities of phenolized BCG. The failure of animals which had been injected with Old Tuberculin in fetal life to respond hypersensitively to P.P.D. after adult vaccination with tubercle bacilli is ascribed to their acquisition of a state of immunological tolerance to tuberculoprotein (tuberculin tolerance).

Fetal injection with killed BCG conferred a state of tolerance on a few of the animals, and rendered others tuberculin-sensitive. Fetal injection with living BCG sensitized most of the animals to tuberculin, even when fetal exposure was as early as 46 days before birth, and induced tolerance in none.

Fetuses of the same litter, injected simultaneously with identical inocula, often responded differently, some becoming tolerant to tuberculin, others developing hypersensitivity, and still others remaining immunologically unaffected, becoming neither sensitive nor tolerant.

The state of tuberculin tolerance induced in these experiments was limited. When tolerant animals were revaccinated with living BCG several weeks after vaccination with phenol-killed bacilli, they developed as high a degree of tuberculin skin sensitivity as the originally non-tolerant animals.
ARTHROPOD TRANSMISSION OF RABBIT PAPILLOMATOSIS
Authors: Dalmat Herbert T.
Published: June 2004

The virus of rabbit papillomatosis, a neoplastic disease studied intensively in relation to cancer because of its tendency toward malignant transformation, has been successfully transmitted by Aedes aegypti, Rhodnius prolixus, and Triatoma infestans from papillomas induced in cottontail rabbits, and by the first species mentioned, from papillomas induced in domestic rabbits. This was accomplished by interrupted feeding, feeding after an interval of several days from the infective meal, or by application of a suspension of the mouthparts of the insects either immediately after their infective meal or several days later.

Insect transmission was also successful from the satellite growths resulting from subcutaneous extensions of the typical papillomas of infected cottontails, and from certain peculiar, subcutaneous nodules, arising rapidly after infection, and not heretofore described. Although the latter growths resembled rabbit fibromas, antibodies to fibroma virus could not be demonstrated by neutralization tests with the sera of the animals involved.
STUDIES IN THE PATHOGENESIS OF LUPUS ERYTHEMATOSUS
Authors: German James L.
Published: June 2004

Hematoxyphil bodies, both in appearance and staining characteristics resembling those seen in the kidney of the patient with systemic lupus erythematosus, have been produced in experimental animals. Kidneys examined from 15 minutes to 4 hours following intra-aortic injection of L.E. cells and L.E. bodies have exhibited these Feulgen-positive bodies in the glomerular capillaries. Control injections have given completely negative results.
STUDIES ON THE FORMATION OF COLLAGEN
Authors: Gross Jerome
Published: June 2004

Precipitation (or gelation) of collagen from cold neutral salt solution induced by warming was shown to be reversible on subsequent cooling. The degree of reversibility of heat precipitation rapidly diminished with time of incubation at 37°C. For calf skin collagen (acetic acid-extracted) and guinea pig skin collagen (crude NaCl extract) in neutral salt solutions (Γ/2 = 0.45) roughly 90 per cent of newly formed gel redissolved on cooling at 2°C.; less than 20 per cent redissolved on cooling gels previously maintained at 37°C. for 24 hours. At physiologic ionic strength the same preparations exhibited much more rapid development of irreversible precipitation, but the same time dependence was clearly evident. Highly purified collagen from crude saline extracts of guinea pig skin exhibited the same phenomenon although the quantitative aspects were somewhat different.
THE SYNTHESIS OF A TETRADECAPEPTIDE RENIN SUBSTRATE
Authors: Skeggs Leonard T. , Lentz Kenneth E. , Kahn Joseph R. , Shumway Norman P.
Published: June 2004

A tetradecapeptide renin substrate having a biological activity comparable to the natural product and similar chemical properties has been synthesized by means of the carbobenzyloxyl azide and mixed anhydride methods.
A COMPARISON OF THE EFFECTS ON THE SHWARTZMAN PHENOMENON OF LEUKOPENIA PRODUCED BY NITROGEN MUSTARD AND BY WHOLE BODY IRRADIATION
Authors: Johnstone Douglas E. , Howland Joe W.
Published: June 2004

The effect of leukopenia on the susceptibility of rabbits to the localized Shwartzman reaction was studied in those receiving whole body irradiation and nitrogen mustard respectively. Of animals receiving nitrogen mustard in which the total polymorphonuclear leukocyte count was less than 100 cells/c.mm. only 17 per cent developed positive local Shwartzman reactions whereas 75 per cent of irradiated animals with total polymorphonuclear leukocyte counts less than 100 cells/c.mm. had positive reactions. A local Shwartzman reaction occurred in 60 of 71 control rabbits (85 per cent). Animals of both the treated groups showed positive Shwartzman reactions at a time when their total polymorphonuclear leukocyte counts were less than 500 cells/c.mm.

From the findings, it is concluded (a) that the presence of normal numbers of circulating polymorphonuclear leukocytes is not an obligatory prerequisite condition to the localized hemorrhagic necrosis of the Shwartzman phenomenon, and (b) the mechanisms of action of nitrogen mustard and whole body irradiation on body tissues differ in relation to the Shwartzman reaction.
STUDIES ON PERSISTENT INFECTIONS OF TISSUE CULTURES
Authors: Henle Gertrude , Deinhardt Friedrich , Bergs Victor V. , Henle Werner
Published: June 2004

Inoculation of the MCN and Lung-To lines of human cells in continuous culture with Newcastle disease (NDV), mumps, or 6-6 viruses led to slight cytopathic effects (CPE) if the multiplicity of infection exceeded one. On second passage or with smaller initial inocula no CPE became apparent. The viruses multiplied, however, as determined by titrations in HeLa cultures or chick embryos. Indeed, persistently infected sublines of MCN and Lung-To were readily established without resort to special manipulations and some of these have been carried now for over 18 months on the same media and schedules as the uninfected parent strains.

The viruses were found to be associated mainly with the cells and only 1, or at most 10 per cent of it was detectable in the media. The titers obtained were always low in relation to the available cell population.

Reduction or even omission of the horse serum component in the media or ultraviolet irradiation of the cultures did not increase the yield of virus, and CPE became apparent only when similarly treated, uninfected cultures were, likewise, affected by the manipulations.

The persistently infected cultures differed from their uninfected counterparts in that they exhibited (a) decreased cellular growth rates and ultimate yields; (b) increased aerobic glycolysis; and (c) a high degree of resistance to cytopathogenic viruses, influenza A (PR8), herpes simplex and, especially vesicular stomatitis (VSV) viruses.

Prolonged treatment of persistently infected cultures by addition of specific antiviral immune sera to the media reduced significantly the amount of virus present and the degree of resistance to VSV. However, upon removal of the sera after as many as 187 days of treatment the viruses reappeared in all but one instance. The cured culture, on reinfection, became again persistently infected.

No evidence was obtained to indicate genetic inhomogeneity of the cell populations. Of 50 cloned MCN lines none was destroyed by NDV and all became persistently infected. None were initially resistant to VSV but all after establishment of persistent NBV infection. All 39 cloned lines derived from MCNNDV cultures in the presence of anti-NDV serum, were free of virus and susceptible to VSV, and all acquired persistent infections and with it resistance to VSV following inoculation of NDV.

NDV maintained in MCN cultures differed from the parent, chick embryo-adapted strain with respect to its plaque morphology. Whereas the former yielded only plaques on monolayers of chick embryo fibroblasts which were of pin-point size and hazy, those obtained with the latter were rarely of this type and mostly large and clear. This apparent selection of virus particles did not alter significantly their behavior with respect to cytopathogenicity for uninfected MCN cultures.
POLIOMYELITIS AS A COMPLEX INFECTION
Authors: Dalldorf Gilbert , Weigand Heribert
Published: June 2004

Young cynomolgus monkeys inoculated intracerebrally with an attenuated Type 1 polio virus and, after 5 days, with a monkey adapted Coxsackie A-14 virus frequently became paralyzed. Neither virus alone was capable of inducing paralysis.

Similar results were observed when the AB IV strain of Coxsackie A-7 was substituted for the A-14 virus. In this case the 2nd inoculation was made intramuscularly.

Paralytic poliomyelitis may at times represent the summation of two infections, the total of motor neuron destruction by two independent and noninterfering enteroviruses.
ENZYMATIC VARIANTS OF INFLUENZA VIRUS
Authors: Padgett Billie L. , Walker Duard L.
Published: June 2004

The rate of elution of the variant virus from chicken RBC is progressively decreased as the temperature of incubation is increased above 25°C. The activity of the parent virus, on the other hand, is increased as the temperature is increased up to 40°C. The major cause of the decreased activity of the variant at temperatures above 2S°C. is an inhibition of the variant enzyme rather than its inactivation.

The activity of the variant enzyme is stimulated in the presence of strontium, calcium, and barium ions. Manganese has only a slight effect, and magnesium has no stimulatory effect on the elution of the variant virus.

Elution of the variant at 37°C. is progressively inhibited at pH values above 7, while the parent virus is still active at pH 8.

In the absence of calcium the variant enzyme, hemagglutinin, and infectivity are more heat labile than those of the parent virus. The addition of calcium increases the heat stability of all three properties of the variant, and in the presence of calcium the infectivity of the variant is as stable as that of the parent virus.
INACTIVATION OF ENDOTOXIN BY A HUMORAL COMPONENT
Authors: Rosen Fred S. , Skarnes Robert C. , Landy Maurice , Shear Murray J.
Published: June 2004

The uniformly high potency of citrated plasma as compared with the limited capacity of serum to inactivate endotoxin in vitro was found to be a consequence of the anticoagulant employed in collecting the plasma.

Addition of calcium to plasma suppressed the activity of its endotoxm detoxifying component (EDC) whereas the addition of calcium-binding anticoagulants rendered serum comparable to plasma.

Dialysis of plasma resulted in a marked reduction of its EDC activity despite the concommittant elimination of calcium. EDC activity could then be fully restored upon the addition of calcium-binding anticoagulants.

Resin-treated plasma, without added anticoagulant, had EDC activity equal to plasma obtained with calcium-binding anticoagulants. Following dialysis, resin-treated plasma also sustained a marked reduction in EDC activity which could be fully restored by calcium-binding anticoagulants. Restoration was also obtained with the dialysate even after ashing.

These findings indicated that the suppression of EDC activity by calcium is not direct but is mediated through its effects on an anionic component of plasma which is required for inactivation of endotoxin by EDC.
CHARACTERIZATION OF A FACTOR FORMED IN THE COURSE OF ADENOVIRUS INFECTION OF TISSUE CULTURES CAUSING DETACHMENT OF CELLS FROM GLASS
Authors: Rowe Wallace P. , Hartley Janet W. , Roizman Bernard , Levy Hilton B.
Published: June 2004

Infectious tissue culture fluids of the majority of serotypes of adenovirus at low dilutions detach HeLa or KB cells from glass surfaces within a few hours after inoculation. A reproducible method for testing cell detachment was devised.

The factor present in infectious tissue culture fluids and responsible for cell detachment is trypsin-sensitive and non-dialyzable; it is smaller and more resistant to the effect of heat or ultraviolet light than the infectious virus particle.

Cell detachment activity was found to be temperature-dependent, and the cell-detaching titer of infectious tissue culture fluids was not affected by repeated exposure to HeLa cells. Inhibition of cell detachment by human or rabbit sera was observed only when other antibodies to adenovirus antigens were also present, but the antibody inhibiting cell detachment could not be correlated quantitatively with complement-fixing or homologous neutralizing antibody.
ELICITATION OF ALLERGIC CONTACT DERMATITIS IN THE GUINEA PIG
Authors: Eisen Herman N. , Tabachnick Milton
Published: June 2004

When one or two drops of a dilute, non-irritating solution of 2,4-dinitrochlorobenzene (DNCB) is applied to a small area of skin of the intact guinea pig, about 20 per cent of the applied material, or some derivative of it, is soon excreted in urine. In normal, as well as in specifically sensitized guinea pigs, DNCB at the site of local application becomes rapidly bound to skin protein through primary chemical bonds. Twenty-four hours after application roughly half of the material present at the local skin site is still extractable with organic solvents. Of the non-extractable dinitrophenyl groups, about 99 per cent are in epidermis, and about 85 per cent are substituted in ϵ-NH2 groups of lysine residues. Only traces of bound dinitrophenyl groups were observed in the corium. It is uncertain whether these are formed in situ, or are experimental contaminants, or are migratory epidermally formed conjugates. Even when DNCB is injected intradermally it combines predominantly with overlying epidermis and with epidermal components of hair follicles, but only slightly with corium.

The 2,4-dinitrophenyl conjugates which are localized in the deeper, viable half of the epidermis, close to the epidermal-dermal junction, are inferred to be the agents responsible for specifically evoking the allergic response in sensitized animals. Conjugates which are situated in the outer, cornified half of the epidermis are shown to be incapable of eliciting the allergic response. The results furnish a basis for interpreting a common pattern of lesions in allergic contact dermatitis as it occurs spontaneously in man.
THE ETIOLOGIC AGENTS OF VARICELLA AND HERPES ZOSTER
Authors: Weller Thomas H. , Witton Helen M. , Bell E. John
Published: June 2004

Fourteen strains of virus derived from the cutaneous lesions of cases of varicella and eight from patients with herpes zoster were propagated serially in primary explant cultures of human preputial or embryonic skin-muscle tissue. Infectious material could not be demonstrated in the fluid phase of infected cultures and inocula for passage therefore consisted of suspensions of infected tissue. Such tissue suspensions when stored in the frozen state did not regularly retain infectivity.

The cytopathic process was focal and appeared to develop as the result of transfer of infectious material from cell to contiguous cell. Optimum development of the focal lesions in vitro related directly to conditions favoring optimum tissue growth and was further influenced by the spatial relationship of the tissue outgrowth.

A variety of types of cells of human origin and several of monkey origin were susceptible to infection and responded with the formation of intranuclear inclusion bodies. The cellular response otherwise was variable, ranging from simple rounding with little change in size to the formation of large multinucleated cytoplasmic syncytia.

Strains of virus recovered from patients with varicella and from patients with herpes zoster could not be distinguished on the basis of their cultural attributes.
BACTERICIDAL ACTION OF HISTONE
Authors: Hirsch James G.
Published: June 2004

The arginine-rich fraction of calf thymus histone (histone B) exerts bactericidal activity on various coliform bacilli and micrococci under certain conditions in vitro. Final concentrations of less than 1 µg. histone per ml. kill susceptible microbes without detectable morphological alteration or lysis. Among the microorganisms highly susceptible to histone are Escherichia, Salmonella, Shigella, Pseudomonas, Klebsiella, and Micrococcus pyogenes var. albus. Less susceptible or completely resistant are Proteus, Serratia, Micrococcus pyogenes var. aureus, and various types of hemolytic streptococci.

Coliforms grown on solid media are much more resistant to the lethal effect of histone than are those cultured in liquid media. This difference is apparently related to the physiological state of the bacteria; agar grown microorganisms washed with water remain resistant to histone, whereas incubation in broth rapidly renders them more susceptible.

Histone is adsorbed onto heat-killed E. coli K-12 under conditions suitable for lethal action on this organism.

The bactericidal activity of histone is but little affected by pH of the test system, but ionic strength of the medium exerts a marked influence, the lethal action being reduced or blocked as the salt concentration reaches levels higher than that of 0.15–0.2 M NaCl. Relatively high concentrations of rabbit serum or of bovine plasma albumin reduce the bactericidal activity of histone in a medium at pH 7; these serum preparations are, however, essentially without effect in the test system at pH 5.6. The bactericidal effect of histone is antagonized by addition to the medium of small amounts of certain basic substances (protamine, spermine), or of various acid polysaccharides (heparin, nucleic acid, bacterial lipopolysaccharides).

The rate of killing of E. coli K-12 by histone increases as the temperature and the concentration of histone are raised. Within the limits studied, this rate also appears to be directly proportional to the concentration of bacteria in the system.
ELECTRON MICROSCOPY OF SERUM SICKNESS NEPHRITIS
Authors: Feldman Joseph D.
Published: June 2004

The renal lesions of serum sickness were studied with the electron microscope. The most prominent change was a marked swelling and proliferation of glomernlar endothelial cells causing obliteration of the capillary lumen. The basement membrane also showed focal thickenings and excrescences. Deposits of electron-dense material blended into the basement membrane. On the extracapillary side epithelial foot processes were reduced in number and replaced by broad sheets of cytoplasm which were closely applied to the basement membrane. From a comparison of electron and fluorescent microscopic studies of the glomerulus in serum sickness, it would seem that antigen-antibody complexes initiated injury in endothelial cells, although the possibility of the primary reaction occurring on basement membrane cannot be excluded.
AN EFFECT OF ANTIGEN-ANTIBODY INTERACTION ON BLOOD COAGULATION
Authors: Robbins John , Stetson Chandler A.
Published: June 2004

Each of several antigen-antibody systems studied has been found to affect the coagulation mechanism in the rabbit, causing a marked shortening of the coagulation time in vitro of samples of whole blood maintained in siliconized glassware. Addition of specific antigen to the blood of actively immunized animals or addition of antigen-antibody mixtures to the blood of normal animals produced the effect. The coagulation time of plasma was not affected, indicating that the phenomenon may be mediated by an effect on platelets. This effect of antigen-antibody interaction may be involved in the production of tissue damage in vivo.
RAPID INDUCTION OF MAMMARY CARCINOMA IN THE RAT AND THE INFLUENCE OF HORMONES ON THE TUMORS
Authors: Huggins Charles , Briziarelli Giuliano , Sutton Harold
Published: June 2004

A study was made of the optimal conditions for the induction of mammary cancer in the rat. 3-Methylcholanthrene was administered via the gastrointestinal tract, and a simple technique was worked out for inducing mammary cancer regularly and rapidly. Under conducive conditions, which were readily reproduced, multiple mammary carcinomas and these tumors only were induced in every rat in repeated experiments in 60 days or less. In the strain of animal employed in the present experiments, the rapid induction of mammary cancer proved to be a function of (a) dosage, (b) the timing of administration of the aromatic hydrocarbon, and (c) a favoring hormonal status of the recipient.

Most of the established tumors were hormone-dependent because they diminished markedly in size after hormone withdrawal through ovariectomy or hypophysectomy. Similar regression of the tumors was frequently achieved by the administration of dihydrotestosterone. Shrinkage of the cancers was accompanied by atrophic changes. Experimental mammary tumors with these physiologic characteristics have not been recognized hitherto.

The minority of mammary cancers continued to grow after ovariectomy; these are hormone-independent tumors and tumors of this sort had a characteristic cytologic appearance following modification of the endocrine state.

The cell population of a single tumor was not always uniform in its response to appropriate hormonal modifications. In certain tumors in response to changes in the endocrine status of the host many of the cells underwent atrophy whilst other adjacent cells in the same tumor continued to grow so that the net result was a hormone-independent tumor.

Hypophysectomy was the most effective method found to induce regression of mammary cancer in the present experiments.
IDENTIFICATION OF A TOXIC CELLULAR COMPONENT OF GROUP A STREPTOCOCCI AS A COMPLEX OF GROUP-SPECIFIC C POLYSACCHARIDE AND A PROTEIN
Authors: Schwab John H. , Cromartie William J. , Roberson Bob S.
Published: June 2004

The toxic cellular component of Group A streptococci, which produces a chronic multinodular lesion of the dermal connective tissue of rabbits, has been isolated by means of differential centrifugation and electrophoresis. The substance appeared to be a macromolecular complex of polysaccharide and protein, the polysaccharide having the serological and chemical characteristics of the group-specific C substance.

Evidence is presented indicating that the polysaccharide moiety is an essential part of the toxic complex. It is suggested that further studies of this material may help elucidate the mechanism of tissue damage in the non-suppurative sequelae of Group A streptococcal infections.
COMPARATIVE STUDIES ON THE PHYSICAL CHARACTERISTICS OF THE HERITABLE HAPTOGLOBIN GROUPS OF HUMAN SERUM
Authors: Bearn A. G. , Franklin E. C.
Published: June 2004

Ultracentrifugal studies of the α2-proteins of normal human serum before and after the addition of hemoglobin have revealed three separate and clearly distinguishable patterns based on the three major serum haptoglobin groups. Isolation of the three haptoglobin hemoglobin complexes disclosed characteristic patterns for each group. The heterozygote was found to possess electrophoretic and ultracentrifugal components not seen in either homozygote.

Separation of normal human serum, to which hemoglobin had been added, by conventional starch zone electrophoresis resulted in three characteristic patterns which also permitted the ready identification of the serum haptoglobin group. The haptoglobin hemoglobin complex from Group 1-1 had the fastest mobility and that of Group 2-2 the slowest. The heterozygote Group 2-1 had an intermediate mobility. Immunologic differences between the haptoglobin hemoglobin complexes of the three groups could not be detected.

Some of the variations in the reported electrophoretic and ultracentrifugal patterns of normal human serum could be reasonably ascribed to the group variation of the haptoglobins in man. The physical studies imply that the proteins characteristic of the heterozygote differ in size and charge from those present in either of the two homozygotes and indicate that the genetic control of the synthesis of the serum haptoglobins is probably exceedingly complex.
INTRACELLULAR LOCALIZATION OF TYPE 4 ADENOVIRUS
Authors: Denny Floyd W. , Ginsberg Harold S.
Published: June 2004

HeLa cells infected with types 1 or 4 adenovirus were separated into cytoplasmic and nuclear fractions by mechanical disruption and differential centrifugation and the quantity of infectious virus in each was determined. The results showed that the majority of infectious virus of both types could be isolated in the cytoplasmic fraction. It was not possible to explain the large amount of type 4 virus in the cytoplasmic fraction by the number of nuclei disrupted in the fractionation procedure, but the amount of type 1 virus in the cytoplasmic fraction could have been contributed by disrupted nuclei. This suggested that there might be a basic difference in the intracellular formation of the two types of virus. The intracellular distribution of complement-fixing antigen was similar to that of infectious virus in type 4-infected cells. Technical difficulties, inherent in cellular fractionation studies, were encountered but did not appear to explain the results obtained.
INTRACELLULAR LOCALIZATION OF TYPE 4 ADENOVIRUS
Authors: Boyer Georgiana S. , Denny Floyd W. , Ginsberg Harold S.
Published: June 2004

HeLa cell cultures infected with adenovirus type 4 were studied by light and phase-contrast microscopy and by the fluorescent antibody technique for visualization of intracellular antigen. The findings were correlated with the growth curve of infectious virus, determined from companion cultures. The results indicated that those cells undergoing characteristic structural changes observable by light microscopy were those which contain viral antigen. The distribution of the majority of the antigen within the infected cells corresponded to that of the regularly aligned granules and crystal-like masses seen in the nuclei of cells in stained and in unfixed cultures. The production of infectious virus was closely correlated with the development of the characteristic nuclear changes.
IN VITRO DIFFERENTIATION OF VIRULENT AND ATTENUATED POLIOVIRUSES BY THEIR GROWTH CHARACTERISTICS ON MS CELLS
Authors: Kanda Yukishige , Melnick Joseph L.
Published: June 2004

The MS character of polio-virus particles is described. Strains that produced relatively large plaques, up to 6 mm. in diameter, on a monkey stable (MS) cell line, were classified as MS+. Such strains were found to include the highly virulent poliovirus strains. Attenuated strains appeared deficient in this gene, for they produced tiny plaques less than 1 mm. in size, or no visible plaques at all; they were considered as MS mutants.

Strains of maximum neurovirulence for the monkey possessed the MS+ and d+ characters, while those of greatest attenuation were MS d. Strains possessing the MS d+ character showed high or intermediate attenuation.

Virulent strains grew equally well in MS or primary monkey kidney (MK) cells. Attenuated strains gave lower titers in MS cultures than in MK cultures. While MS cells after infection with a virulent virus yielded about 100 to 200 PFU per cell, only one PFU per MS cell was detected after infection with an attenuated virus.

A study of newly isolated Type 3 strains showed them to consist of the MS+d+ or MS d+ type. The MS+d+ virus proved to be highly paralytogenic for monkeys even by the intramuscular route, while the MS d+ virus was of the partially attenuated type.

The study of in vitro characters of viruses from children fed attenuated poliovirus offers a possibility for following genetic changes of the viruses after multiplication in the human enteric tract.
DEPLETION OF RESERVE PROTEIN FROM EXTRAVASCULAR EXTRACELLULAR FLUID
Authors: Yuile C. L. , Lucas F. V. , Neubecker R. D. , Cochrane C. G. , Whipple G. H.
Published: June 2004

During protein depletion produced by plasmapheresis and a very low protein diet there is a proportionately greater decrease in extravascular, extracellular fluid protein than in plasma protein.

A shift in the normal ratio of protein in these 2 compartments, approximately 1 to 1 in the dog, to over 2 to 1 as a result of depletion indicates an important, labile source of reserve protein for the plasma in the interstitial fluids.

This reserve source is limited since a maximum drop of 50 per cent in the total exchangeable pool and of 75 per cent in the extravascular, extracellular protein occurred after both shorter and longer periods of depletion. Under the rigid conditions of these experiments additional plasma protein removal was associated with loss of weight despite adequate caloric intake.

Investigation of the status of the interstitial fluid proteins in other conditions associated with disturbed protein metabolism seems warranted.
IMMUNOLOGICAL RELATIONSHIPS OF A FILTERABLE AGENT CAUSING A LEUKEMIA IN ADULT MICE
Authors: Friend Charlotte
Published: June 2004

The antigenic character of a filterable agent which induces leukemia in adult mice has been investigated. Mice and rabbits injected with filtrate yielded sera which specifically neutralized infectivity of the agent. Normal sera, sera from mice with other neoplasms—including leukemias from which no causative agent has as yet been obtained,—and sera from leukemic human beings contained no such neutralizing antibody. A formalinized vaccine prepared from filtrates of leukemic spleens induced a significant degree of immunity against the agent, approximately 80 per cent of the vaccinated mice being immune on challenge with it.
SEPARATION AND CHARACTERIZATION OF HUMAN SERUM CHYLOMICRONS
Authors: Scanu Angelo , Page Irvine H.
Published: June 2004

Chylomicrons were separated by low and high speed ultracentrifugation from lipemic sera of human subjects in the absorptive phase. The final chylomicron preparation was free from other serum components and contained a small constant amount of protein, approximately 2 per cent of the chylomicron fraction. Electrophoresis, immunochemical analysis, and absorption experiments identified the protein component as derived from a mixture of beta and alpha1 serum lipoproteins.

Large aliquots of an emulsion of serum freed of chylomicrons and coconut oil were incubated at 37°C. for 2 hours and ultracentrifuged as in the preparation of chylomicrons. The fat particles now showed the presence of minute amounts of beta and alpha1 serum lipoproteins in almost the same proportion as found in chylomicrons. "Finger prints" of delipidized samples of chylomicrons and particles from serum-coconut oil emulsion gave similar, although not identical patterns.

The data on "clearing factor" activity corroborated the finding that serum alpha1 lipoproteins are contained in chylomicrons and particles from serum-coconut oil emulsion. These two lipide particles, partially delipidized, were both able to activate a "clearing factor" system in vitro, a property exhibited only by intact or partially delipidized alpha1 serum lipoproteins. Clearing activity was satisfactorily determined by using an emulsion of coconut oil mixed in agar as a substrate to give an opaque gel, in which the diffusing enzyme showed its activity by areas of clearing. The results obtained by this technique were in agreement with those based on fall in optical density and non-esterified fatty acid production.

Chemical analysis of serum chylomicrons showed a concentration of cholesterol and phospholipides higher than could be accounted for by the attached beta and alpha1 serum lipoproteins.

On the basis of these results the assumption is made that in the blood stream small amounts of serum lipoproteins, by a process of adsorption, form a complex with the absorbed triglycerides, cholesterol, and phospholipides, to produce chylomicrons.
STUDIES ON TUBERCULIN FEVER
Authors: Hall Charles H. , Atkins Elisha
Published: June 2004

Evidence has been presented that the fever elicited by intravenous administration of old tuberculin (O.T.) in BCG-infected rabbits is a specific property of this hypersensitivity system and is probably not due to contamination of tuberculin with bacterial endotoxins. Daily injections of O.T. in sensitized animals resulted in a rapid tolerance to its pyrogenic effect. Tuberculin tolerance can be differentiated from that occurring with endotoxins and was invariably associated with the development of a negative skin test. The mechanism of this tolerance would thus appear to be desensitization.

A circulating pyrogen found during tuberculin fever was indistinguishable in its biologic effects from endogenous pyrogens obtained in several other types of experimental fever. This material produced fevers in normal recipients and therefore may be clearly differentiated from O.T. itself which was pyrogenic only to sensitized animals. Since the titer of serum pyrogen was directly proportional to the degree of fever induced by injection of O.T. in the donor animals, a causal relation is suggested.

On the basis of these findings, it is postulated that tuberculin fever is due to a circulating endogenous pyrogen released by a specific action of O.T. on sensitized cells of the host.
STUDIES OF MOUSE POLYOMA VIRUS INFECTION
Authors: Rowe Wallace P. , Hartley Janet W. , Estes John D. , Huebner Robert J.
Published: June 2004

Three procedures have been compared for usefulness in titration and detection of polyoma virus: production of cytopathic effect (CPE) in mouse embryo tissue culture, production of HI antibody after inoculation into weanling mice (MAP test), and production of tumors in suckling hamsters during a 3 to 5 week observation period. The tissue culture and mouse antibody production tests were generally comparable in sensitivity, reproducibility, and time required to obtain results. Titration by tumor production in suckling hamsters was not suitable for quantitation because of marked variation in susceptibility among animals.

Virus was detected in tissues of normal mice from spontaneously infected colonies by either production of CPE in mouse embryo tissue culture or by the MAP test; virus was found in organs of 15 (58 per cent) of 26 mice with antibody, and 2 (8 per cent) of 24 mice without antibody.
STUDIES OF MOUSE POLYOMA VIRUS INFECTION
Authors: Brodsky Isadore , Rowe Wallace P. , Hartley Janet W. , Lane William T.
Published: June 2004

Mouse polyoma virus was stored at 4° and –60°C. for 8 weeks without any loss in hemagglutination or infectivity titer; storage at 37° for 8 weeks reduced infectivity titer by approximately 2.5 log10 units. Repeated freezing and thawing of infectious tissue culture fluid had no effect on virus titer. The stability of the virus to storage for 1 week at 4°C. was unaffected by suspension of infected tissue culture fluid in saline, demineralized distilled water, or 5 per cent horse serum in Eagle's basal medium. Heating the virus for 30 minutes at 60°C. had no effect on infectivity and hemagglutination titers. Heating at 65°C. for 30 minutes produced a 3 log unit loss of infectivity and a 4-fold decline in HA titer, and heating at 70°C. for 30 minutes usually produced complete inactivation of infectivity and HA. The virus was resistant to ultraviolet irradiation; ultraviolet irradiation for 2 hours caused a 4 log unit decrease in infectivity titer without affecting the HA titer. The virus was resistant to exposure to 2 per cent phenol and 50 per cent ethyl alcohol but was inactivated by 100 per cent ethyl alcohol, and ethyl alcohol-iodine mixtures. Lyophilization had no effect on the stability of the virus.
THE CYTOTOXIC ACTION OF IMMUNE GAMMA GLOBULIN AND COMPLEMENT ON KREBS ASCITES TUMOR CELLS
Authors: Goldberg Burton , Green Howard
Published: June 2004

Electron microscopic studies of Krebs ascites tumor cells treated in vitro with rabbit immune gamma globulin revealed a distinctive alteration in the structure of the cellular surface membrane. The subsequent addition of complement to this system severely damaged the cytoplasmic matrix, mitochondria, and endoplasmic reticulum. This sequence of events provides a structural basis for the cytotoxic action of antibody and complement.
STUDIES ON THE FORMATION OF COLLAGEN
Authors: Gross Jerome
Published: June 2004

The skin of severely scorbutic guinea pigs which were losing weight contained no detectible neutral salt-extractible collagen.

Conditions of growth (weight gain) which actively induced the formation of neutral salt-extractible collagen in the skin of normal guinea pigs failed to do so in the animal with ascorbic acid deficiency.

No excess of non-collagenous proline was found in neutral salt extracts of scorbutic skin as compared with normal.

Fractionation of these extracts failed to reveal the presence of significant amounts of a soluble component containing unusual proportions of glycine and proline relative to hydroxyproline.

It is concluded that deficiency of ascorbic acid either interferes with the synthesis of new collagen in intact skin or causes its destruction and removal as rapidly as it is produced.