bluuebunny/crossref_metadata_2025 huggingface dataset:
A CELLULAR BASIS OF IMMUNITY IN EXPERIMENTAL BRUCELLA INFECTION
Authors: Holland John J. , Pickett M. J.
Published: June 2004

Brucella suis, Brucella abortus, and Brucella melitensis were shown by microscopic and cultural procedures to multiply extensively within normal rat, mouse, and guinea pig monocytes maintained in vitro in cell cultures for 3 days. Intracellular growth of brucellae had no observable toxic effects on most monocytes, although many of the cells became completely engorged with brucellae within 3 days. Non-smooth brucellae and strain 19 multiplied slowly within normal monocytes. In contrast, "immune" monocytes) i.e. those derived from animals previously infected with smooth brucellae, greatly restricted the intracellular growth of smooth and non-smooth brucellae and strain 19. Growth of smooth Brucella, within either normal or "immune" monocytes, was not influenced by addition of Brucella antiserum to the culture medium.

Desensitization of immunized guinea pigs did not diminish the refractory state of their monocytes. Cellular resistance did not develop when animals were vaccinated with heat-killed brucellae, though these animals did produce agglutinating antibody. Similarly, vaccination of animals with living, rough B. suis failed to induce a refractory state in their monocytes, even though the vaccinated animals developed delayed hypersensitivity to smooth Brucella antigen.

In vivo studies of Brucella survival in the spleens of normal and vaccinated mice (treated with streptomycin to prevent extracellular survival) gave strong support to the in vitro demonstrations of acquired "cellular immunity." Some implications of these results are discussed.
THE REMOVAL OF CARTILAGE MATRIX, IN VIVO, BY PAPAIN
Authors: McCluskey Robert T. , Thomas Lewis
Published: June 2004

The intravenous injection of crystalline papain into young rabbits results in depletion of cartilage matrix throughout the body, with loss of rigidity and collapse of the ears, provided the enzyme is inactivated by oxidation or sulfhydryl blocking agents prior to administration. Cysteine-activated crystalline papain, when injected intravenously, produces little or no change in cartilage.

The changes which occur in cartilage following an injection of inactivated crystalline papain are indistinguishable from those produced by crude papain.

Activation of crude papain by cysteine prior to injection results in loss of its capacity to produce in vivo changes in cartilage.

The progressive changes which take place in cartilage in vivo also occur in vitro in isolated rabbit ears removed shortly after an injection of crude papain or inactivated crystalline papain. In vitro ear collapse occurs rapidly at 37°C. and does not occur at 4°C. Collapse is enhanced by exposing the cartilage to cysteine and prevented by exposure to iodoacetamide or p-chloromercuribenzoate.

The direct action of crystalline papain on plates of normal cartilage, in vitro, results in the same gross and histological changes which were observed in vivo. The direct action is accelerated by cysteine and inhibited by iodoacetamide or p-chloromercuribenzoate.

The intravenous injection of iodoacetamide-treated bromelin produces the same in vivo changes in cartilage as papain. Untreated bromelin has no demonstrable effect on cartilage.

It is suggested that the reason for the failure of activated papain to enter cartilage, after being injected intravenously, is that it probably reacts with a substrate or substrates in the blood. Oxidized or otherwise inactivated papain, in contrast, is readily taken up by cartilage and there converted to its active form.
A COMPARISON OF HUMAN ANTISERA TO PURIFIED DIPHTHERIA TOXOID WITH ANTISERA TO OTHER PURIFIED ANTIGENS BY QUANTITATIVE PRECIPITIN AND GEL DIFFUSION TECHNIQUES
Authors: Finger Irving , Kabat Elvin A.
Published: June 2004

The limits of sensitivity of three gel diffusion methods are compared and their utilization in the detection of small amounts of antibody to antigens present in traces in a preparation is illustrated with the diphtheria toxin-human antitoxin system. The Preer modification of the Oakley-Fulthorpe technique and the Oudin tube method were found more sensitive than the Ouchteriony plate method, and permitted the detection of as little as 3 µg. antibody N/ml. of serum.

Antisera from eight Schick-negative individuals immunized with purified diphtheria toxoid have all been shown to contain, in addition to antitoxin, antibodies to substances present as impurities in the purified toxoid injected. The amounts of these antibodies in a serum and a partial characterization of their antigen-antibody curves have been determined through the combined use of quantitative precipitin and gel diffusion methods.

Different amounts of antibody have been precipitated by toxin and toxoid from individual sera. Evidence is presented that this may have been due to slight differences in antigenic specificity.

A serum, Hu, which had been held to contain no precipitating antibody, has now been shown, by the Preer and Oudin techniques, to contain at least 12 µg. of precipitating antibody N (per ml. serum) against an impurity in the toxoid preparation. This estimate has been confirmed by quantitative precipitin determinations. The presence of antibodies to impurities in all human antitoxins examined in the present work brings into question the assumption that human antitoxin as such has a skin-sensitizing capacity.
ACCESSORY PLASMA FACTORS INVOLVED IN THE BACTERICIDAL TEST FOR TYPE-SPECIFIC ANTIBODY TO GROUP A STREPTOCOCCI
Authors: Stollerman G. H. , Kantor F. S. , Gordon B. D.
Published: June 2004

The bloods of two apparently healthy human beings, of 25 studied, failed to produce a strong bactericidal test for type-specific antibody to the M protein of group A streptococci under in vitro conditions wherein most human blood leukocytes rapidly phagocytize and destroy virulent organisms in the presence of anti-M antibody and accessory plasma factors.

The defect in bactericidal activity of these two individuals is associated with the plasma rather than with the blood leukocytes. Leukocytes suspended in these atypical plasmas showed a characteristic delay in the rate of activation of phagocytosis.

Although previously the bloods of laboratory animals (except monkeys) had been reported to be much less active than human blood in this system, occasional exceptions were encountered in rabbits in this study. Two rabbits were found whose bloods were as strongly bactericidal against streptococci, in the presence of type-specific antibody, as the blood of the average "normal" human being.

The atypical behavior of some human and rabbit bloods in the bactericidal test may be explained by variations in accessory plasma factors that are as yet unidentified and that influence the rate of phagocytosis of virulent streptococci in vitro in the presence of type-specific antibody.
INFECTIVITY OF RIBONUCLEIC ACID FROM POLIOVIRUS IN HUMAN CELL MONOLAYERS
Authors: Alexander Hattie E. , Koch Gebhard , Mountain Isabel Morgan , Van Damme Olga
Published: June 2004

Ribonucleic acid prepared by the method of Gierer and Schramm from concentrated and partially purified types I and II polioviruses has been demonstrated to be infectious for HeLa and human amnion cells in monolayers. In areas of cytopathogenic action resulting from invasion of cells by RNA, intact poliovirus, of the type from which the RNA had been prepared, is present.

The infectivity of the RNA was completely inactivated by a 2 minute exposure to purified ribonuclease or to whole normal monkey serum shown to contain measurable concentrations of this enzyme. Whole virus infectivity was not influenced by RNAase or whole normal monkey serum. Normal and polio-immune globulin, desoxyribonuclease, lysozyme, proteolytic enzymes, and bovine albumin failed to inactivate the infectivity of RNA.

The degree of infectivity of isolated RNA from poliovirus for cells in monolayer was greatly influenced by the ionic strength of the environment.

The experimental evidence suggests that isolated poliovirus RNA is the carrier of the biological activity responsible for infection of cells and for transmission of genetic information which controls type specificity.
PAPAIN-INDUCED CHANGES IN RABBIT CARTILAGE
Authors: Tsaltas Theodore T.
Published: June 2004

Some biochemical aspects of the collapse of the rabbit ears produced by the intravenous injection of papain have been studied. A marked depletion of chondromucoprotein (M.C.S.) and a reduction of the S35 content of cartilage matrix were found to coincide with the gross and histologic changes in the cartilage. At the same time there was a marked increase in the amount of S35 in the serum and an increase of S35 and glucuronic acid excreted in the urine. Alteration in the composition of the M.C.S. remaining in the cartilage of the papain-injected animals was detected.

The findings indicate that the collapse of the rabbit ears is due to loss of chondromucoprotein from cartilage and reduction of chondroitin sulfate in the chondromucoprotein that remains.

All these changes were reversed in recovery.
AN ALTERNATIVE MECHANISM FOR THE PROPERDIN SYSTEM
Authors: Nelson Robert A.
Published: June 2004

Evidence is presented that phenomena ascribed to the properdin system may be explained in terms of classical antibody (Ab) in combination with three of the components of complement (C'), i.e., C'1, C'4, and C'2 respectively. The results suggest that the complex of properdin (P) with zymosan (Z) represents a mixture of Z·Ab, Z·Ab·C'1, 4, Z·Ab-C'1, 4, 2, and Z·Ab·C'1, 4, 2 in a decayed state.

The purported preferential reactivity of Z with the third component of C' (C'3) is not supported by the present experiments in which Z was reacted with C' in both guinea pig and human sera. Approximately the same number of reactive units of C'1, 4 and of C'3 were inactivated by Z, as well as by D. pneumoniae and a washed specific precipitate of bovine albumin-anti-albumin.

The latter evidence that small amounts of antigen-antibody complex fix significant amounts of C'3 stands in contrast with the classical concept that C'3 is not fixed in ordinary complement fixation reaction. The observed reactivity of C'3 is explained on the basis of the present use of essentially undiluted serum as a source of C'3 and of 37° as the temperature for fixation.

Ancillary data indicate that purified properdin contains Ab. In the presence of a chelating agent and at 0° properdin agglutinated Z granules. Measurements of nitrogen (N) uptake by Z suggest that 0.25 µg. N were contributed by solutions stated to contain 1 unit of properdin.

The broad spectrum of reactivity or cross-reactivity of the Ab in normal serum is likely due to the wide distribution in nature of closely related polysaccharides. Further immunochemical studies are necessary to establish definitively the origin and mode of action in "natural resistance" of antibodies reactive with these polysaccharides.
THE CUTANEOUS REACTION TO SOLUBLE ANTIGEN-ANTIBODY COMPLEXES
Authors: Cochrane Charles G. , Weigle William O.
Published: June 2004

The in vivo activity of soluble antigen-antibody complexes was tested by a single intradermal injection in rabbits. Skin reactions were obtained marked by erythema, induration, and occasionally hemorrhage and necrosis. Microscopically, diffuse inflammation and occasional vascular necrosis could be found at all dosages. This indicates that soluble antigen-antibody complexes are phlogogenic and provides support for the suggestion that complexes are responsible for the lesions seen in serum sickness.

The reactions were similar in severity to local passive Arthus (LPA) reactions at equal dosages of antibody in the dosage range studied.

BSA antigen could be found in large concentrations in affected vessel walls of both reverse passive Arthus (RPA) and active or classical Arthus reactions. It is suggested that this predominantly vascular localization of antigen might bring about the relative severity of the RPA and active Arthus reactions, as contrasted to the complex and LPA reactions.

The finding of affected vessels in the complex and LPA reactions containing little or no antigen and antibody, while these components were present in adjacent areas, suggests that the antigen-antibody combination may cause vascular reaction and damage by the release of physiologically active mediators from the tissue or tissue fluid.
EFFECTS OF ARSENIC-AZOPROTEINS ON MOUSE LYMPHOMA CELLS IN VIVO
Authors: Kidd John G.
Published: June 2004

Conjugates made by coupling diazotized arsanilic acid with one or another of a variety of proteins regularly brought about the complete regression of established 6C3HED lymphomas in living mice without perceptibly harming the latter, while untreated control animals regularly died with lymphomatosis. Histologic studies made plain that the lymphoma cells promptly die in mice treated with the arsenic-azoproteins, while those in untreated control animals continue to proliferate. Various inorganic and organic arsenicals (including arsanilic acid and 4-arsonophenyldiazotate) were essentially devoid of effect on the lymphoma cells in vivo, and this proved true as well of the proteins employed (serum albumins and globulins procured from several species, casein, and ovalbumin). Mixtures of arsanilic acid and the several proteins, various sulfur-azoproteins, and a number of other substances—viz., amethopterin, chlorambucil, 6-mercaptopurine, 8-azaguanine, azaserine, 6-azauracil, 5-fluorouracil, thioTEPA, and DON, each given in maximal tolerated amounts—also failed to influence notably the course of established 6C3HED lymphomas in vivo.

Although readily overcoming Lymphoma E9514 cells growing in the subcutaneous tissues of susceptible mice, the arsenic-azoproteins had little or no effect once these cells had reached the livers and spleens of susceptible hosts. Furthermore the arsenic-azoproteins had little or no effect in vivo on the cells of Lymphoma AKRL1, L1210, and L4946.

The findings were considered in relationship to the respective susceptibilities of several types of lymphoma cells to other anti-lymphoma agents—notably guinea pig serum, immune serums prepared in rabbits with mouse lymphoma cells as antigens, and a variety of chemical compounds. Taken together, the observations provide proof that lymphoma cells of various types, although resembling one another quite closely in growth characteristics following transplantation in susceptible hosts, and in morphology as disclosed by ordinary microscopy, differ notably in susceptibility to the effects of the several anti-lymphoma agents.
INACTIVATION OF ENDOTOXIN BY A HUMORAL COMPONENT
Authors: Skarnes Robert C. , Rosen Fred S. , Shear Murray J. , Landy Maurice
Published: June 2004

A humoral substance which inactivates endotoxin in vitro has been shown to be clearly distinguishable from complement, properdin, and specific antibody. For the present, it is designated "endotoxin-detoxifying component" or EDC.

Animal species could be grouped in three categories with regard to the EDC activity of their sera; rat serum was highly potent; chimpanzee, dog, horse, and guinea pig sera were much less active; mouse, rabbit, and sheep sera exhibited no activity. The EDC potency of human sera varied widely, ranging from high to barely discernible activity. In contrast to the variations of EDC potency in serum, citrated plasma from all species manifested high potency of about the same magnitude.

The influence of time, temperature, pH, and concentration of reactants on the inactivation of endotoxin by EDC was examined. EDC activity in plasma and serum was found to be labile to beating at 56°C. for 1 hour. Bacterial endotoxins, derived by different isolation procedures from smooth and rough Gram-negative species, varied considerably in susceptibility to EDC action.
COLICINE K
Authors: Amano Tsunehisa , Goebel Walther F. , Smidth Elizabeth Miller
Published: June 2004

By immunological means it has been shown that colicine K is associated with the O antigen of the colicinogenic bacillus E. coli K235 L+OC+.

The colicine K-O antigen complex elicits the formation of at least two types of antibodies, one a precipitin, the other a colicine-neutralizing antibody. The first precipitates colicine K without neutralizing it, the second neutralizes the colicine without precipitating it.

Unlike the purified colicine K complex, the colicine protein component of the O antigen is precipitable by the neutralizing antibody.

There is no demonstrable serological relationship between colicine K and phage T6. These two agents must be considered to be separate and distinct entities.
FOLINIC ACID AND NON-DIALYZABLE MATERIALS IN THE NUTRITION OF MALARIA PARASITES
Authors: Trager William
Published: June 2004

The extracellular survival of the malaria parasite Plasmodium lophurae was favored on the 4th day of incubation in vitro by the presence in the medium of added folinic acid at a concentration of about 5 µg. per ml. The development of the human malaria parasite P. falciparum intracellularly in suspensions of human erythrocytes was better in a medium with a high than in one with a low concentration of folic acid.

In the early extracellular development of P. lophurae in vitro erythrocyte extract could be partially replaced by certain yeast protein preparations and by a non-dialyzable fraction, free from hemoglobin, prepared from duck erythrocyte extract by means of starch electrophoresis.
AN INFECTIOUS CUTANEOUS FIBROMA OF THE VIRGINIA WHITE-TAILED DEER (ODOCOILEUS VIRGINIANUS)
Authors: Shope Richard E. , Mangold Robert , MacNamara Lester G. , Dumbell Keith R.
Published: June 2004

A naturally occurring cutaneous fibroma of deer has proven to be experimentally transmissible in deer. The causative agent is a virus that is readily alterable through Berkefeld N candles and that survives in fibroma tissue for at least as long as 27 months in glycerol-saline at –20°C. The experimentally produced deer fibroma has an incubation period of about 7 weeks, a very slow rate of growth, and a high regression rate.
AMINONUCLEOSIDE NEPHROSIS
Authors: Vernier Robert L. , Papermaster Benjamin W. , Good Robert A.
Published: June 2004

Experimental renal disease was produced in young rats by daily subcutaneous injections of 6-dimethylamino purine, 3-amino-d-ribose (aminonucleoside). The physiologic, biochemical, and light microscopic changes were similar to those observed in human nephrosis.

Electron microscopy of the glomeruli from animals which received seven or more daily injections of aminonucleoside revealed characteristic abnormalities of the epithelial cells of the glomerular capillaries. These changes consisted of swelling, coalescence, and eventual obliteration of the epithelial cell foot processes and an increase in the number and the size of epithelial cytoplasmic vacuoles. The serial development of the ultramicroscopic pathologic changes in the epithelial cells, as observed by study of animals through the course of the disease, indicated that the smudging of the foot processes occurred at the time of onset of severe proteinuria.

Further changes, consisting of hypercellularity due primarily to an increase in the number of endothelial cells and an increase in the amount of basement membrane-like material, were regularly observed by the 12th day after injections were begun. These abnormalities were correlated with the development of uremia in the later stages of the disease process.

The distal and proximal renal tubules were abnormal by the 7th day after injections were begun, and showed localized swelling between the cristae of the mitochondria and a decrease in over-all cytoplasmic density, described as hydropic change.

Electron microscopy of glomeruli from animals which had partially recovered from aminonucleoside nephrosis revealed areas of normal epithelial cell morphology. This observation was interpreted as evidence of partial reversal of the ultramicroscopic changes in the recovery phase of the disease.

These observations of the fine structure of pathologically altered glomeruli and tubules in aminonucleoside nephrosis are similar to our findings in human nephrosis as revealed by electron microscopy of serial renal biopsies.
THE PRECIPITIN REACTION BETWEEN DNA AND A SERUM FACTOR IN SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: Deicher H. R. G. , Holman H. R. , Kunkel H. G.
Published: June 2004

The sera of certain patients with systemic lupus erythematosus contain an antibody-like substance capable of reacting with highly purified DNA preparations from widely divergent sources. Precipitin reactions have been demonstrated by double diffusion in agar and quantitative precipitin curves have been obtained. Complement was observed to be fixed in the reaction.

Evidence was obtained that the serum factor possessed antigenic properties similar to those of γ-globulins and migrated with this fraction on zone electrophoresis. The interaction of this factor with DNA exhibited certain specific characteristics which differ considerably from non-specific reactions between DNA and proteins in general.

The DNA-precipitating factor appeared to be one of a number of related factors reacting with nuclear constituents of many different cells. It differed in certain respects from the "LE factor" which is responsible for the formation of "LE cells."

The accumulated evidence, although not yet conclusive, favors the concept that the precipitating factor represents an antibody to DNA, and that it is one of a number of autoantibodies elicited in this disease.
THE BIOLOGICAL ACTIVITY OF SOLUBLE ANTIGEN-ANTIBODY COMPLEXES
Authors: Ishizaka Kimishige , Ishizaka Teruko , Campbell Dan H.
Published: June 2004

Soluble BSA-anti-BSA complexes, formed in antigen excess, give immediate skin reactions in normal guinea pigs. The mechanism of the reaction is not that of passive or reversed passive anaphylaxis. The complex itself is toxic.

Skin activity of the complex depends on its composition. It has become obvious that the complex composed of two antigen molecules and one antibody molecule, (Ag2Ab), does not have the activity, whereas, Ag3Ab2 and more complicated complexes do.

The role of complement as well as speculation on the structural changes of antibody-antigen complexes is presented.
PLASMA PROTEIN TURNOVER AND TISSUE EXCHANGE
Authors: Yuile C. L. , Lucas F. V. , Olson J. P. , Shapiro A. B.
Published: June 2004

The rate of plasma protein turnover is more rapid in dogs receiving adequate dietary protein than when a diet devoid of protein is fed. Both albumin and combined globulins are involved in this change.

The difference in turnover is reflected in a total protein half-life of 4.8 days with protein feeding versus 7.8 days without protein in the diet and in the metabolism of 1.0 and 0.65 gm. per kilogram of body weight per day on the respective diets.

Additions of dietary protein from 10 to 30 per cent caused no further increase in the rate of plasma protein turnover.

With protein depletion due to plasmapheresis and a very low protein diet there is evidence of reduced protein metabolism as indicated by nitrogen retention as well as a reduction in total plasma protein breakdown and interchange of isotope between plasma and tissue proteins.

Following introduction of labeled plasma protein into the circulation the net amount of isotope transferred to tissues has been computed from the difference between total plasma protein breakdown and combined C14 excretion in urine and expired air. In animals receiving adequate dietary protein, tissue transfer amounts to 70 per cent of the total lost from the plasma proteins each day while the percentage rises to 85 in depleted dogs deprived of protein.

In dogs with both plasma and tissue proteins labeled it can be estimated that, under conditions of protein feeding, an amount of C14 approximately equal to that lost from the plasma must recycle to account for the observed decrease in Apparent plasma protein turnover rate, (t½ of 15 versus 5 days). Without protein in the diet the isotope contribution of the tissues to the maintenance of plasma protein levels must be as great as or greater than that transferred in the opposite direction.
THE RESPIRATION AND CYTOCHROME OXIDASE ACTIVITY OF RAT AORTA IN EXPERIMENTAL HYPERTENSION
Authors: Daly Marie M. , Gurpide E. Gambetta
Published: June 2004

Oxygen consumption and cytochrome oxidase activity of aortas of rats with experimental hypertension were found to be higher than the corresponding values for aortas of normotensive animals. The higher metabolic activity of aortas of hypertensive animals appeared to be due both to an increase in the proportion of muscle cells to connective tissue fibers and to a higher activity of the intracellular portion of the tissue.
THE CELLULAR TRANSFORMATION OF INJECTED COLLOIDAL IRON COMPLEXES INTO FERRITIN AND HEMOSIDERIN IN EXPERIMENTAL ANIMALS
Authors: Richter Goetz W.
Published: June 2004

As revealed by electron microscopy and electron diffraction, the physical state of ferric hydroxide micelles contained in iron-dextran, saccharated iron oxide, and hydrous ferric oxide ("ferric hydroxide") differs notably from the state of the ferric hydroxide in ferritin or hemosiderin. By virtue of this difference one can trace the intracellular transformation of colloidal iron, administered parenterally, into ferritin and hemosiderin.

One hour after intraperitoneal injection of iron-dextran or saccharated iron oxide into mice, characteristic deposits were present in splenic macrophages, in sinusoidal endothelial cells of spleen and liver, and in vascular endothelial cells of various renal capillaries. Four hours after injection, small numbers of ferritin molecules were identifiable about intracellular aggregates of injected iron compounds; and by the 6th day, ferritin was abundant in close proximity to deposits of injected iron compounds. The latter were frequently situated in cytoplasmic vesicles delimited by single membranes. These vesicles were most frequently found in tissue obtained during the first 6 days after injection; and in certain of the vesicles ferritin molecules surrounded closely packed aggregates of injected material. Much unchanged ferric hydroxide was still present in macrophages and vascular endothelial cells 3 to 4 weeks after injection.

While electron microscopy left no doubt about the identity of injected ferric hydroxide on the one hand, and of ferritin or hemosiderin on the other, histochemical tests for iron failed in this respect.

Precipitation of ferric hydroxide (hydrous ferric oxide) from stabilized colloidal dispersions of iron-dextran was brought about in vitro by incubation with minced mouse tissue (e.g. liver), but not by incubation with mouse serum or blood.

Subcutaneous injections of hydrous gel of ferric oxide into mice initially produced localized extracellular precipitates. Most of the material was still extracellular 16 days after injection, though part of it was phagocytized by macrophages near the site of injection; but apparently none reached the spleen in unaltered form. Five days after injection and thereafter, much ferritin was present in macrophages about the site of injection and in the spleen.

The findings show that iron preparations widely used in therapy can be identified within cells, and that their intracellular disposition and fate can be followed at the molecular level. Considered in the light of previous work, they indicate that the characteristic structure of the ferric hydroxide micelles in molecules of ferritin is specific, and develops during the union of apoferritin with ferric hydroxide. Apparently this union does not depend upon specific cell components.
THE RELATIVE IMPORTANCE OF THE CAPSULE AND THE M-ANTIGEN IN DETERMINING COLONY FORM OF GROUP A STREPTOCOCCI
Authors: Wilson Armine T.
Published: June 2004

Evidence is presented showing that the surface configuration of Group A streptococcal colonies depends largely on whether or not the cocci form a capsule. Strains which form capsules during growth on agar produce mucoid or matt colonies. Strains that do not form capsules during growth on agar produce glossy colonies. Whether or not M antigen is formed by the growing cocci appears to have no direct effect on surface configuration of the colony, although there is an indirect and partial association between M production and the mucoid-matt variant state and between M deficiency and the glossy variant state.
EXPERIMENTAL ATHEROSCLEROSIS AND CARDIAC INFARCTS IN RATS
Authors: Wilgram George F.
Published: June 2004

Marked obesity was induced in rats by feeding a high fat, egg yolk-rich diet. The obese rats were hyperlipemic and showed an increased incidence of lipomatous coronary lesions, but did not develop severe atheromatous lesions.

Spontaneous vascular lesions of several kinds have been observed in aging rats. Among them, plaques containing a fibrin-like material seem to be conspicuous. However, these lesions differ from the experimentally induced changes, which were more fatty. Atherosclerosis, as it is defined in human pathology, has not been observed to develop spontaneously in rats.

Experimental induction of marked hyperlipemia and hypercholesterolemia by feeding a high fat egg yolk-rich diet (supplemented with cholesterol, choleate, and thiouracil), and use of viosterol to cause vascular injury, led to severe atherosclerosis, coronary occlusion, and myocardial infarction.

A consideration of all the findings reported here leads to renewed support of the concept that atherosclerosis has a combination of causes (Aschoff, Anitschkow, Page). Of all the etiological factors considered here, elevation of blood lipides and vascular injury are thought to be the most important ones.
THE MAMMALIAN CELL-VIRUS RELATIONSHIP
Authors: McLaren Leroy C. , Holland John J. , Syverton Jerome T.
Published: June 2004

Primary or established strain cultures of a variety of primate cells that were susceptible to cytopathic infection strongly adsorbed poliovirus. Insusceptible non-primate cells in primary or established-strain culture did not so adsorb virus (or propagate it), with exception of the ERK-1 embryo rabbit kidney strain. All tested cells, regardless of type or susceptibility, adsorbed about 1 per cent of input virus, which became cell-associated (CAV) without loss of infectivity. In combination with susceptible or insusceptible cells, CAV was only about 90 per cent neutralized by homotypic antiserum. CAV eluted continuously from non-susceptible cells with continued incubation; eluted virus gave rise to infection and new CAV to the same degree in susceptible cells as did original virus.
STUDIES ON PRIMARY ATYPICAL PNEUMONIA
Authors: Liu Chien , Eaton Monroe D. , Heyl James T.
Published: June 2004

By using the indirect method of fluorescent staining to study the antibody response in patients with primary atypical pneumonai associated with the development of cold agglutinin, it was found that the PAP antibody developed during the 2nd and 3rd week of the illness, and persisted for over a year, and is not related to the cold and streptococcus MG agglutinins. The development of the PAP fluorescent staining antibody paralleled the neutralizing antibody for the PAP virus as tested in cotton rats. The sensitivity of this specific serological test was indicated by the observation that 67 to 92 per cent of the patients in several outbreaks of PAP showed a rise of antibody titer during convalescence. Absorption of the sera with various tissue powders did not affect the PAP antibody detected by this method.
PARATHYROID TRANSPLANTS IN RATS
Authors: Russell P. S. , Gittes R. F.
Published: June 2004

1. A reliable method of parathyroid grafting in rats, and of assessing the functional state of such grafts in terms of blood calcium has been devised.

2. Parathyroid homografts between rats of proven genetic diversity may be rejected as promptly as skin; but the majority survive for an indefinite period, there being no intermediate class.

3. Surviving parathyroid grafts in this genetically diverse combination invariably succumb in the presence of the immunity induced by a later skin graft from the same donor.

4. Parathyroid grafts between rats of less genetic diversity have usually responded to skin graft-induced immunity in the same manner as those between more dissimilar rats. The less divergent group, however, revealed an occasional persistent functioning of parathyroid grafts even in the face of the sensitivity incidental to an accelerated reaction to skin.

5. The hypothesis is presented that the parathyroid tissue of the rats studied was deficient in effective transplantation antigens as compared with those of their skin. This weakness in apparent antigenicity may be a reflection of a deficiency in production, availability, or content of antigens in the tissue transferred.
MOLECULAR GROWTH REQUIREMENTS OF SINGLE MAMMALIAN CELLS
Authors: Fisher Harold W. , Puck Theodore T. , Sato Gordon
Published: June 2004

Two purified serum protein fractions, fetuin and serum albumin, will replace whole or dialyzed serum in supporting the growth of single S3 HeLa cells in an otherwise chemically defined nutrient solution.

In the serum-free medium, single S3 cells will form macroscopic colonies with essentially 100 per cent efficiency.

The generation time of S3 cells in the serum-free medium is approximately 50 per cent greater than that observed in an optimal, serum-containing medium.

All components of the serum-free medium are available commercially, except fetuin, which can easily be prepared in substantial quantities.

The problem of the purity of the protein preparations and of their possible roles in promoting cell growth is discussed.
ISOTONICITY OF LIVER AND OF KIDNEY TISSUE IN SOLUTIONS OF ELECTROLYTES
Authors: Opie Eugene L.
Published: June 2004

Solutions of a wide variety of electrolytes, isotonic with liver or with kidney tissue, have approximately the same osmotic pressure as solutions of sodium chloride isotonic with tissues of the two organs respectively; that is, with solutions approximately twice as concentrated as the sodium chloride of mammalian blood plasma.

The molar concentration of various electrolytes isotonic with liver or with kidney tissue immediately after its removal from the body is determined by the molecular weight, valency, and ion-dissociation of these electrolytes in accordance with the well known conditions of osmosis.

The plasma membranes of liver and of kidney cells are imperfectly semipermeable to electrolytes, and those that enter the cell, though retarded in so doing, bring about injury which increases permeability to water.

The osmotic activity of cells of mammalian liver and kidney immediately after their removal from the body resembles that of plant cells, egg cells of marine invertebrates, and mammalian red blood corpuscles and presumably represents a basic property of living cells by which osmotic pressure may be adjusted to functional need.
STUDIES ON THE IMMUNOCHEMISTRY OF HUMAN LOW DENSITY LIPOPROTEINS UTILIZING AN HEMAGGLUTINATION TECHNIQUE
Authors: Briner William W. , Riddle Jackson W. , Cornwell David G.
Published: June 2004

Hemagglutination is a specific and sensitive technique for investigating the purity of lipoproteins and the immunologic relationships between low density lipoprotein fractions.

The Sf 10–400 and Sf 3–9 lipoprotein fractions, isolated from human serum by dextran sulfate-density gradient centrifugation procedure and repurified by centrifugation appeared to contain only lipoprotein antigens since these fractions did not stimulate the production of antibodies against other serum proteins. Cross-absorption experiments with lipoproteins carried on "tanned" cells demonstrated that the Sf 3–9 lipoprotein fraction contains all the antigenic components of the Sf 10–400 lipoprotein fraction together with additional antigenic components not found in the Sf 10–400 lipoprotein fraction. Thus Sf 3–9 and Sf 10–400 lipoprotein fractions are immunologically similar but not identical. Low density lipoproteins contain no antigens in common with the high density lipoproteins.

An Sf 3–9 antiserum can be used to detect both Sf 3–9 and Sf 10–400 antigens. The Sf 3–9 lipoprotein fraction used as an antigen will detect antibodies against both Sf 3–9 and Sf 10–400 lipoprotein fractions. The Sf 3–9 and Sf 10–400 antisera did not contain immune antibodies against erythrocytes of the different blood groups or against sheep, guinea pig, dog, calf, pig, horse, and chicken erythrocytes.

Normal subjects and subjects with recent myocardial infarctions had no circulating autoantibodies against the Sf 3–9 and Sf 10–400 lipoprotein fractions.
INTRACELLULAR SURVIVAL OF STAPHYLOCOCCI
Authors: Kapral Frank A. , Shayegani Mehdi Gh.
Published: June 2004

A tissue culture procedure is described which permits the quantitative evaluation of the intracellular survival of staphylococci within leucocytes. Staphylococcus aureus survived, but did not multiply, within neutrophils and monocytes of normal rabbits. The same was true of normal human blood leucocytes. Staphylococcus albus on the other hand was destroyed by these cells under the same conditions. Rat monocytes destroyed S. aureus and S. albus with equal facility. Although most experiments were carried out in the presence of 50 µg. streptomycin/ml., similar results were obtained without the use of this antibiotic.

The applications of the tissue culture procedure with regard to studies on virulence and immunity in staphylococcal disease are discussed.
THE NATURE OF THE IMMUNOLOGIC INADEQUACY OF NEONATAL RABBITS
Authors: Dixon Frank J. , Weigle William O.
Published: June 2004

It has been shown that cells from neonatal rabbits are capable of producing considerable amounts of antibody after exposure to antigen in vitro and transfer to x-radiated adult recipients. This suggests that the immunological inadequacy of these neonates is not dependent primarily upon the lack of cells capable of antibody formation.

Both in vitro sensitized neonatal lymphoid cells and in vivo sensitized adult lymphoid cells made much more antibody after transfer to x-rayed adult recipients than to neonatal recipients. Possible reasons for and significance of these observations are pointed out in the discussion.
THE MAMMALIAN CELL VIRUS RELATIONSHIP
Authors: Holland John J. , McLaren Leroy C. , Syverton Jerome T.
Published: June 2004

Ribonucleic acid extracted with phenol from Type 1 poliovirus, Coxsackie A-9, Coxsackie B-1, and ECHO 8 viruses infected non-primate cells and animals insusceptible to whole virus as such. Viral RNA was proved infectious for insusceptible cells in test systems of established cell lines, primary monolayer cultures, Maitland type cultures, and living animals inoculated intracerebrally. Cells of rabbit, swine, mouse, guinea pig, chicken, and hamster were infected. Each virus produced was identical with the virus donating RNA, in (a) neutralization by homotypic antiserum, (b) resistance to ribonuclease treatment, and (c) failure to be adsorbed or replicated by nonprimate cells, even of the strain producing the virus from RNA. Produced virus was adsorbed and replicated by susceptible primate cells as usual. Virus in RNA-infected cell cultures was produced in a single cycle unaccompanied by overt cytopathic effect on non-primate cells or disease of intracerebrally inoculated animals.

By drastic elution of infective poliovirus associated with rabbit cells exposed to massive inocula of intact virus, intact poliovirus was shown to infect insusceptible non-primate cells to produce progeny indistinguishable from the parent virus population. Under these conditions, infection was accomplished by about 10 virus plaque-forming units per billion inoculated.
SOME PHYSIOPATHOLOGICAL PARAMETERS OF NATURAL RESISTANCE TO INFECTION IN MURINE SALMONELLOSIS
Authors: Böhme Diethelm H. , Schneider Howard A. , Lee Johanna M.
Published: June 2004

Susceptible (BSVS) and resistant (BRVR) mice were experimentally infected with Salmonella typhimurium. The double strain inoculation technique was used in which both avirulent and virulent representatives of S. typhimurium were admitted into the hosts. The BSVS mice succumbed without exception while the BRVR mice survived to 52 per cent. No deaths occurred during the experimental period in non-infected control mice.

Parallel to the survivorship test, and concurrent with it, the activity of the reticulo-endothelial system (RES) was measured at frequent intervals in identically infected BSVS and BRVR mice and in their non-infected controls. For this measurement the carbon clearance method was used. No pre-infection difference of activity of the RES could be discerned in susceptible BSVS mice vs. resistant BRVR. Following infection, increases in the RES activity were detected in about the same magnitude in both mouse stocks. However, a difference was found in the time of onset. The susceptible animals showed an early and short increase in the activity of the RES, followed by a drop to control levels at the time of death. The resistant group exhibited a considerably delayed, but significant increase in RES activity, which returned to control levels approximately 4 weeks after infection.

The absolute white blood count did not undergo significant change in either of the two infected groups, but the susceptible animals showed a relative increase of their neutrophils at the expense of their lymphocytes.

Extensive anatomical changes were observed in both mouse strains, mainly confined to liver and spleen. These consisted of stasis, swelling of Kupffer cells, necrotic foci, histiocytic-monocytic nodules, widespread thrombosis of branches of the portal and splenic veins, and extensive areas of necrosis. These changes appeared earlier in susceptible than in resistant animals.

The implications of these findings are discussed.
STUDIES ON THE MECHANISM OF HYPERSENSITIVITY PHENOMENA
Authors: Osler Abraham G. , Randall Harry G. , Hill Betsy M. , Ovary Zoltan
Published: June 2004

The interaction of fresh rat and guinea pig serum with washed preformed immune aggregates has been studied with respect to the loss in hemolytic potency of the serum, diminution of the C'3; activity, and appearance of anaphylatoxin.

It has been found that the formation of anaphylatoxin, as judged by its effect on capillary permeability and smooth muscle contraction, is coincident with or subsequent to the fixation of all the known C' components.

Less anaphylatoxin is formed by aggregates formed with excess antigen than those in equivalence ratio combination.

C' fixation, as well as anaphylatoxin production, may be inhibited by chelation of the divalent cations, presumably by interfering with the fixation of C'1, C'4, and C'2.

Phlorizin suppresses the utilization of C'3 in immune hemolysis, C' fixation by antigen-antibody aggregates, and the production of anaphylatoxin. The biological activities associated with the fixation of C' are not manifest unless C'3 participates in this process at 37°C. It is concluded that the formation of anaphylatoxin may be regarded as a product of C' fixation.
ANALYSIS OF THE PROTEINS OF RAT SERUM BY STARCH ELECTROPHORESIS AND BY CATIONIC DETERGENT ANALYSIS
Authors: Jacox Ralph F.
Published: June 2004

A protein of unusual characteristics has been identified in normal rat sera by electrophoretic separation at pH 8.6, followed by precipitation of each fraction with a cationic detergent. This protein, which is closely identified with albumin after electrophoresis at pH 8.6, precipitates with cationic detergent at a low pH in contrast to albumin which precipitates with detergent only at a high pH. This protein has characteristics of a globulin and is designated as a "fast alpha fraction."

This fraction and albumin are present in about equal amounts in sera of normal rats. A separation of the fast alpha fraction can be made by electrophoresis in an acetate buffer of pH 4.25 and by precipitation according to a modified Cohn, cold-alcohol technique.

A protein of similar characteristics has not been found in either human or rabbit sera studied by the same method of electrophoresis and subsequent sub-fractionation with cationic detergent.
STUDIES ON THE PATHOGENESIS OF RABIES IN INSECTIVOROUS BATS
Authors: Sulkin S. Edward , Krutzsch Philip H. , Allen Rae , Wallis Craig
Published: June 2004

Studies on the pathogenesis of rabies in two species of experimentally infected insectivorous Chiroptera, the Mexican free-tailed bat (Tadarida mexicana), a quasi hibernator, and the little brown bat (Myotis lucifugus), a deep hibernator, provided evidence that brown adipose tissue may serve as an extraneural site for storage and multiplication of rabies virus. Although the Mexican free-tailed bat proved to be relatively insusceptible to experimental rabies infection, virus was demonstrated in the brown fat of 22 per cent of those animals shown to be infected by viral assay in white Swiss mice. Rabies infection in this species was most evident 20 to 40 days after intramuscular inoculation of virus. Rabies virus was found to be widely distributed in the little brown myotis 9 to 26 days following inoculation and virus concentrations in some of the tissues approached the level of the stock mouse brain virus suspension used in inoculating these bats. The shorter incubation period and higher virus titers in the tissues assayed reflect the increased susceptibility of Myotis lucifugus as compared with the Mexican free-tailed bat. Virus was demonstrated in the brown fat of 30 per cent of the experimentally infected Myotis.

In the experimentally infected Myotis lucifugus and in the Syrian hamster which is highly susceptible to rabies infection, rabies virus was isolated more frequently from the brown fat than from the salivary gland indicating that in a susceptible host brown adipose tissue may be as frequent a site of viral proliferation as salivary gland.

Since rabies virus was found to persist for long periods of time in the brown fat of experimentally infected bats and was occasionally demonstrated in this tissue alone, it is suggested that brown adipose tissue provides a mechanism by which these animals may serve as reservoirs for this agent in nature. The possibility that similar mechanisms may be involved in the maintenance of other viral agents during interepidemic periods is discussed.
EFFECTS OF BACTERIAL ENDOTOXIN ON METABOLISM
Authors: Berry L. Joe , Smythe Dorothy S. , Young Leona G.
Published: June 2004

Mice of different strains were protected against the lethal effect of bacterial endotoxin by concurrent injections of cortisone. Either inadequate amounts of cortisone or excessive quantities of endotoxin voided the protection.

Analyses of blood sugar, liver glycogen, muscle glycogen, and total body carbohydrate in the skinned eviscerated carcass were carried out on different strains of mice given endotoxin and/or cortisone. Poisoned animals were virtually depleted of all carbohydrate while mice given cortisone alone had concentrations of carbohydrate from three to four times that of normal mice. Mice given a lethal amount of endotoxin and a protective dose of cortisone had two to three times as much carbohydrate as animals injected with the same amount of endotoxin alone but significantly less than that found in normal mice.

Dibenzyline failed to alter the lethal effect of endotoxin and to reduce the carbohydrate loss that accompanied endotoxin administration.

Endotoxin, at the dosage level employed, lowered the temperature of mice 2°–3°C. during the first hour or two postinjection and the temperature remained essentially unaltered during the next 4 to 5 hours. Loss in body carbohydrate in endotoxin-poisoned mice cannot be explained, therefore, as the result of an elevated metabolic rate accompanying hyperthermia.

Endotoxin prevented the conversion of injected glucose into liver glycogen but not into muscle glycogen.

Mouse liver mitochondria, in the presence of endotoxin, released from ATP approximately the same amount of inorganic phosphate as that released in the presence of dinitrophenol.