bluuebunny/crossref_metadata_2025 huggingface dataset:
GLOMERULAR LESIONS AND THE NEPHROTIC SYNDROME IN RABBITS GIVEN SACCHARATED IRON OXIDE INTRAVENOUSLY
Authors: Ellis John T.
Published: June 2004

Intravascular precipitates, comprised at least in part of iron, formed regularly in rabbits given one or more injections of a saccharated iron oxide preparation intravenously, and these lodged in numerous capillaries throughout the body, particularly those of the lungs and kidneys. Large numbers of the brownish precipitates remained in the capillaries of the renal glomeruli during the first few days following injection of the iron, but most of them disappeared after 5 to 7 days, with only moderate amounts of brown pigment remaining in the endothelial cells of the renal glomeruli. Signs of acute injury of the glomerular tufts—namely) pyknosis of some of the endothelial cells, margination of leukocytes within the glomerular capillaries, and slight proliferation of the epithelial cells—also developed some 5 to 7 days following injection of the iron, along with marked proteinuria, which proved transitory if no further injections were given. When the iron preparation was given repeatedly over prolonged intervals, however, the proteinuria persisted and became extreme, and hypoproteinemia developed, often with hypercholesterolemia and transitory edema as well. Histological studies of the kidneys of rabbits manifesting the nephrotic syndrome, as just described, disclosed that virtually all the renal glomeruli were greatly altered, mainly owing to proliferation of the epithelial cells, together with some fibrosis and atrophy. Some of the rabbits having marked proteinuria and other functional changes eventually developed azotemia following repeated injections of the iron, and several of them lost weight and died; the renal glomeruli of these animals showed changes like those just described, but the alterations were more extensive.

Considered together, the findings provide evidence that the intravascular precipitates first occluded the glomerular capillaries for a period of several days following injection of the iron and then largely disappeared from them just prior to the development of morphologic signs of glomerular injury and proteinuria. Hence the possibility was considered that the intracapillary precipitates might have produced acute injury to the walls of the glomerular capllaries through the agency of anoxia. But it is plain that the findings of the present study do not disclose the essential nature of the anatomical change responsible for the proteinuria, or the means whereby this was produced.

The findings as a whole were briefly considered in relation to the pathogenesis of the nephrotic syndrome as it occurs naturally in human beings.
THE KINETICS OF IRON METABOLISM IN NORMAL GROWING SWINE
Authors: Jensen W. N. , Bush J. A. , Ashenbrucker Helen , Cartwright G. E. , Wintrobe M. M.
Published: June 2004

Plasma and red cell iron turnover rates were determined in 18 normal growing swine by the use of tracer doses of Fe59. Body surface counting was performed on a representative group of animals following the injection of the isotope.

The mean half-time of plasma iron disappearance was 1.19 ± 0.26 hours. Two exponential rates of disappearance of Fe59 from the plasma were observed in 15 of the pigs and a single rate was observed in the other 3. The mean plasma iron turnover rate was 1.11 ± 0.34 mg./kg. day. The average maximum incorporation of Fe59 into the erythrocytes was 92 ± 9 per cent. The mean red cell iron incorporation rate was 1.10 mg./kg. day, but an average of 0.42 mg./kg. day of this was calculated as being due to increasing red cell mass incidental to body growth, so that the true mean red cell iron turnover rate was 0.59 ± 0.19 mg./kg. day. The average "apparent" red cell life span was 63 ± 16 days. This is in agreement with the red cell life span of 62 days determined previously with glycine-2-C14.
CHANGES IN THE OSMOTIC ACTIVITY OF LIVER AND OF KIDNEY TISSUE CAUSED BY PASSAGE OF SODIUM CHLORIDE, UREA, AND SOME OTHER SUBSTANCES INTO CELLS
Authors: Opie Eugene L.
Published: June 2004

The osmotic activity of liver tissue and of kidney cortex tested within 10 minutes after immersion in solutions of sodium chloride has been increased by procedures which introduce sodium chloride, urea or creatinin into the body in excess of its elimination.

A substance formed by cell metabolism, namely urea, can increase the osmotic activity of liver and of kidney cells.

The amino acids, glycine and arginine, under similar conditions have not increased the osmotic activity of liver or of kidney cortex.
EFFECTS OF HORMONES ON THE ADRENAL NECROSIS PRODUCED BY BESNOITIA JELLISONI IN GOLDEN HAMSTERS
Authors: Frenkel J. K.
Published: June 2004

Adrenal necrosis has been described in golden hamsters where it occurs during the course of infection with Besnoilia jellisoni. This necrosis results directly from the active intracellular proliferation by this obligate intracellular protozoan organism.

After infection, adrenal necrosis is rarely observed in hypophysectomized hamsters. In unoperated animals adrenal necrosis is suppressed to varying degrees by cortisone (E), hydrocortisone (F), corticosterone (B), 11-dehydrocorticosterone (A), and possibly by 11-desoxycorticosterone (DOCA).

Besnoitia organisms proliferate in otherwise "immune" hamsters around the subcutaneous deposits of the acetates of cortisone (E), hydrocortisone (F), and 11-dehydrocorticosterone (A); a marked depression of general immunity follows the administration of pharmacologic doses of the former two hormones. Organisms do not proliferate around the sites of corticosterone acetate (B) and 11desoxycorticosterone acetate (DOCA) injection, nor next to deposits of testosterone propionate, 11-desoxy-17-hydroxycorticosterone acetate (Reichstein's compound S) and epinephrine in oil.

It is postulated that certain glucocorticoids can so modify immunity mechanisms locally, that general immunity becomes ineffective; this occurs in the adrenal glands owing to endogenous corticoid production, at the sites of exogenous corticoid injection, and proximal to that in the lungs.

A comparison is made with the pathogenesis of tuberculosis and histoplasmosis of the adrenal gland which results in Addison's disease in man, and it is concluded that a similar pathogenetic mechanism is operative. The use of glucocorticoids for replacement therapy is discussed in reference to their relative resistance-depressing activities in pharmacologic doses. These undesirable side effects would appear to be less pronounced, if not absent, if corticosterone (B) rather than cortisone (E) and hydrocortisone (F) therapy were used.

Porcine adrenocorticotrophic hormone (ACTH) appearsto depress the incidence of adrenal necrosis in unoperated hamsters, and supports proliferation of organisms in the adrenal cortex with subsequent necrosis in only a small proportion of hypophysectomized hamsters. The possibility is discussed that ACTH from a different species (hog) might lead to a change in the secretory activity of the hamster adrenal gland.
DOES THE INGESTION OF ALCOHOL INFLUENCE THE DEVELOPMENT OF ARTERIOSCLEROSIS IN FOWLS?
Authors: Nichols C. W. , Siperstein M. D. , Gaffey W. , Lindsay Stuart , Chaikoff I. L.
Published: June 2004

The effect of alcohol ingestion upon the development of naturally occurring and stilbestrol-induced arteriosclerosis was studied in the domestic fowl. In two experiments, a 15 per cent ethyl alcohol solution was used for drinking purposes, and in a third experiment wine containing 12 per cent of it was administered. The caloric intake of both food and alcohol was carefully controlled by pair-feeding, a glucose solution being used for drinking purposes to equalize the caloric intakes of the control birds with those of the alcohol-treated birds. A total of 224 cockrels was studied, and the period of observation for each experiment lasted 12 months.

The degree of arteriosclerosis in the thoracic and abdominal aortas was determined in the gross and microscopically, and the degree of lipide infiltration was determined microscopically. The gross grading of arteriosclerotic lesions agreed closely with the microscopic analysis of intimal thickening and lipide infiltration of the arterial wall.

The gross gradings were subjected to a critical statistical analysis which allowed precise statements to be made on the probability that a real effect would be overlooked. This analysis yielded no evidence that alcohol or the wine used had affected the degree of gross arteriosclerosis or lipide infiltration.
STUDIES ON NON-PRECIPITATING ANTIBODY
Authors: Sternberger Ludwig A. , Feinberg Samuel M. , Clarke Martha E.
Published: June 2004

Brief exposure of serum to alkali in the cold seems to convert non-precipitating antibody to a precipitin-like material. This was disclosed by the following lines of evidence.

1. Immune sera, after addition of antigen and removal of the ensuing precipitates, yielded after alkali treatment more antibody-antigen complex than did sera to which no antigen was added.

2. When immune sera were depleted of precipitating antibody, treated by alkali, and antibody-antigen complex was allowed to precipitate, the resulting supernates formed additional prescipitates upon admixture of specific antigen. No precipitation occurred upon addition of non-specific protein to the treated supemates or the addition of specific antigen to depleted sera not treated by alkali.

3. Alkali-treated immune sera precipitated more antigen than untreated sera.
TRANSFORMATION REACTIONS WITH TWO NON-ALLELIC R MUTANTS OF THE SAME STRAIN OF PNEUMOCOCCUS TYPE VIII
Authors: Macleod Colin M. , Krauss Marjorie R.
Published: June 2004

Two distinct R mutants of pneumococcus type VIIIS have been described in which the mutations leading to loss of type VIII polysaccharide production are non-allelic. A DNA extract prepared from either R strain restores the capacity to produce type VIII polysaccharide in the other strain. Autologous extracts are inert in this respect.

DNA extracts from pneumococcus type IIS when applied to the two R mutants consistently yielded a high proportion of cells transformed to type VIIIS and relatively small numbers of type IIS cells.

When extracts prepared from other encapsulated pneumococci, types IS, VIIS, XIVS, and XVIIIS, were applied to R mutant VIII-R1, a mixture of type VIIIS cells and cells corresponding to the type of the donor appeared, although the proportion of type VIIIS cells was not uniformly in excess. The same extracts applied to the second R mutant, VIII-R13, yielded transformed cells of the type of the donor only, or else transformation did not occur.

Transforming extracts of a strain of pneumococcus type IIIS gave rise only to type IIIS pneumococci when applied to either strain. Type VIIIS pneumococci were never recovered from such interactions.
A STUDY OF PLASMA PROTEIN ALTERATIONS IN RABBITS INFECTED WITH TYPE I PNEUMOCOCCI
Authors: Jacox Ralph F. , Feldmahn Alexandra
Published: June 2004

An investigation of the plasma protein changes in rabbits infected intradermally with Type I pneumococci has been carried out, utilizing a cationic detergent method of protein fractionation. A consistent pattern of change was observed. There was an increase in the alpha globulins and fibrinogen concentration which reached maximal levels at the height of the infection. Albumin fell to a minimal concentration when the increment of alpha globulins and fibrinogen was greatest. The beta-gamma concentration showed a significant decrease during the most severe phase of the infection but returned to normal several days after spontaneous subsidence of bacteremia.

The magnitude of these plasma protein alterations depended on the severity of the infection and the response of the host. Significantly greater changes were observed in rabbits severely bacteremic than in those with mild bacteremia. Administration of penicillin suppressed the infection and decreased the usual plasma protein alterations. Injection of cortisone prior to the onset of the Type I pneumococcus infection caused an early inhibition of the expected plasma protein changes, but later the protein pattem developed in the same manner as it did in the severely infected animals.
LATENT VIRAL INFECTION OF CELLS IN TISSUE CULTURE
Authors: Johnson Karl M. , Morgan Herbert R.
Published: June 2004

When chick embryo tissues cultivated for 13 days in Hanks's balanced salt solution (BSS) were infected with psittacosis virus (6BC), they did not support active viral multiplication until synthetic medium 199 of Parker (3) was added. By testing various combinations of the substances in this and other synthetic media, it was found that the minimum number of compounds required to effectively stimulate virus growth in the presence of BSS comprised the amino acids and water-soluble vitamins found in medium 199. Addition of either amino acids or water-soluble vitamins alone to BSS resulted in only slight stimulation of viral proliferation.

Many constituents of the synthetic media were found not to be essential to the stimulation of viral multiplication. The following substances added to a medium containing amino acids and water-soluble vitamins in BSS failed to increase the quantity of virus produced: diphosphopyridine nucleotide (DPN), triphosphopyridine nucleotide (TPN), coenzyme A, the fat-soluble vitamins, ribose sugars, and three biological reducing agents: cysteine, glutathione, and ascorbic acid. Among other substances that proved to be not essential a group of purines and pyrimidines present in medium 199 were found to be probably toxic to cells in the concentrations used, since virus titers were lower in media containing these compounds than in those from which they were absent.

A change in the nutritional status of these cells involving amino acids and water-soluble vitamins has thus permitted to transform a latent, undetectable viral infection to an inactive infection in vitro.
STUDIES ON THE INTERACTION BETWEEN PHAGOCYTES AND TUBERCLE BACILLI
Authors: Stähelin Hartmann , Suter Emanuel , Karnovsky Manfred L.
Published: June 2004

As a basis for studies on the interaction of phagocytes and tubercle bacilli experiments were carried out to obtain information on some biochemical characteristics of exudate leucocytes from guinea pigs.

It was found that total cellular phosphorus was the most suitable measure of protoplasm. Cell counts were less reliable because of unavoidable clumping in the suspension, and dry weight measurements were less specific when contamination with erythrocytes occurred. The utility of phosphorus measurements in this connection depends upon the fact that an erythrocyte contains only 4 per cent of the phosphorus present in a leucocyte.

From measurements on mixed suspensions consisting of varying known proportions of polymorphonuclear and mononuclear leucocytes as determined by differential counting, it was possible to compute true values for these two cell types with respect to oxygen consumption and lactic acid production. Thus it was found that monocytes consumed considerably more oxygen and produced more lactate than polymorphonuclear leucocytes. From the data obtained it is suggested that differences in metabolic activity found when comparing cell suspensions obtained by the use of different irritants are due to different proportions of the two cell types.

In particular, the effects of oxygen tension and pH on the activities of the cells were studied. It was found that decreasing the proportion of oxygen in the atmosphere from that of air to 1 per cent reduced oxygen consumption by about 80 per cent, whereas lactic acid production was increased by about 45 per cent. It was also found that decreasing the pH of the medium below pH 7.5 caused a considerable reduction in the respiration, lactate production, and viability of polymorphonuclear leucocytes. The monocytes proved less sensitive to similar changes in pH, especially with regard to lactic acid production and viability.

Observations were made of oxygen consumption and lactate production during phagocytosis. During the hour following the addition of heat-killed tubercle bacilli to the phagocytes, the oxygen consumption of suspensions rich in polymorphonuclear leucocytes rose by 60 per cent, and that of suspensions rich in monocytes rose by nearly 100 per cent. Lactic acid production was unchanged during phagocytosis.
DISTRIBUTION OF BLOOD IN THE FUNCTIONAL KIDNEY
Authors: Weaver A. N. , McCarver C. T. , Swann H. G.
Published: June 2004

An attempt to measure the distribution of blood in the functional kidney of dogs was made. The method involved the injection of liquid latex rubber into the vascular system at physiologic pressures, fixation of the rubber in situ, and then, after corroding away all tissue, measurement of the volume of the rubber casts. The kidney contains, in its functionally distended state, 14 per cent blood. Of this, 4.5 per cent is apparently in the arteries and some 7 per cent in the veins. The functional engorgement of the cortical interlobular veins (about 4 per cent) is particularly striking, for they form a dense palisade of 40 to 300 µ vessels. These are not seen at the usual autopsy since they have drained out and collapsed.

It is pointed out that attempts to describe the blood distribution in the kidney after it has been drained of blood are of dubious value. In the light of these data, also, the nature of the measurement of "intrarenal pressure," accomplished by inserting a needle into the renal parenchyma, may be better understood: it is suggested to be primarily a measure of interlobular venous pressure.
A SEROLOGIC RECAPITULATION OF PAST EXPERIENCES WITH INFLUENZA A; ANTIBODY RESPONSE TO MONOVALENT VACCINE
Authors: Davenport Fred M. , Hennessy Albert V.
Published: June 2004

The results of the present study provide a striking demonstration of antibody orientation produced by the dominant antigens of the strains of influenza virus encountered at childhood. The homologous and heterologous antibody response to monovalent vaccines containing swine, PR8, FM1, or Cuppett viruses show that the antibody-forming mechanisms of children born after 1943 are oriented to strains of influenza A-prime; of recruits to strains of influenza A; and of persons over 30 years of age to a strain of swine influenza. It was shown that antibody response to heterotypic viruses appears to provide a serologic index of the amount of experience each of the segments of the general population studied have had with antigenic variants of influenza virus. Finally it was demonstrated that the antibody response of humans to strains of influenza A or influenza A-prime is remarkably uniform for isolates of each antigenic type.
THE NUTRITIONAL REQUIREMENTS FOR THE PROPAGATION OF POLIOMYELITIS VIRUS BY THE HELA CELL
Authors: Eagle Harry , Habel Karl
Published: June 2004

Only minimal amounts of poliomyelitis virus were formed by HeLa cells placed in a medium free from glucose and glutamine, even if the medium contained an otherwise full complement of essential and non-essential amino acids, purines, pyrimidines, NB4+, and serum protein. Conversely, within one log of the optimal yield of virus was formed by HeLa cells in a medium containing only glucose, glutamine, and salts, even if the cells had been starved in this medium for 12 hours prior to their inoculation.

The presence of glucose alone caused an average 170-fold increase in viral output beyond the amounts formed by the glucose- and glutamine-depleted cells. The addition of glutamine alone caused an average 2000-fold increase; and the addition of both increased the viral formation 40,000-fold. Qualitatively similar results were obtained with unstarved cells, not previously depleted of glucose and glutamine. It follows that only a small proportion of HeLa cells are capable of forming virus unless either glucose or glutamine, or both, are present in the medium.

The elaboration of virus was significantly delayed in media containing glucose but no glutamine.

The absence of glucose and glutamine did not prevent the fixation of poliomyelitis virus by the cell. When these compounds were added to previously depleted cells even 6 hours after inoculation, and after the excess free virus had been removed by washing and by the addition of specific antiserum, normal amounts of virus were formed despite the degenerative changes caused by the previous glucose and glutamine deprivation. Possible functions of glucose and glutamine in the elaboration of virus are discussed in the text.

Such factors other than glucose, glutamine, or salts (e.g. amino acids, purines, pyrimidines, vitamins, protein, or NH4+) as may be needed by HeLa cells for the propagation of poliomyelitis virus, need not be present in the medium and cannot be easily washed out of the cell. Even 12 hours' total deprivation of the cells in salt solution prior to inoculation only slightly decreased their virus-synthesizing capacity in a similarly deficient medium, provided only that adequate amounts of glucose and glutamine were retained.
CROSS-REACTIONS OF ANTITYPHOID AND ANTIPARATYPHOID B HORSE SERA WITH VARIOUS POLYSACCHARIDES
Authors: Heidelberger Michael , Cordoba Felix
Published: June 2004

A study was made of cross-reactions of synthetic polyglucose and of numerous plant and bacterial gums in an antityphoid and an antiparatyphoid B horse serum. The observed differences permit conclusions to be drawn regarding certain of the linkages likely to be found in the fine structures of each of the corresponding Salmonella polysaccharides:—

1. Cross-reactions of the antityphoid serum with the specific polysaccharide of Type II pneumococcus and with tamarind seed polysaccharide, glycogen and synthetic polyglucose indicate that the acetic acid-degraded O-polysaccharide of S. typhi, strain O 901, may contain part, at least, of its glucose as 1,4,6-branch points or in 1,6-linkage, perhaps adjacent to a terminal, non-reducing, galactopyranose unit.

2. Cross-reactions of both antisera with arabogalactans point to the existence of (probably ß-) 1,3-, 1,6-, and/or 1,3,6-linkages of galactose in both the typhoid and paratyphoid B polysaccharides.

3. The differential reactivities of the galactomannans and yeast mannan suggest that the mannose in the typhoid polysaccharide is linked 1,2- or 1,3- with possible non-reducing mannopyranose end groups attached 1,6-. In the paratyphoid B polysaccharide the linkages are probably galacto-oligomannose 1,4-, or 1,4,6-, or the corresponding linkages of mannose alone.
EXPERIMENTAL ENTERIC SHIGELLA AND VIBRIO INFECTIONS IN MICE AND GUINEA PIGS
Authors: Freter Rolf ,   With the Technical Assistance of David Hentges
Published: June 2004

A method has been devised for inhibiting the normal enteric flora, permitting long term asymptomatic enteric infections of mice and guinea pigs with streptomycin-resistant strains of Shigella flexneri or Vibrio cholerae.

Introduction of a streptomycin-resistant strain of E. coli into the intestinal tract of experimental animals resulted in a rapid elimination of the enteric pathogens studied. No in vitro production of antibiotic substances by this coli strain could be demonstrated.

Active and oral passive immunization did not noticeably influence the number of Shigella or Vibrio organisms recoverable from the feces of infected animals.
COPROANTIBODY AND BACTERIAL ANTAGONISM AS PROTECTIVE FACTORS IN EXPERIMENTAL ENTERIC CHOLERA
Authors: Freter Rolf
Published: June 2004

Passive oral immunization with O-antiserum was found to protect guinea pigs against fatal enteric cholera. The number of vibrios recoverable from the intestines of infected animals was not noticeably reduced by active and oral passive immunization.

Passive immunization by the intraperitoneal route was not protective even though high titers of circulating antibody were obtained shortly after injection. Oral administration of H-antiserum also had no protective effect.

Introduction of E. coli into the intestinal tract increased the resistance of guinea pigs to fatal enteric cholera.
DEMYELINIZATION INDUCED IN THE BRAINS OF MONKEYS BY MEANS OF FAST NEUTRONS
Authors: Vogel F. Stephen , Pickering John E.
Published: June 2004

Demyelinization was regularly conspicuous in the white matter of the rostral portions of the brains of 6 monkeys sacrificed 14 to 22 months after exposure of the ocular regions to 850 r.e.p. of 14 mev. neutron radiation and it was not present in the brain of a monkey 2 months after radiation under identical conditions; or in those of 5 non-radiated animals serving as controls. In early lesions, the individual myelin sheaths were varicose and fragmented, while the neurons, axons, and glial cells remained normal in appearance. With the passage of time, the degeneration of myelin became more marked and in later stages was accompanied by a degeneration of the axis cylinders, a proliferation of astrocytes and microglia, and minor cytological changes in the oligodendroglia, the whole process occurring essentially without inflammation or notable changes in the cerebral or meningeal blood vessels. The findings show that neutron radiation has the property of destroying myelin in the living animal and inducing changes that are notably similar in their pathogenesis to those that characterize disseminated encephalomyelitis in human beings.
NEPHROTOXIC SERUM NEPHRITIS IN RATS
Authors: Goodman Howard C. , Baxter James H.
Published: June 2004

A soluble protective factor, capable of absorbing nephrotoxic antibodies from anti-rat kidney serum, can be obtained in high concentration by tryptic digestion of rat kidney homogenate. The factor is no longer antigenic or at most only slightly so. It is stable at 60°, destroyed by boiling, is non-dialyzable, can be precipitated by ammonium sulfate, but resists destruction by proteolytic and other enzymes. In accord with previous studies on the organ localization of the rat tissue antigen responsible for the production of nephrotoxic antibodies, the soluble protective factor, or antigen derivative, can be obtained by tryptic digestion of rat lung, skeletal muscle, heart, and liver.
EXPERIMENTAL PRODUCTION OF GROSS ATHEROSCLEROSIS IN THE RAT
Authors: Fillios Louis C. , Andrus Stephen B. , Mann George V. , Stare Frederick J.
Published: June 2004

Gross atherosclerosis was produced in the rat by feeding purified diets containing cholesterol, sodium cholate, and thiouracil for periods up to 363 days. In a few weeks a marked increase of the serum cholesterol and beta lipoproteins as well as of the liver lipides was observed. Lesions visible in the gross were found on the intimal surfaces of the vessels of all 46 animals examined. These were most prominent in the heart valves and aortic arch. The earliest lesions, which were seen at 31 days, required Sudan staining for gross demonstration. Older lesions were visible without staining. Microscopic coronary artery lesions were present and in one instance were accompanied by massive myocardial infarction. Vascular lesions were characterized by medial and intimal lipide infiltration and cellular intimal plaque formation.

In a part of this study the protein level of the diet was altered at the expense of sucrose. The hypercholesteremic response among the rats varied according to the dietary protein level. The lowest response was observed among those animals receiving the highest level of dietary protein. A difference, however, in the severity and extent of the arterial lesions among these relatively small groups of rats could not be established under these experimental conditions.

In all these experiments a close correlation existed between the serum cholesterol levels and beta lipoproteins of the Sf20–100 range.
ASSOCIATION OF A NEW TYPE OF CYTOPATHOGENIC MYXOVIRUS WITH INFANTILE CROUP
Authors: Chanock Robert M.
Published: June 2004

Viruses producing an unusual "sponge-like" cytopathogenic change in monkey kidney tissue culture were isolated from the pharyngeal swabs of 2 of 12 infants with croup. The infants from whom the viruses were isolated and 3 additional patients developed significant increases in neutralizing or hemagglutination-inhibition and complement-fixing or all 3 varieties of antibody during convalescence. The isolated agents appeared to be similar antigenically.

Fluid from infected monkey kidney tissue culture agglutinated chick erythrocytes and in lower titer human "O" red cells. Hemagglutination occurred best at 4°C. and pH 8.0. Agglutination was reversed at 37°C. but resuspension and sedimentation of red cells at 4°C. resulted in a restitution of positive patterns. In addition, the virus was capable of partially removing receptors from the erythrocyte surface, but only when large quantities of virus were incubated with red cells for 24 hours at 37°C. and small doses of hemagglutinin used to test the treated cells. RDE removed both the erythrocyte receptors and the inhibitor for hemagglutinin present in certain normal sera. Low level multiplication occurred at a slow rate in the amniotic cavity of the fertile hen' egg. Gradocol membrane filtration yielded a size of 90 to 135 mµ. The virus was stable at –70°C. but infectivity was lost after treatment with 20 per cent ether for 15 hours.

The properties of the isolated viruses were consistent with those required for classification in the myxovirus group. No antigenic relationship with influenza A, A', B, and C, Newcastle or Sendai viruses was found. The viruses were distinct from mumps virus but the existence of a common antigen was suggested.

The high incidence of infection with this new virus in one group of croup patients suggests that it may be at least one of the etiologic agents of this clinical syndrome, but more extensive control studies will be necessary to establish a specific etiologic association. For the present the group will be referred to as CA viruses; i.e., croup-associated viruses.
CLONAL GROWTH IN VITRO OF EPITHELIAL CELLS FROM NORMAL HUMAN TISSUES
Authors: Marcus Philip I. , Cieciura Steven J. , Puck Theodore T.
Published: June 2004

Tissue culture strains of cells from four different normal human tissues—liver, conjunctiva, kidney, and appendix—have been grown by the plating procedure previously developed for the HeLa strain of cervical carcinoma cells. This technique results in colony formation from isolated single cells, in a manner completely analogous to the plating of bacteria in semisolid nutrient media.

Clonal cell strains have been isolated from each cell type. All behaved exactly alike in all properties studied except that some differences in plating efficiency were displayed in some of the growth media employed.

The cells from normal human tissues resembled the HeLa S3 carcinomatous cell in the following properties:— (a) Single cells displayed a plating efficiency close to 100 per cent in an appropriate medium. (b) They all grew as an epithelial sheet on glass, the cells being closely packed and polygonal in shape. (c) They had mean generation times of 20 to 23 hours in the nutrient media employed, (d) The mitotic frequency was constant, and therefore the duration of mitosis was the same for all the strains studied, (e) The incidence of multinuclearity and giant formation was very low and similar in both types of cells. (f) Both classes of cells had the same total volume, and the same nuclear cross-sectional area. (g) Both also showed a tendency to spread more in the presence of human serum (concentration of 20 per cent or more) than in porcine serum. However, this differential morphological response was much more marked in the HeLa cell than in those from normal tissues.

The only difference noted in the behavior of these two groups of cells lay in the tendency of the cells from normal tissues always to exhibit a greater cross-sectional area when spread on glass than the HeLa cell in the same medium.

The frequency of occurrence of different types of multinuclearity in the HeLa cell and cells from normal tissues has been measured. The data suggest that multinuclearity depends on two factors: a necessary, predisposing state in the cell, and a random, independent event causing the appearance of an additional nucleus in such a prepared cell.
STUDIES ON THE NATURE AND THE PURIFICATION OF THE COAGULASE-REACTING FACTOR AND ITS RELATION TO PROTHROMBIN
Authors: Tager Morris
Published: June 2004

The coagulase-reacting factor (CRF) of human plasma has been purified, concentrated, and largely freed of prothrombin activity by Seitz filtration, absorbtion on hyflo-amphogel columns, controlled phosphate buffer elution, and fractional ammonium sulfate precipitation.

The purified CRF preparations localized between the beta and the gamma globulin position on paper electrophoresis, and the principal of two components observed on analytical ultracentrifugation gave sedimentation rates between 2.75 and 3.07.

Highly purified prothrombin preparations of Seegers effectively react with staphylocoagulase to lead to the coagulation of plasma.

The electrophoretic and ultracentrifugal properties of the human prothrombin preparations examined differ significantly from those of the purified CRF.

Derivatives of prothrombin, involving a loss of prothrombin activity, such as thrombin and "autoprothrombin," do not correspondingly lose in CRF function.

The hypothesis is proposed that CRF activity is resident in some component or components of the prothrombin molecule not involved in prothrombin function per se, and that therefore prothrombin and CRF activity may either parallel each other when the molecule is intact or diverge when the smaller units only are involved.
FATE OF MYCOBACTERIUM TUBERCULOSIS IN MOUSE TISSUES AS DETERMINED BY THE MICROBIAL ENUMERATION TECHNIQUE
Authors: McCune Robert M. , Tompsett Ralph
Published: June 2004

Observations are presented on the behavior of populations of tubercle bacilli in the tissues of mice during the administration of antimicrobial drugs. The behavior of the populations during therapy with any particular drug was different depending upon whether the tubercle bacilli were subsisting in the lung or in the spleen. Moreover, the pattern of microbial behavior was distinctive and predictable for each drug studied. Changes in the size of the populations of tubercle bacilli in the tissues appeared to be a more sensitive reflection of drug influence than microscopic study of the number and character of the tuberculous lesions. Nevertheless, in untreated animals, pulmonary lesions evolved and progressed steadily to a fatal outcome despite the fact that the populations of tubercle bacilli had stabilized at a relatively high census early in the course of therapy.

The uniform persistence of tubercle bacilli in the spleen throughout prolonged drug administration was demonstrated with every drug or multiple drug regimens except for pyrazinamide when accompanied by isoniazid. Cultures of the bacilli which survived in the tissues despite antimicrobial therapy were highly susceptible to the drugs employed when tested in vitro. Thus the survival of the tubercle bacilli in the tissues represented microbial persistence rather than drug resistance.

When pyrazinamide and isoniazid were administered together, it was not possible to detect the microorganisms in the spleen or lungs of treated animals. A detailed investigation of this apparent abolition of microbial persistence forms the subject of an accompanying report.
CHARACTERIZATION OF LEUKIN: AN ANTIBACTERIAL FACTOR FROM LEUCOCYTES ACTIVE AGAINST GRAM-POSITIVE PATHOGENS
Authors: Skarnes Robert C. , Watson Dennis W.
Published: June 2004

A method has been described for the preparation of a potent antibacterial factor from rabbit polymorphonuclear leucocytes. Upon characterization, the factor was found to possess many properties in common with basic proteins. The amino acid analysis revealed that it contained a relatively large amount of arginine (17 per cent) and small amounts of the other two basic amino acids. It has therefore been identified as a protamine or protamine derivative.

The leucocyte factor was very active against all Gram-positive pathogens tested but exhibited little or no action against Gram-negative species. A possible explanation of this phenomenon has been discussed. The factor was very heat-stable at acid and neutral pH and its staphylococcidal activity was blocked by glutamyl polypeptide, hyaluronic acid, and desoxyribonudeic acid.

Because of the apparent similarity of the product studied here to other poorly defined leucocyte factors which had been termed leukins in the early literature, it is suggested that the name leukin be retained for it. The possible significance of this leukin in natural immunity has been discussed.
CHANGES CAUSED BY INJURIOUS AGENTS IN THE PERMEABILITY OF SURVIVING CELLS OF LIVER AND OF KIDNEY
Authors: Opie Eugene L.
Published: June 2004

Immersion of tissue slices of liver or of kidney in buffered Krebs-Ringer solution at 38°, with oxygenation, gives opportunity for the study of water exchange during 3 hours following removal of the tissue from the body.

Under these conditions a wide variety of physical and chemical agents cause changes in the permeability of the tissue to water, which are referable to the cells of the part; these agents include increased temperature, anoxia, ethyl alcohol, chloroform, bacteria, and bacterial products.

With heating of liver tissue increased permeability reaches a maximum at 50 to 52°C. and is lost at 55° when heat coagulation has occurred.

Permeability of liver cells has increased in the presence of cultures of colon bacilli, of culture filtrate, of killed typhoid bacilli and apparently of diphtheria toxin. Somatic antigen from paradysentery bacilli has caused increased permeability of liver cells.

The experiments indicate that a substance formed by normal metabolism, namely urea, may, under some conditions, increase the permeability of liver cells.
GROWTH CHARACTERISTICS OF TUBERCLE BACILLI AND CERTAIN OTHER MYCOBACTERIA IN HELA CELLS
Authors: Shepard Charles C.
Published: June 2004

By making use of the increased phagocytosis which follows the exposure of HeLa cells to tissue culture media containing selected horse sera, it was possible to introduce all of the mycobacterial species studied into the cells, where many of them proceeded to grow.

Fully virulent strains of tubercle bacilli filled much of the cytoplasm in a few days and formed characteristic cords not seen with other strains. The strains said to be less virulent, R1Rv, BCG, H37Ra, and R1Ra, grew less rapidly and in characteristic patterns. Their rates of multiplication in HeLa cells were in the order named and correlated well with their reported pathogenicity for mice and guinea pigs. Six INH-resistant strains grew at rates characteristic of fully virulent strains.

Among the "rapidly growing" species, M. phlei and M. smegmatis did not show evidence of growth in the cells, although M. fortuitum did.

Some strains with optimal temperatures on bacteriological media below 37°C, M. balnei, M. marinum, and M. platypoecilus, grew rapidly in HeLa cells, especially at temperatures of 31 to 35°C.

The growth patterns of the bacilli in HeLa cells appear sufficiently specific to be useful in differentiation among the mycobacteria.
POSTPARABIOTIC TISSUE REACTIONS OF RABBITS TO MUSCULOFASCIAL CROSS-TRANSPLANTS
Authors: Andresen Richard H. , Monroe Clarence W. , Hass George M. , Madden Dorothy A.
Published: June 2004

Twenty-five pairs of male rabbits of the same variety and strain were joined together in aural parabiosis for 13 to 15 days and then separated from one another. Thirteen pairs of the separated parabiotic twins were surgically united for a second period of parabiosis, less successful than the first due to deficient healing and spontaneous separation of tissue in 5 to 15 days at the site of anastomosis. Within 6 to 90 days after spontaneous or surgical separation of all parabionts, the postparabiotic twins which had been united to one another were cross-grafted with musculofascial transplants. 2 weeks later, the animals were sacrificed and microscopic studies made of the organs and sites of transplantation. These studies disclosed that either one or two periods of parabiosis resulted in the same persistent modification of classical host-homograft interactions. This modification was characterized by the replacement of the customary basic or sensitized homologous incompatibility reactions by a reaction more easily interpreted as one of host-graft tolerance or indifference. The intense inflammatory aspects of the usual host-homograft interactions were absent. Penetration of the musculofascial graft by vascularized mesenchyme derived from the host was retarded. When it occurred, the vascularizing reaction was abnormal and unaccompanied by the customary proliferative, resorptive, and repairative activities of admixed cells of the host and the graft.

These observations provide another means which may be useful in seeking conditions for increasing the probability of successful homografting between members of a genetically impure species.
CYTOLOGICAL AND CYTOCHEMICAL STUDIES OF HELA CELLS INFECTED WITH ADENOVIRUSES
Authors: Boyer Georgiana S. , Leuchtenberger Cecilie , Ginsberg Harold S.
Published: June 2004

The sequential morphological and cytochemical alterations in HeLa cells infected with adenovirus types 1 to 4 are described. Each of the four viruses studied led to consistent and reproducible cytological changes not observed in uninfected control cultures. All four agents produced striking and characteristic changes in the nuclei of infected cells. Alterations in the cytoplasm, though present, were less marked, particularly in the early stages of infection. In cells infected with type 1 or 2 adenovirus, rounded intranuclear inclusions which progressed from eosinophilic and Feulgen-negative to basophilic and Feulgen-positive, together with a homogeneous glassy, Feulgen-positive nuclear background, were prominent features. Cells infected with type 3 or 4 adenovirus exhibited marked rearrangement of basophilic nuclear material and sharply defined crystal-like inclusions, predominantly intranuclear in location, which also varied from Feulgen-negative to positive. In terms of detailed cytological effects, therefore, the four agents could be divided into two subgroups, viz., types 1 and 2 on the one hand and types 3 and 4 on the other. Measurement of DNA in individual nuclei by means of Feulgen microspectrophotometry revealed the values in infected cells to be increased above the levels of the uninfected controls.
FURTHER STUDIES ON THE EFFECTS OF X-RADIATION ON THE MULTIPLICATION OF RICKETTSIA MOOSERI IN EMBRYONATE EGGS
Authors: Greiff Donald , Powers E. L. , Pinkerton Henry
Published: June 2004

The effect of x-rays on the growth of rickettsiae in the embryonate egg was investigated.

The intensifying effect of x-radiation of the host on rickettsial growth can be attributed to alterations of the cells of the host that persist at least 7 days.

The greatest enhancement of the growth of rickettsiae occurred when moderately infected cells were irradiated.

These experiments indicate that x-rays may neutralize or reverse changes in the host that are unfavorable to the growth of rickettsiae.

Explanations of the observed phenomena in terms of biochemical and biological alterations of the cells of the host are discussed.
THE EFFECT OF X-RAYS ON THE RICKETTSIOSTATIC ACTIVITY OF STREPTOMYCIN, AUREOMYCIN, AND PENICILLIN
Authors: Greiff Donald , Powers E. L. , Pinkerton Henry
Published: June 2004

The effect of x-rays on the rickettsiostatic activity of streptomycin, penicillin and aureomycin in the embryonate egg was investigated.

Only a slight reversal of the rickettsiostatic action of 5 mg. of streptomycin occurred in embryonate eggs given 100 r of x-rays at 4 days of incubation, whereas complete reversal occurred in those given 1000 r. Groups of eggs irradiated with intermediate doses of x-rays showed a graded response.

The rickettsiostatic activity of 5 mg. (1660 Oxford units/mg.) of penicillin or of 5 mg. of aureomycin was not reversed by doses of x-rays ranging from 100 to 1000 r.

500 r of x-rays reversed the rickettsiostatic activity of 2 mg., 4 mg., 8 mg., or 16 mg. of streptomycin per egg in proportion to the amount of streptomycin injected. The rickettsiostatic activity of 2 mg. of streptomycin was completely reversed and the activity of 16 mg. only partially reversed.

Reversal of the rickettsiostatic activity of streptomycin by x-rays was observed when radiation was given up to 6 days after the injection of the antibiotic into 7-day-old embryos.

Reversal of the rickettsiostatic activity of 4 mg. of streptomycin could be detected when the antibiotic was injected 3 days after 500 r of x-radiation.

Explanations of the observed phenomena are discussed in terms of biochemical and biophysical alterations of the cells of the host.
STUDIES OF THE MECHANISM OF ACTION OF URETHANE IN INITIATING PULMONARY ADENOMAS IN MICE
Authors: Rogers Stanfield
Published: June 2004

The process of carcinogenesis following exposure of mice to urethane is demonstrated in the present work to be intimately related to nucleic acid synthesis. Injection of animals with a DNA hydrolysate immediately prior to a single exposure of the animals to urethane markedly reduced the number of pulmonary adenomas initiated. Aminopterin, known to interfere in nucleic acid synthesis (46), potentiated the carcinogenic action of urethane and this potentiation was blocked by injection of a DNA hydrolysate.

Of the components and precursors of nucleic acids the pyrimidine series seemed especially concerned. Alterations in the utilization of oxaloacetate, ureidosuccinic acid, dihydro-orotic acid, orotic acid, cytidylic acid, and thymine appeared to be critical steps in the oncogenic process, following upon the primary disorder of cellular metabolism initiated by the carcinogen. All these substances except oxaloacetate profoundly reduced the number of tumors initiated by urethane. Oxaloacetate potentiated the carcinogenic effect.

When these results are viewed together and in relation to known facts concerning nucleic acid synthesis they provide evidence suggesting that the point of action of the carcinogen is in the pathway of nucleic acid synthesis below orotic acid and perhaps at the level of ureidosuccinic acid.

The potentiating influence of adenine, 4-amino-5-imidazole carboxamide, and aminopterin, the lack of effect of uracil, and the inhibitory influence of thymine together suggest that DNA rather than RNA is the nucleic acid critical to the oncogenic response of mice to urethane.
CELL-FREE TRANSMISSION IN ADULT SWISS MICE OF A DISEASE HAVING THE CHARACTER OF A LEUKEMIA
Authors: Friend Charlotte
Published: June 2004

A disease with the characteristics of a leukemia has been found to be serially transmissible in adult Swiss mice by means of cell-free filtrates. Thus far, the disease has been transmitted through twenty-six serial passages with filtrates as well as cell suspensions. The agent readily passes through Selas 03, Berkefeld N, and gradocol membrane filters—these last having an average pore size of 220 mµ. Filtrates remain stable when stored for long periods at –70°C. or when lyophilized. Splenic tissue containing the agent, which was subjected to massive doses of x-ray (50,000 r),—far more than sufficient to kill the cells,—show undiminished infectivity. The agent is inactivated by heating to 56°C. for 30 minutes and by exposure to ether or formalin.

The disease can be transmitted to adult Swiss mice or DBA/2 mice, but not to adult PRI, C3H, A, C57B1/6, or F1(C58 x BALB) mice. Intraperitoneal, subcutaneous, intracerebral, and intramuscular injections are all effective.