bluuebunny/crossref_metadata_2025 huggingface dataset:
THE EFFECT OF EGG YOLK IN DIETS ON ANAPHYLACTIC ARTHRITIS (PASSIVE ARTHUS PHENOMENON) IN THE GUINEA PIG
Authors: Coburn Alvin F. , Graham Claire E. , Haninger Joan
Published: June 2004

Whole egg yolk incorporated as a supplement in the diet of baby guinea pigs afforded protection against anaphylactic arthritis as determined: (a) by measurement of joint swelling; (b) by the rise in serum level of some substance which reacts with diphenylamine; (c) by histologic examination.

The active material in egg yolk was shown to be in the alcohol-soluble fraction. Attempts to identify the active material with any known lipid have to date been unsuccessful.

In the screening of lipid substances for protection against anaphylactic arthritis, it is shown that the weanling guinea pig is suitable, that a 3 week period is adequate, and that the test substance can be administered satisfactorily in the diet.
SOME OBSERVATIONS ON THE INTRACELLULAR LOCALIZATION OF THE VIRUS OF HERPES SIMPLEX IN THE CHICK EMBRYO LIVER
Authors: Gray Alan , Scott T. F. McNair
Published: June 2004

The growth cycle of the virus of herpes simplex in chick embryo liver has been shown to follow the same pattern as in the chorioallantoic membrane and the rabbit's corneal cells. However, there is considerable variability in the time taken for the yolk sac-inoculated virus to get from the yolk sac into the liver.

A brief description has been given of various fractionation procedures employed for obtaining isolated nuclei. It has been shown that free virus is not selectively adsorbed to isolated nuclei. Evidence has been presented to show that in the herpes-infected chick embryo liver, large proportions of the total virus can at times be found associated with the nuclear fraction. The percentage of the total virus in the nuclear fraction varies inversely with the titer of virus in the whole liver, and the number of hours after inoculation of the virus; only a negligible amount (as compared with that in the total) being associated with the nuclear fraction when a period of over 12 hours has elapsed after reappearance of virus. Furthermore, demonstration of virus in the isolated nuclei following extraction with hypertonic NaCl provides additional evidence that this virus is intimately associated with the nuclei.
II. ANTIGENICITY OF GELATIN IN RABBITS AND OTHER SPECIES
Authors: Maurer Paul H.
Published: June 2004

Normally occurring antibodies to gelatin have been demonstrated in sera from many species.

Immunization of rabbits with gelatin has been successful when adjuvant techniques were employed.
THE NATURE OF PROPHAGE IN LYSOGENIC BACILLUS MEGATHERIUM
Authors: Miller Elizabeth M. , Goebel Walther F.
Published: June 2004

1. By complement-fixation tests it has been shown that the lysogenic and sensitive strains of B. megatherium share one or more antigenic components which are serologically related but not identical.

2. Bacilli of the lysogenic strain of B. megatherium, when grown under conditions such that little extracellular phage is produced, fail to evoke antibodies in rabbits which react either in complement-fixation or neutralization tests with purified megatherium T phage. From this it must be concluded either that prophage is not antigenic or that any antibody which it might elicit does not react with the antigens of the mature virus.

The observations reported in this communication accord with the hypothesis that prophage is a genetic structure.
INFLUENZA VIRUS MULTIPLICATION IN THE CHORIOALLANTOIC MEMBRANE IN VITRO: KINETIC ASPECTS OF INHIBITION BY 5, 6-DICHLORO-1-ß-D-RIBOFURANOSYLBENZIMIDAZOLE
Authors: Tamm Igor , Tyrrell David A. J.
Published: June 2004

A procedure is described for kinetic studies on the multiplication of Lee virus in the chorioallantoic membrane in vitro employing the hemagglutination technique for measurement of virus concentration. A linear relationship was found between the logarithm of virus adsorbed and the amount of membrane used. Of the virus adsorbed less than 10 per cent could be recovered from the membrane. Of the recoverable virus 90 per cent was eliminated by specific immune serum. Lee virus was adsorbed by the allantoic and chorionic layers of the membrane to a similar degree. Multiplication occurred in both layers and to a similar extent. When 107.66 EID50 of Lee virus was inoculated per 2.9 cm.2 of chorioallantoic membrane, the ratio of infectivity to hemagglutination titer in the yield was low, although the rate of appearance of virus particles was not diminished despite the large inocula.

Virus produced in membranes was liberated rapidly and continually into the medium. 5,6-Dichloro-1-ß-D-ribofuranosylbenzimidazole (DRB), 0.000055 M, prolonged the latent period by more than 100 per cent. The rate of increase during the period of rapid rise was similar in the presence or absence of DRB, but the yield was markedly reduced at the end of this period in the presence of DRB. The amount of the virus in the membranes continued to rise in the presence of DRB and eventually approached the maximal levels reached much earlier in the controls. Measurement of the amount of virus in the media indicated a greater degree of inhibition than did measurement in the membranes. Comparative studies with two benzimidazole derivatives on the dependence of the inhibitory effect on the time of addition of the compound showed that processes which could be inhibited by DRB were of shorter duration than those inhibited by 2,5-dimethylbenzimidazole (MB). With MB the relationship between the time of addition and the inhibitory effect was similar both for virus and for soluble complement-fixing antigen; with DRB the inhibitable processes were of shorter duration for the complement-fixing antigen than for virus particles. DRB was not only 35 times more active on a molar basis but also was more selective in its action than MB. DRB interfered with processes which preceded the emergence of either soluble complement-fixing antigen or virus particles. Some of the implications of these findings are discussed in relation to the mechanism of inhibition of influenza virus multiplication by benzimidazole derivatives.
RELATION OF CERTAIN ENDOCRINE DISTURBANCES TO SUSCEPTIBILITY OF GOLDEN SYRIAN HAMSTER TO EXPERIMENTAL POLIOMYELITIS
Authors: Teodoru Constantin V. , Shwartzman Gregory
Published: June 2004

Alterations in susceptibility of the Syrian hamster to poliomyelitis virus (MEF1) inoculated intracerebrally appeared closely related to seasonal changes and experimental disturbances in the adreno-testes equilibrium. Enhanced susceptibility coincided with seasonal enlargement of adrenals, followed cortisone and DOCA treatment and appeared during the initial postorchiectomy period. Increased resistance occurred incidentally to adrenalectomy, seasonal diminution in adrenal weight, testosterone overdosage, and testicular hypertrophy induced by treatment with GTH or chorionic gonadotrophin.

The effect of certain hormonal interactions, the interference of conditioning factors and the role of compensatory reactions are discussed.
STUDIES ON THE ENDOPLASMIC RETICULUM
Authors: Palade George E. , Porter Keith R.
Published: June 2004

A series of representative cell types including avian fibroblasts, and macrophages; rabbit mesothelia, endothelia, and nephron epithelia; and rat glandular epithelia (parotid) were studied comparatively in vitro and in situ with the electron microscope. Cells in vitro were examined in whole mounts and in sections whereas cells in situ were observed exclusively in sections.

It was found that an endoplasmic reticulum similar to that previously described in cultured material is present in situ in all cell types examined.

Modifications in its appearance introduced by the sectioning technique were discussed and explained. The observations showed in addition that the endoplasmic reticulum is a network of cavities which may enlarge into relatively vast, flattened vesicles here described as cisternae.
IMMUNOCHEMICAL STUDIES OF ANTITOXIN PRODUCED IN NORMAL AND ALLERGIC INDIVIDUALS HYPERIMMUNIZED WITH DIPHTHERIA TOXOID
Authors: Kuhns William J.
Published: June 2004

Studies were carried out on sera from eight subjects hyperimmunized with toxoid who developed marked immediate skin reactivity to toxoid associated with circulating non-precipitating antitoxin. With the use of the rabbit skin test, the agar diffusion technique, and three different methods for passive transfer of skin sensitivity, it was possible to obtain detailed qualitative and quantitative data relating to the antitoxin in these sera. It was found that specimens from six individuals contained only skin-sensitizing antitoxin. Two sera showed a lack of parallelism between antitoxin titers as obtained by rabbit skin test and titers as demonstrated by tests in human skin. It was presumed that these sera contained two different varieties of non-precipitating antitoxins, and that only one of them was skin-sensitizing antitoxin.

A new technique is described for measurement of skin-sensitizing antitoxin. Its specificity is based upon the ability of this antitoxin to remain at skin sites and later neutralize the delayed specific toxic effects of intradermal Schick test reagent.
INTRACELLULAR CHANGES DUE TO NEUTRAL RED AS REVEALED IN THE PANCREAS AND KIDNEY OF THE MOUSE BY THE ELECTRON MICROSCOPE
Authors: Weiss Jules M.
Published: June 2004

The effects of sublethal amounts of the cationic dye, neutral red, upon the structure of pancreatic exocrine cells, and upon the mitochondria of renal distal tubule cells, have been studied with the electron microscope. It was found that neutral red is a cytoplasmic toxin which causes reproducible and characteristic changes in the ergastoplasm, the zymogen granules, the mitochondria, and possibly in the Golgi complex. Ergastoplasmic membranes and granules and zymogen granules lose definition and become continuous with the cytoplasmic matrix. Mitochondria lose their internal folds, develop vacuoles which contain a solution of neutral red in high concentration, and form the nidus for the development of sudanophilic, argyrophilic, osmiophilic inclusions which appear in the cytoplasm after neutral red administration. Golgi granules, one of the three elements of the Golgi complex, appear to increase in number and to be scattered more widely through the cytoplasm than is normal. No consistent changes were found in the cell membrane or nucleus.

The ability of the mitochondria to concentrate the cation, neutral red, taken with its well known ability to concentrate the cationic Janus dyes and methylene blue, and its probable role in concentrating those cationic dyes which have been used to demonstrate the "vacuome," is interpreted to signify that one of the functions of mitochondria may be to concentrate intracellar cations.
EFFECTS OF LARGE INFUSIONS OF HETEROLOGOUS SERUM PROTEINS ON THE SERUM PROTEIN METABOLISM OF RABBITS
Authors: Dixon Frank J. , Maurer Paul H.
Published: June 2004

Infusions of heterologous serum proteins large enough to replace the entire normal catabolic loss of the corresponding autologous proteins in the recipient rabbits caused increased rates of plasma protein catabolism, an increase in the size of the plasma protein pool and normal or even slightly increased rates of plasma protein synthesis. The principal proteins in these infusions were catabolized at rates similar to those for corresponding homologous proteins. The most marked hyperproteinemias which developed were caused principally by increases in the host's own globulin and to a lesser extent by the presence of foreign protein in the circulation.
A FRACTION OF TUBERCLE BACILLI POSSESSING PRIMARY TOXICITY
Authors: Spitznagel John K. , Dubos René J.
Published: June 2004

Tubercle bacilli separated from young cultures were thoroughly extracted with monochlorobenzene at temperatures never exceeding 50°C. From the soluble material, a fraction corresponding to approximately 1 per cent of the total bacillary weight was separated by fractional precipitation with petrolic ether at temperatures of 0° or 4°C.—depending upon the strain of bacilli.

The monochlorobenzene-soluble-ether-insoluble material (fraction 7) prepared from BCG-P was found to contain 0.14 per cent nitrogen and 0.4 per cent phosphorus. Some of its other chemical characteristics are described.

Fraction 7 proved unable to elicit tuberculin allergy in guinea pigs, but injection of 5 µg. of it into the skin produced severe local reactions.

In albino mice, a single intraperitoneal injection of 20 µg. caused loss of muscular tone and of weight followed by death within 9 days. The only tissue reaction observed was a slight degree of peritonitis. In mice of the C57 BL strain, a single injection of 40 µg. also caused death in the same time, but with pulmonary hemorrhages—usually massive.

Material similar to fraction 7 was obtained from one virulent, two attenuated, and one avirulent strain of mammalian tubercle bacilli (bovine and human). The fractions obtained from the various strains differed somewhat in solubility and toxicity. The more virulent the culture, the more toxic was the fraction obtained from it; but it is possible that this relation was the result of differences in the effectiveness of the extraction procedures, rather than of characteristics inherent to the cultures.

Evidence is presented that the toxicity of fraction 7 accounts for much of the primary toxicity of tubercle bacilli.
ANTITUBERCULOUS IMMUNITY INDUCED IN MICE BY VACCINATION WITH KILLED TUBERCLE BACILLI OR WITH A SOLUBLE BACILLARY EXTRACT
Authors: Weiss David W. , Dubos René J.
Published: June 2004

It proved possible to increase the resistance of mice to tuberculous infection by vaccinating them with a suspension of avirulent tubercle bacilli killed by exposure to 2 per cent phenol. This increase in resistance was demonstrated by two different techniques: (a) observation of survival time of vaccinated animals following challenge infection with a large dose of virulent bacilli, and (b) determination of numbers of virulent bacilli in the spleens of animals 2 weeks after injection of a small infective dose.

The minimum protective dose of vaccine corresponded to approximately one-tenth the acutely toxic dose.

Addition of an adjuvant to the bacillary suspension markedly increased both the protective effectiveness of the vaccine and the duration of the immunity. It enhanced also the toxicity of the vaccine in approximately the same proportion. However, other lines of evidence suggested that toxicity and protective activity were independent one from the other and were the manifestations of different bacillary constituents.

Extraction with absolute methanol released from the bacillary bodies a crude soluble fraction possessing low, if any, toxicity, yet capable of eliciting in mice a state of increased resistance to virulent infection. The protective activity of this methanol-soluble fraction was low; it accounted for only a small part of the total protective activity of the original material.
STUDIES ON THE ANTIPYRETIC ACTION OF CORTISONE IN PYROGEN-INDUCED FEVER
Authors: Atkins Elisha , Allison Fred , Smith Mary Ruth , Wood W. Barry
Published: June 2004

The mode of action of cortisone as an antipyretic has been studied in rabbits challenged with intravenous injections of bacterial pyrogens. The fever induced by pyromen or dextran was found to be markedly suppressed when cortisone was administered in liberal amounts (25 mg. twice daily) for 3 days prior to the challenge. Although the cortisone effectively blocked the febrile response to both pyrogens, it failed to influence the transient but marked leucopenia which characteristically precedes the onset of fever.

The antipyretic action of the drug also was shown to bear no relation to the activity of the serum factor recently demonstrated by Farr, Grant, and others to be involved in the production of pyrogen-induced fever. In preliminary experiments with typhoid vaccine as the inciting pyrogen, the presence of serum factor activity in normal blood and its absence in the blood of pyrogen-tolerant rabbits was confirmed. Subsequently the blood of rabbits treated with antipyretically effective doses of cortisone was shown to contain just as much serum factor activity as that of normal rabbits. In addition, previous incubation of the pyrogen with serum factor failed to influence the antipyretic effect of the drug.

It is concluded from these findings that in suppressing pyrogen fever, cortisone acts neither upon the leucopenic reaction nor upon the fever-accelerating factor of the serum. By exclusion it would appear that the drug must influence some later stage of the fever-producing process. The mechanisms involved in the later stages of the response to exogenous pyrogen remain undefined, and the need for determining whether they are related to the prefebrile leucopenia is emphasized.
SPECIFIC AGGLUTINATION OF TREPONEMA PALLIDUM BY SERA FROM RABBITS AND HUMAN BEINGS WITH TREPONEMAL INFECTIONS
Authors: Hardy Paul H. , Nell E. Ellen
Published: June 2004

A method has been described for the preparation of Treponema pallidum suspensions that are suitable for specific agglutination studies and can be stored at 4°C. for months without loss of agglutinability. Such suspensions have been shown to react with two distinct antibodies in the serum of syphilitic animals and man: Wassermann antibody and a specific treponeme agglutinin.

It has been demonstrated that the agglutination of treponemes by specific treponeme agglutinin is enhanced by heat treatment or aging of the suspension, and inhibited by a divalent cation, probably Ca++, normally present in serum. This inhibition has been overcome by the use of a chelating agent, ethylene-diamine tetracetate.

These findings have been utilized to devise a simple agglutination test for the diagnosis of treponeme infections that is very sensitive and highly specific. This test has been carried out with 430 human sera, and a comparison has been made of the results of the agglutination, treponemal immobilization, and standard serological tests on these sera. The agglutination test appears to have a specificity comparable to the treponemal immobilization test and considerably greater than the standard serological tests.
ERYTHROCYTE LIFE SPAN IN GROWING SWINE AS DETERMINED BY GLYCINE-2-C14
Authors: Bush J. A. , Berlin N. I. , Jensen W. N. , Brill A. B. , Cartwright G. E. , Wintrobe M. M.
Published: June 2004

Red blood cell survival studies were performed on five normal growing swine by following the C14-specific activity of hemoglobin and heme after the administration of glycine-2-C14. The erythrocytes of normal growing swine appear to be destroyed both by a random and an age-dependent process. Random destruction accounts for the larger portion of the cells which are destroyed.

The "mean" red cell survival time was 62 days. This represents the interval from the time of incorporation of 50 per cent of the maximal amount of labelling achieved to the time when the level had decreased once more to the 50 per cent amount. The " ‘corrected’ average potential life span" of the red cells was 86 ± 11.5 days. This figure was obtained by subtracting the number of days required to attain 80 per cent of the maximal labelling from the average survival time of red cells destroyed by an age-dependent process as distinguished from random destruction.
STUDIES ON HOST-VIRUS INTERACTIONS IN THE CHICK EMBRYO-INFLUENZA VIRUS SYSTEM
Authors: Finter Norman B. , Liu Oscar C. , Henle Werner
Published: June 2004

An analysis has been made of factors contributing to the von Magnus phenomenon; i.e., the emergence of increasing quantities of non-infectious hemagglutinins (NIHA) in successive passages in the allantois of chick embryos of undiluted allantoic fluids infected with influenza virus.

Using the PR8 strain, the von Magnus phenomenon was pronounced when the serial seeds were obtained under conditions which permitted extensive inactivation of infectious virus during individual passages. Correspondingly, it was reduced but not abolished when precautions were taken to avoid accumulation of inactivated virus in the inocula. Thus, inactivated virus may be taken as a contributing factor.

Preparations of infectious virus obtained under conditions largely excluding the presence of inactivated virus were capable of yielding some NIHA on passage as long as sufficient amounts were injected to permit each host cell to adsorb several infectious virus particles. However, the fact remains that more NIHA was found in the harvests when the inocula contained a large proportion of non-infectious virus material.

Following injection of various types of seeds NIHA appeared in the allantoic fluids as soon as liberation of virus became detectable. This time relationship and the rates of release of non-infectious virus components seemed to exclude that the NIHA obtained consisted entirely of infectious virus which had been inactivated during incubation in ovo. It was apparent rather that NIHA other than that due to heat-inactivated virus was released.

Correlations between the infectivities and hemagglutinating capacities of over 50 standard and undiluted passage seeds and the compositions of the harvests derived therefrom on passage without dilution indicated that the corresponding activities in the yields did not depend entirely upon the relative concentrations of infectious virus and non-infectious hemagglutinins in the inocula but that apparently different forms of NIHA were obtained in successive undiluted passages.
THE USE OF PRECIPITIN ANALYSIS IN AGAR FOR THE STUDY OF HUMAN STREPTOCOCCAL INFECTIONS
Authors: Halbert Seymour P. , Swick Lois , Sonn Constance
Published: June 2004

Using a highly concentrated and partially purified streptolysin O preparation, migrating agar precipitins have been found in 94 of 143 human sera from patients with a variety of diseases. Most of those showing no bands, had very low antistreptolysin titers.

A correlation was found between the migration rates of these bands and the antistreptolysin titer. A strong trend toward a straight line relationship was apparent when the ASO titers were plotted on a logarithmic scale. In addition, a roughly positive correlation was found between the intensity of these bands and the antistreptolysin O titers. The finding of high levels of antistreptolysin O activity and slowly migrating heavy bands in normal pooled human gamma globulin supported the above observations.

Very similar results were obtained with rabbit and guinea pig sera after immunization with the streptolysin O concentrates.

The data strongly indicate that antistreptolysin O activity in human sera is generally due to precipitating antibody, and that non-specific inhibitors are not usually involved, even with low titered sera.

Rabbit and guinea pig antisera to the oxidized inactive and to the reduced active forms of streptolysin O showed no obvious differences. Attempts to demonstrate immunological differences between the two states of streptolysin were apparently complicated by proteolysis, due to contamination of the concentrates with proteinase precursor.
STUDIES ON INFLUENZA INFECTION IN FERRETS BY MEANS OF FLUORESCEIN-LABELLED ANTIBODY
Authors: Liu Ch'ien
Published: June 2004

By means of fluorescein-labelled antibody staining, specific influenza viral antigens were seen in both the cytoplasm and the nucleus of infected ciliated epithelial cells covering the nasal turbinates of infected ferrets. Initially, only a small portion of the nasal epithelium showed fluorescence, and no appreciable abnormality of the cells could be detected by hematoxylin and eosin staining. The fluorescence soon spread to involve the entire epithelium, followed by desquamation coinciding with the onset of manifest illness. Pneumonia was seen in some of the infected ferrets, and in them, viral antigens were found in the bronchial epithelium and in the mediastinal lymph nodes. A rise of viral infectivity titer paralleled the observed spread of viral antigens.

Many desquamated nasal epithelial cells and macrophages containing antigen were present in nasal smears. The finding would seem to offer a method for the rapid specific diagnosis of influenza infection.
EXPERIMENTAL NEEDLE BIOPSY OF THE MYOCARDIUM OF DOGS WITH PARTICULAR REFERENCE TO HISTOLOGIC STUDY BY ELECTRON MICROSCOPY
Authors: Price Kenneth C. , Weiss Jules M. , Hata Daikichi , Smith John R.
Published: June 2004

Our experience with needle biopsy of the heart in dogs indicates that myocardial tissue can be sampled one or more times in each animal with comparative safety. Tamponade, pericarditis, serious arrhythmias, or myocardial infarction due to the interruption of coronary vessels was not observed. Excellent specimens were obtained for critical study by light and electron microscopy. Casten and Marsh (1) have used biochemical techniques to study myocardial tissue obtained in similar fashion. Histochemical methods would also be applicable.

Although limited to animal studies at present, the technique may conceivably be adapted to the study of human disease. Myocardial puncture has been carried out (20–22) in patients for the recording of intracardiac pressures and for other diagnostic purposes without apparent harm.

Our study of the myocardium of dogs by electron microscopy generally confirms the observations of other workers, except that presence of significant numbers of red blood cells in the extravascular spaces of the heart had not been previously described (and is possibly an artifact). Nevertheless, it is notable that the tissue cells, cellular membranes, and intracellular structures appeared to be intact and undistorted in the tissue specimens which were obtained, fixed, and examined by these methods.
STUDIES ON ANTIBODY PRODUCTION
Authors: White Robert G. , Coons Albert H. , Connolly Jeanne M.
Published: June 2004

After injection of ovalbumin as a water-in-oil emulsion a pronounced adjuvant effect is demonstrable following the incorporation of tubercle bacillary wax into the oily phase of the mixture. With single doses of antigen (10 mg. ovalbumin) there is a 4- to 5-fold increase in the amount of antibody at the median of 3 week serum levels in animals receiving a small dose of wax (40 µg.). With a 5 mg. dose of wax there is an 8-fold increase in serum antibody levels at the median.

A striking feature of the action of wax is the stimulation of a macrophage proliferation locally at the site of injection, and the production of morphological abnormalities in these cells. As judged by staining techniques for antibody content, these locally assembled cells are not active in the formation of antibody. Wax injected in mineral oil results in a remarkable systematized stimulation of the reticulo-endothelial system.

The greatly increased serum antibody levels demonstrated after the use of tubercle bacillary wax in antigen mixtures is attributed to a widespread proliferation of plasma cell elements in the lymphatic glands, spleen and liver.
STUDIES ON RENAL JUXTAGLOMERULAR CELLS
Authors: Hartroft Phyllis Merritt , Hartroft W. Stanley
Published: June 2004

Many of the observations made by Deane and associates (8, 13, 14) regarding the effects of salt restriction, excess salt intake, and hypophysectomy on the zonna glomerulosa of the adrenal cortex in the rat have been confirmed.

A positive correlation (r = 0.63) of high statistical significance has been demonstrated between the degree of granulation of JG cells (JGI) and the width of the zona glomerulosa in 159 rats from 5 series of experiments in which low, normal, and high salt regimens were employed. A somewhat higher correlation (r = 0.81) was obtained when only rats were included from the most recent experiment of the series in which JGI counts were more accurate. Under the conditions of these experiments, therefore, increased granulation and degranulation of JG cells were associated with hyperactivity and suppressed activity, respectively, of the zona glomerulosa.

Rats sacrificed 4 to 7 weeks after hypophysectomy were found to have normal JG cells. This finding constitutes another example of the similarity in response of JG cells to that of the zona glomerulosa, which also remained unaltered following hypophysectomy despite atrophy of the rest of the adrenal cortex.
STUDIES ON THE GENERALIZED SHWARTZMAN REACTION
Authors: Thomas Lewis , Smith Richard T. , von Korff Richard
Published: June 2004

An intravenous injection of sodium polyanethol sulfonate, a heparin-like synthetic polymer of large molecular size, into rabbits given endotoxin 2 hours previously, results in the abrupt disappearance from the circulating blood of a large proportion of fibrinogen. The depletion of circulating fibrinogen is prevented by the administration of heparin prior to the synthetic polymer. In animals receiving the polymer alone, or endotoxin alone, no depletion of fibrinogen occurs.

It is suggested that the intravascular deposition of fibrinoid and the subsequent necrotizing lesions of the generalized Shwartzman reaction, which occur after the combined injection of endotoxin and synthetic acid polymer, may be due to the intravascular precipitation of fibrinogen by polymer.

A qualitative change in fibrinogen, characterized by its precipitability by heparin at low temperature, is regularly demonstrable in plasma between 1 and 4 hours after an intravenous injection of endotoxin. The appearance of this heparin-precipitable fraction is prevented by treatment with heparin before endotoxin. It is not influenced by nitrogen mustard or cortisone.

During the period when depletion of circulating fibrinogen is produced by polyanethol, in endotoxin-treated animals, the heparin-precipitable fraction also disappears from the blood.

It is suggested that the change in fibrinogen may represent partial polymertization, and the cold precipitability of this material by heparin may be related to its enhanced precipitability, in vivo, by polyanethol.

An hypothesis which accounts for certain events in the generalized Shwartzman reaction, based on observations reported in this study, is presented.
MAST CELLS AS SOURCES OF TISSUE HISTAMINE
Authors: Graham Helen Tredway , Lowry Oliver H. , Wahl Nancy , Priebat Martha K.
Published: June 2004

Enumeration of mast cells and determination of histamine in sections of dog skin and dog lung have shown that the regions of the tissue rich in mast cells are also rich in histamine. In the skin, the outer layers of the dermis contain higher concentrations of histamine and mast cells than any other region.

Average values of the histamine content and mast cell count for dog liver, heart, muscle, and kidney, and for beef liver parenchyma and capsule, also exhibit a positive relationship between these two parameters, although the amount of histamine found per mast cell varied from 7 µµg. in dog skin to 32 µµg. in beef liver capsule.

When the size of the mast cells was taken into account, the intracellular concentration of histamine was found to be of the same order (about 0.4 molar) for all the tissues examined except skin and kidney. In both dog skins analyzed, the intracellular concentration was about 0.1 molar. In kidney both mast cell and histamine values were too low for accurate estimation.

The concentration of histamine in the mast cells investigated was much greater than the concentration in human basophils, the blood elements richest in histamine.

The mechanism of the localization of histamine in mast cells is briefly considered.
THE DEPRESSION OF ESTRONE-INDUCED UTERINE GROWTH BY PHENOLIC ESTROGENS WITH OXYGENATED FUNCTIONS AT POSITIONS 6 OR 16: THE IMPEDED ESTROGENS
Authors: Huggins Charles , Jensen Elwood V.
Published: June 2004

Two small groups of steroids in the estrane series—here designated as impeded estrogens,—represent a class of compounds which differ from the majority of estrogenic substances in exerting certain unusual influences on growth of the uterus. The induction of these effects previously was considered to be peculiar to estriol. The unusual growth properties common to impeded estrogens are twofold: (a) after the threshold dosage required to initiate growth has been reached, the slope of the curve of increment of uterine weight in response to increased steroid dosage is very gradual rather than steep; (b) these compounds possess the ability to inhibit to a limited extent the uterine growth induced by estrone administered concurrently.

The partial inhibition of estrone-induced growth of the uterus is confined to a critical dosage of the impeded estrogen and is overcome by increased dosage of the inhibitor. Estrone-induced growth of the vagina is not inhibited by impeded estrogens. Furthermore the simultaneous administration of impeded estrogens and testosterone does not lessen the amount of uterine growth evoked by the latter.

The impeded estrogens so far encountered are 3-hydroxyestratriene derivatives possessing either a ketone group at position 6 or a hydroxyl group at position 16. Oxygenated functions at these positions in phenolic estrogens have special significance in the excitation and restraint of uterine growth unshared by similar groups at certain other sites of the estrane molecule.
THE DEPRESSION OF GROWTH OF THE UTERUS, ADRENALS, AND OVARIES BY FLUORINATED STEROIDS IN THE PREGNANE SERIES
Authors: Huggins Charles , Jensen Elwood V.
Published: June 2004

Progesterone, 5-pregnene-3,20-dione, and desoxycorticosterone were found to be partial but significant inhibitors of estrone-induced growth of the uterus of hypophysectomized rats but they did not depress the amount of growth elicited by testosterone.

The presence of both the 2-carbon side chain at position 17 and an oxygenated function at position 3 is necessary for the inhibitory activity of progesterone. The introduction of a hydroxyl group in the progesterone molecule at positions 6 (ß), 11 (α), 16 (α) or 17 (α) destroyed its growth-inhibitory activity.

11ß-Hydroxyprogesterone is weaker than progesterone in the inhibition of estrone-induced uterine growth; unlike progesterone it has the capacity to depress growth elicited by testosterone.

The introduction of a flourine atom in the 9 (α) position resulted in a striking increase of the growth-inhibitory activity of 11ß-hydroxyprogesterone and hydrocortisone.

9α-Flouro-11ß-hydroxyprogesterone is a partial but significant inhibitor of growth of the uterus in hypophysectomized rats injected simultaneously with large doses of estrone or testosterone. It is more powerful than progesterone in transforming the vaginal epithelium to mucus cells in the presence of estrone. Administered alone, the only detectable growth was a slight increase in size of the preputial glands.

9α-Flouro-11ß-hydroxyprogesterone suppresses in part the growth of the adrenals, ovaries, and uterus in intact rats at a dose level which does not cause loss of body weight or inhibit body growth. Many rats treated with this compound in small amount had extensive mucification of the vagina resembling that of late pregnancy.
STUDIES ON SUSCEPTIBILITY TO INFECTION FOLLOWING IONIZING RADIATION
Authors: Hammond Carolyn W. , Ruml David , Cooper Dorothy B. , Miller C. Phillip
Published: June 2004

Pseudomonas aeruginosa introduced directly into the stomach established itself more regularly in the intestinal tract of irradiated mice than of unirradiated mice. The irradiated mice had been exposed to 550 r total body x-irradiation 5 days before inoculation.

This difference between irradiated and unirradiated mice could not be explained by differences in pH of gastric or duodenal contents, propulsive motility of the intestinal tract, or the ability of the intestinal contents to support growth of Pseudomonas in vitro.
AMINO ACID COMPOSITION AND ELECTROPHORETIC PROPERTIES OF HYPERTENSIN I
Authors: Skeggs Leonard T. , Marsh Walton H. , Kahn Joseph R. , Shumway Norman P.
Published: June 2004

A preparation of hypertensin I was purified by countercurrent distribution and was shown to migrate as a single component in starch blocks at pH 9.3 and 4.2. It had an isoelectric point of 7.7. Quantitative analysis by ion exchange column chromatography showed eight amino acids in approximately unimolar proportion: aspartic, proline, valine, isoleucine, leucine, tyrosine, phenylalanine, and arginine. There were in addition two moles of histidine.
TENDOVAGINITIS WITH ARTHRITIS, A NEW SYNDROME OF CHICKENS: ISOLATION AND CHARACTERIZATION OF AN INFECTIOUS AGENT
Authors: Lecce J. G. , Sperling F. G. , Hayflick L. , Stinebring W.
Published: June 2004

The findings with an infectious agent isolated from cases of tendovaginitis or arthritis of chickens were as follows:—

Cultures, stains, and darkfield studies of material containing this agent for spirochetes, bacteria, and pleuropneumonia-like organisms were negative.

The yolk sac was the preferred route of inoculation, all of the embryos dying in 4 to 12 days.

The agent passed through a bacteria-retaining filter, but with a drop in titer.

Antibiotic sensitivity tests revealed that the agent was most sensitive to the tetracycline antibiotics, less sensitive to chloromycetin, dihydrostreptomycin, and resistant to penicillin.

From electron micrographs it was concluded that the agent is a rigid, dense, coccobacillus from 0.2 µ to 0.5 µ, in size.

The agent produced a cytopathogenic effect in tissue cultures of chick heart fibroblasts.

The agent had no gross effect on suckling or newly weaned mice, pigs, or guinea pigs.

Reasons for suggesting that the agent is most similar to a rickettsia or possibly a large virus are discussed.
STUDIES ON THE PATHOGENESIS OF FEVER
Authors: Atkins Elisha , Wood W. Barry
Published: June 2004

Further studies have been made of a pyrogenic substance which appears in the circulation of rabbits during the course of experimental fever induced by injection of typhoid vaccine. With the use of a passive transfer method and pyrogen-tolerant recipients, the biological properties of this substance have been differentiated from those of the uncleared vaccine in the circulation. The newly identified factor resembles leucocytic pyrogen in the rapidity with which it produces fever and in its failure to exhibit cross-tolerance with bacterial pyrogen. This striking similarity of properties suggests that the circulating factor is of endogenous origin and may arise from cell injury. A close correlation between its presence in the circulation and the existence of fever has been demonstrated.

The possible relationship of these findings to the pathogenesis of fever is evident.
GROWTH CHARACTERISTICS OF INFLUENZA VIRUS CONCERNING THE BINDING OF VIRUS BY HOST CELLS
Authors: Ackermann W. Wilbur , Ishida Nakao , Maassab H. F.
Published: June 2004

Under certain conditions, influenza virus may bind to chorioallantoic membrane and the infectious property is retained upon prolonged incubation of the complex. Apparently the bound active virus is not functioning in the initiation of viral increase.

The bound infectious virus may be partially removed by extensive washing. The characteristics of the washing are suggestive of a reversible equilibrium type of binding. Binding will also occur when the tissue has been pretreated with RDE or in the presence of AMPS. However, under these conditions the binding is of a lesser degree. When the tissue has been treated with RDE and AMPS is present, no stable binding occurs. In the presence of AMPS, the initiating activity is bound but cannot function in promoting viral increase.

It is proposed that active virus is held by two types of binding at the same site; one type of binding is sensitive to the action of RDE; the second type is sensitive to the blocking effect of AMPS. Virus can be held to the receptor site by either type of binding or both. It is further suggested that the bound infectious virus is a result of an abortive attempt at initiating infection. The nature of the binding of infectious virus is of significance for understanding the binding of initiating activity.
OBSERVATIONS CONCERNING A PERSISTING INFECTION OF HELA CELLS WITH POLIOMYELITIS VIRUS
Authors: Ackermann W. Wilbur , Kurtz Hilda
Published: June 2004

A culture of HeLa cells has been subjected to prolonged observation with the finding that periodically Type III poliomyelitis virus could be isolated from it. A requirement of the culture for survival was the presence in it of serum of certain individuals who had had previous experience with poliomyelitis virus. In the presence of serum containing no antibodies to poliomyelitis virus, the culture demonstrated spontaneous cytopathology. From certain series of passages virus could be isolated while attempts were unsuccessful from others also showing cellular disintegration. The conclusion is reached that the virus does not persist in the culture always in a state exhibiting the infectious property, rather what persists is the potentiality of the culture to give rise to fully active virus. The immune serum could inhibit the cytopathogenic effect of the virus without eliminating the infection.
STUDIES ON THE PATHOGENESIS OF ACUTE INFLAMMATION
Authors: Allison Fred , Smith Mary Ruth , Wood W. Barry
Published: June 2004

The anti-inflammatory action of cortisone upon the acute cellular response to thermal injury has been systematically studied in the rabbit ear chamber. The hormone has been shown to suppress the reaction of acute inflammation in its earliest recognizable phase; i.e., that involving vasodilatation and the adherence of leucocytes to the vascular endothelium. Evidence has been presented that the anti-inflammatory effect of the hormone cannot be explained on the basis of its vasoconstrictive properties alone. The experimental observations support the hypothesis that cortisone exerts a direct protective action upon endothelial cells and leucocytes, and that in so doing, it renders them refractory to the tissue products which initiate inflammation.
EVIDENCE FOR GENETIC INTERACTION BETWEEN NON-INFECTIOUS AND INFECTIOUS INFLUENZA A VIRUSES
Authors: Baron Samuel , Jensen Keith E.
Published: June 2004

Influenza virus rendered non-infectious by ultraviolet irradiation retained ability to "exchange" genetic traits with related virus, resulting in recombined forms. Sedimentation studies indicated association of recombinining activity with particles approximately the size of influenza virus. Genetic activity was not demonstrated when virus was more severely disrupted in attempts to observe phenomena analogous to bacterial transformation. Irradiated virus was also shown to remain capable of genetic exchange for at least 4 days after inoculation into embryonate eggs. In contrast infectious virus becomes insusceptible to genetic exchange after 1 hour incubation in eggs. The importance of this delayed recombination phenomenon to processes of virus evolution and influenza strain variation was discussed.
RED CELL STROMA AND HEMOGLOBIN METABOLISM IN ANEMIC DOGS
Authors: Tishkoff G. H. , Yuile C. L. , Robscheit-Robbins F. S. , Whipple G. H.
Published: June 2004

Red cell stroma protein and hemoglobin can be labeled by feeding C14 lysine during periods of active blood regeneration following anemia.

Stroma proteins are produced and a maximum concentration of the C14 label appears 2 to 3 days earlier than with hemoglobin,—which is to say that stroma building precedes hemoglobin construction.

The concentration of isotope in stroma protein may exceed its concentration in hemoglobin during regeneration following anemia due to blood loss. Diets favorable for hemoglobin regeneration may force the hemoglobin isotope concentration above that of the stroma protein.

In hemolytic anemias great reserves of red cell building material are stored in the body. These stores may modify the curves of isotope concentration in red cells during the recovery periods.

When finally formed, the mature red cells show little or no evidence of participation in general body protein metabolism during their life in the circulation.
FACTORS INFLUENCING HOST-VIRUS INTERACTIONS
Authors: Boring William D. , Angevine D. Murray , Walker Duard L.
Published: June 2004

A study was made of the pathogenesis of infection due to the Conn.-5 strain of Coxsackie virus in 4 to 5 day old infant mice, untreated adult mice, and adult mice treated with cortisone. The quantitative distribution of virus and the evolution of lesions in different tissues were followed for the first 7 days of the infection. Virus dissemination was prompt and widespread via the blood in all groups. In 4 to 5 day old infant mice viral multiplication and cellular injury occurred in many organs and tissues, while in untreated adult mice these processes were largely limited to the pancreas, even though infecting virus appeared to be equally available to other tissues from the blood. Treatment of adult mice with a single injection of 2.5 mg. cortisone resulted in viral multiplication and tissue damage in several sites in addition to the pancreas, the most marked occurring in the liver and heart.

In a consideration of possible mechanisms involved, it was thought unlikely that the differences in the course of the disease in the three groups could be attributed solely to differences in the specific immune response. It is suggested that developmental changes in cells and tissues, perhaps related to cellular metabolism and alterable by cortisone administration, are the major factors determining the location and extent of viral multiplication and tissue injury in this infection in mice.
MITOCHONDRIAL CHANGES INDUCED BY POTASSIUM AND SODIUM IN THE DUODENAL ABSORPTIVE CELL AS STUDIED WITH THE ELECTRON MICROSCOPE
Authors: Weiss Jules M. ,   With Technical Assistance of Doris Fleisch
Published: June 2004

Duodenal absorptive cells from animals fed large amounts of sodium or potassium contain many mitochondria with internal granules. Many mitochondrial granules are also present in cells which transport large amounts of cation. The hypothesis is advanced that the mitochondrial granule represents cation segregated within the mitochondrion. A mechanism is suggested for the segregation of excessive intracellular potassium, and for the transport of cations across cells.
THE PROPERDIN SYSTEM AND IMMUNITY
Authors: Pillemer Louis , Blum Livia , Lepow Irwin H. , Wurz Leona , Todd Earl W.
Published: June 2004

A detailed method for the zymosan assay of properdin is described, together with procedures for the preparation and standardization of reagents employed in the test.

The reliability and reproducibility of the assay, as well as its limitations, are discussed.