bluuebunny/crossref_metadata_2025_split huggingface dataset:
SOME EFFECTS OF PROTEOLYTIC INHIBITORS ON TISSUE INJURY AND SYSTEMIC ANAPHYLAXIS
Authors: Zweifach B. W. , Nagler A. L. , Troll W. 
Published: June 2004

A study was made of the development of various forms of local and systemic injury in animals treated with inhibitors of proteolytic activity. The agents used were tosylarginine methyl ester (TAME), epsilon aminocaproic acid (EACA), and soybean trypsin inhibitor (SBTI).
1. Hemorrhagic necrosis in the skin of the rabbit following intradermal epinephrine in combination with bacterial endotoxin (either intravenous or local) was clearly suppressed by EACA, TAME, and SBTI, given systemically. Tosylarginine (TA) was ineffective.
2. No effect was observed on the classical Shwartzman reaction, the local Arthus phenomenon, or inflammation induced by xylene.
3. The lethal effects of systemic anaphylaxis in the mouse, acute endotoxemia in the rat and mouse, and drum shock in the rat are suppressed by EACA and TAME.
4. There was no effect on the generalized Shwartzman phenomenon in the rabbit and on anaphylaxis in the guinea pig.
5. The effects of EACA or TAME on the injury reactions under investigation were not due to a pharmacological or chemical action on vascular behavior per se.
6. The data provide corroborative evidence for a proteolytic step in injury phenomena which may be mediated through some common activation system.
7. The working hypothesis is advanced that local or systemic stress through the release of epinephrine may result in an increase of a circulating activator of proteolysis and that this in turn may give rise to the release of vasoactive substances,—possibly histamine, serotonin, or a polypeptide.
ANAPHYLAXIS IN CHOPPED GUINEA PIG LUNG
Authors: Austen K. F. , Brocklehurst W. E. 
Published: June 2004

The quantitative release of histamine and slow reacting substance by specific antigen from perfused, chopped, sensitized guinea pig lung has been used to study the opposing effects of monobasic and certain dibasic fatty acids on the anaphylactic reaction.
The anaphylactic release of histamine and slow reacting substance is doubled by the addition of 0.5 mM of succinic or maleic acid to the reaction mixture, and enhancement is definite with as little as 0.05 mM of succinic acid. Prolonged preincubation of the tissue with the dibasic acids is not required, for 60 to 90 per cent of maximal enhancement is apparent when the antigen is added to the tissue only 10 seconds after succinic or maleic acid. The increased histamine release is not due to a qualitative change in the time course of histamine release, is not the result of increased histamine formation, and cannot be attributed to an effect on the tricarboxylic acid cycle. The enhancement seems to be due to potentiation of some step activated by the antigen-antibody interaction and common to both the release of histamine and slow reacting substance. The structural configuration required for a dibasic acid to enhance the anaphylactic reaction in guinea pig lung is quite specific; the carboxyl groups should be separated by a two carbon chain, and must be free or fixed in the cis position.
The monobasic fatty acids from valeric to dodecanoic inhibit the anaphylactic release of histamine, and the concentration needed to produce 50 per cent inhibition decreases with increasing chain length. The introduction of a polar group, amino or carboxyl, into the hydrocarbon residue diminishes or abolishes inhibitory capacity. The inhibition produced by the fatty acids is neither due to calcium binding nor due to prevention of effective antigen-antibody interaction; the fatty acids probably inhibit by acting on an antigen-antibody-activated step.
The inhibition of the anaphylactic release of histamine and slow reacting substance produced by caproic or decanoic acid can be reversed by the enhancing effect of succinic acid, and vice versa. Thus, compounds normally present in mammalian tissue can greatly influence the intensity of the in vitro anaphylactic reaction in the guinea pig.
STUDIES ON HYPERSENSITIVITY
Authors: Gell P. G. H. , Benacerraf B. 
Published: June 2004

In earlier observations with the picryl system, it was concluded that contact sensitivity was a form of delayed (cellular) hypersensitivity to conjugates of sensitizer with autologous proteins indistinguishable in its immunological mechanism from other classical forms of delayed hypersensitivity to proteins. This conclusion has been confirmed and extended with the picryl and chlorbenzoyl chloride systems.
1. It is shown that to induce a state of contact sensitivity, the minimal necessary amounts of hapten are of the same order of magnitude, whether this hapten is conjugated with protein or the free reactive chemical itself. From this, it is evident that contamination of conjugates with small amounts of unreacted sensitizer plays no part in the induction of contact reactivity by the conjugate. With the dinitrophenyl system, no contact sensitivity could be induced by the conjugates used; possible reasons for this discrepancy are discussed.
2. Animals sensitized to contact by homologous conjugate can be completely desensitized by injections of such a conjugate in large amount; a similar injection schedule has no effect on the contact sensitivity of animals sensitized with the free reactive sensitizer.
3. The capacity of heterologous (ovalbumin) conjugates to evoke anti-hapten antibodies is shown to be greater than that of homologous (guinea pig seralbumin) conjugates: the reverse is true of their capacity to induce delayed reactivity.
4. Evidence is brought forward to suggest that in animals sensitized with homologous albumin conjugates, the specificity of the delayed reaction involves more than the hapten alone, even though the carrier protein is non-antigenic on its own. The contrast with the apparent lesser specificity of the antibodies later produced is discussed.
STUDIES ON THE PATHOGENESIS OF STAPHYLOCOCCAL INFECTION
Authors: Conti Charles R. , Cluff Leighton E. , Scheder E. Patricia 
Published: June 2004

Intracutaneous and intravenous injection of pyrogenic, non-lethal doses of bacterial endotoxin were found to increase the infectivity of pathogenic but not non-pathogenic staphylococci in rabbit skin. The increased infectivity of the microorganism was characterized by accelerated multiplication at the site of inoculation and by the production of necrosis and hemorrhage locally. Histologically, the infection of skin in endotoxin-prepared animals was characterized by necrosis, masses of bacteria, but absence of leukocytic infiltration into the area of bacterial growth.
The infectivity of staphylococci in skin of endotoxin-prepared rabbits could be controlled by antibody to the alpha hemolysin of the microorganism.
The effect of endotoxin upon staphylococcal infection was demonstrable only within 4 hours after injection of the endotoxin. It could not be prevented with chlorpromazine or dibenamine and was closely related to the effect of endotoxin upon leukocytes.
It was suggested that the effect of endotoxin upon leukocytes was probably responsible for its influence upon staphylococcal infection.
The implications of these findings in the pathogenesis of staphylococcal infection are discussed.
OCCURRENCE OF FOCAL THREE-DIMENSIONAL PROLIFERATION IN CULTURED HUMAN CELLS AFTER PROLONGED INFECTION WITH HERPES SIMPLEX VIRUS
Authors: Hinze Harry C. , Walker Duard L. 
Published: June 2004

The occurrence of focal three-dimensional proliferation was observed in human conjunctiva cells in culture after prolonged infection with herpes simplex virus at 30°C. and in KB cells infected with herpes virus at 37°C. for several months in the presence of pooled human serum. This atypical growth pattern consisted of many discrete piles of cells 15 to 20 cells thick scattered over a monolayer of cells.
Three-dimensional growth appeared only in the presence of 10 to 20 per cent of selected human sera. When horse serum was substituted for human serum growth was in an ordinary monolayer.
The abnormal growth pattern of this cell line (C-4 line) has remained stable through continuous culture for over 2 years and was observed consistently in each of 25 clones isolated from the parent culture.
Repeated tests for the presence of persisting infectious virus and for herpes virus antigen in the cells were negative.
Comparison of the C-4 cell line with control conjunctiva cells revealed no significant difference in multiplication rate or in range of viral susceptibility, but the C-4 line was found to be more sensitive to ultraviolet irradiation.
STUDIES ON FLUORESCENT ANTIBODY STAINING
Authors: Goldstein Gerald , Slizys Irene S. , Chase Merrill W. 
Published: June 2004

1. A study has been made of the non-specific fluorescent staining of splenic imprints treated with fluorescent sheep antibody globulins.
2. In tissue imprints made with the spleens of antigen-stimulated animals, no morphological distinction was evident between areas showing non-specific fluorescence and specific fluorescence.
3. Elimination of non-specific fluorescence was not achieved by any one, or any combination of the following: (a) conjugating only gamma globulins with fluorescein isothiocyanate; (b) removal of dialyzable fluorescent products on sephadex, followed by concentration through the use of pressure dialysis; (c) use of crystalline preparations of fluorescein isothiocyanate.
4. Individual preparations of fluorescent antibodies were separated by gradient elution chromatography on diethylaminoethyl (DEAE) cellulose into fractions possessing different numbers of fluorescein radicals per molecule of globulin.
5. The coupling ratio of 50 mg fluorescein isothiocyanate (FITC) per gm of protein, as commonly advocated, can not be recommended for the precise localization of antibody globulin in tissues owing to the capacity of the coupled products to give non-specific fluorescent staining. When crystalline preparations of FITC are used instead of the amorphous product at 50 mg/gm protein, far too high non-specific fluorescence results.
6. A fraction with bright specific fluorescence and no or negligible nonspecific fluorescence was obtained from each fluorescent antibody that was prepared by using 6 to 8 mg of crystalline fluorescein isothiocyanate per gm of globulin and was then subjected to DEAE-cellulose chromatography and gradient elution to eliminate the most highly coupled molecules.
CHANGES IN CONNECTIVE TISSUE AND INTESTINE CAUSED BY VITAMIN A IN AMPHIBIA, AND THEIR ACCELERATION BY HYDROCORTISONE
Authors: Weissmann Gerald 
Published: June 2004

In view of the theory that an excess of vitamin A causes release of cathepsins from intracellular lysosomes, hypervitaminosis A was induced orally in the larvae of Xenopus laevis. It was predicted that the tails of these amphibia would undergo resorption prior to metamorphosis, since the presence of abundant lysosomes, associated with measurable increases of catheptic activity, had previously been demonstrated in the resorbing tails of amphibia during metamorphosis. This prediction was confirmed; after 3 to 4 weeks of hypervitaminosis A, the tails of treated animals underwent partial resorption.
Other transitory appendages, the rostral tentacles, collapsed after 2 weeks of treatment with an excess of vitamin A, an effect analogous to the collapse of rabbits' ears after intravenous papain. These effects were related to the loss of metachromatic extracellular material in these appendages. Excess of vitamin A caused kyphoscoliosis and prognathos in the larvae.
The hypervitaminotic larvae always developed a mucinous diarrhea, which was associated with a remarkable overgrowth of metachromatic goblet cells of the intestine. The entire intestine of the treated animals was more advanced in development than that of control larvae at equivalent stages.
All the effects of hypervitaminosis A were accelerated by the simultaneous administration of hydrocortisone. This was held to be due to liberation of vitamin A from hepatic stores by the steroid, and is in contrast to the retardation of hypervitaminosis A by hydrocortisone in vitro.
INVOLVEMENT OF ADRENERGIC FACTORS IN THE EFFECTS OF BACTERIAL ENDOTOXIN
Authors: Gourzis James T. , Hollenberg Murray W. , Nickerson Mark 
Published: June 2004

The possible involvement of adrenergic mechanisms in the effects of Escherichia coli endotoxin was investigated in several preparations. Appropriate pretreatment of rabbits with E. coli endotoxin significantly increased pressor responses to epinephrine and norepinephrine as compared to untreated controls. Exposure of isolated rabbit aorta strips to E. coli endotoxin in a medium containing whole blood or cellular constituents of blood significantly increased the response to epinephrine. Endotoxin had no effect on responses to epinephrine in ritro when plain Krebs-Ringer solution was used.
Pretreatment with reserpine or phenoxybenzamine (dibenzyline) protected rabbits and mice against the acute lethal effects of E. coli endotoxin. The time period intervening between reserpine or dibenzyline administration and challenge by endotoxin precluded a direct antiendotoxic action of these agents. In addition, incubation of dibenzyline with endotoxin in vitro, under conditions which would favor reaction, did not decrease the toxicity of the latter.
These results indicate that peripheral adrenergic mechanisms are intimately involved in the effects of E. coli endotoxin and support the concept that deleterious effects of endotoxin in shock probably are due to exaggeration of existing vasoconstriction in an already compromised organism.
FURTHER CHARACTERIZATION OF THE ADENOVIRUS ERYTHROCYTE RECEPTOR-MODIFYING FACTOR
Authors: Kasel Julius A. , Rowe Wallace P. , Nemes John L. 
Published: June 2004

Agglutinability of human erythrocytes for 3 hemagglutinating adenoviruses was markedly reduced by pretreatment of red cells with a factor present in tissue cultures which had been infected with adenovirus types 1, 2,4, or 15.
The factor responsible for erythrocyte receptor modification was non-dialyzable and unaffected by the action of ribonuclease, desoxyribonuclease, trypsin, chymotrypsin, or ether. The factor was smaller, more thermostable, and separable from the infectious virus.
Erythrocyte receptor modification was found to be a function of time and temperature. Titers of erythrocyte receptor-modifying activity were not diminished by successive exposures to fresh erythrocytes. Erythrocytes treated with erythrocyte receptor-modifying factor suspensions failed to significantly adsorb test virus hemagglutinin.
Inhibition of erythrocyte receptor modifying-activity of the adenovirus suspensions by rabbit antiserum was type-specific.
SELECTIVE ADRENAL NECROSIS AND APOPLEXY INDUCED BY 7,12-DIMETHYLBENZ(a)ANTHRACENE
Authors: Huggins Charles , Morii Sotokichi 
Published: June 2004

Invariably in every normal rat a single dose of 7, 12-dimethylbenz(a)anthracene, by mouth or injected in a vein, was found to cause apoplexy and massive necrosis in the inner zones of the adrenal cortex; the zona glomerulosa, the adrenal medulla, and a small region of cortex adjacent to the great adrenal vessels were spared from damage. DMBA caused these selective lesions in females and in males of 2 strains of rats. Hemorrhage and necrosis were observed in no organ other than the adrenal gland. Whereas adrenal glands were heavily damaged by DMBA, pituitary and ovary escaped injury by the compound.
A single huge but sublethal feeding of o, p'-DDD caused degenerative changes of minor magnitude in the adrenals and only in a small percentage of rats; the property of inducing adrenal damage was not shared by other polynuclear aromatic hydrocarbons which were investigated, including strong carcinogens.
Presence of adrenal medulla is not a prerequisite to damage of the adrenal cortex by DMBA. The adrenal damage occurred in rats, given DMBA, from which the pituitary had been removed but the lesions were smaller in extent and less in incidence as post-hypophysectomy atrophy of the adrenal cortex progressed.
The entire DMBA molecule was necessary to induce adrenal damage; fragments of this molecule did not induce adrenal lesions. Two components which are of cardinal importance in this specific damaging effect are: (a) electronic factor; (b) steric factor.
The level of isocitric dehydrogenase in adrenal is modified considerably by presence or absence of estradiol-17ß.
OBSERVATIONS ON THE FINE STRUCTURE OF MATURE HERPES SIMPLEX VIRUS AND ON THE COMPOSITION OF ITS NUCLEOID
Authors: Epstein M. A. 
Published: June 2004

The fine structure and composition of mature herpes virus have been investigated in thin sections by electron microscopy. The virus was grown in cultured HeLa cells and was collected with them. Tests for the biological activity of the infected cultures were included in the first half of the work. Preparations were fixed with both osmium and permanganate, and were embedded either in methacrylate or in aquon, a water-miscible fraction of a commercially available epoxy resin. In further experiments material fixed with permanganate was subjected to the action of specific nucleases or control medium before embedding.
All the preparations showed numerous uniform particles around and between the cells and this was paralleled by considerable biological activity where tests were made on samples of the culture fluids.
Mature herpes virus has been found to be round and to measure, when dehydration shrinkage is avoided, about 165 mµ in diameter. The particle contained an eccentric round-ended rod-shaped, electron-opaque nucleoid lying in an inner zone of low density. A dense outer zone or viroplasm surrounded this, no membrane being present between the two zones. After permanganate fixation the particle was found to have an outer limiting membrane showing a triple-layered structure morphologically indistinguishable from that of the plasma membrane of the HeLa cells.
The results of the digestion experiments show that herpes virus contains nucleic acid of deoxyribose type and that this is localized in the dense nucleoid.
Both the findings and the methods used are discussed.
CRITICAL RELATIONSHIPS BETWEEN CONSTITUENTS OF THE ANTIGEN-ADJUVANT EMULSION AFFECTING EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS IN A COMPLETELY SUSCEPTIBLE MOUSE GENOTYPE
Authors: Lee Johanna M. , Schneider Howard A. 
Published: June 2004

The production of EAE in the fully susceptible BSVS mouse genotype has been found to be dependent on the ratio of proteolipid antigen and adjuvant mycobacterial concentration as used in the emulsion, of the Freund type. Disturbance of this ratio, by manipulation of either component, by diminution or increase, results in a decrease in the frequency by which EAE is produced.
Simultaneous reduction of antigen and mycobacteria, so that the ratio remains unchanged, retains the full EAE-producing power of the emulsion. The limit of this has not been ascertained.
Emulsifying agents have been found to restrict further the permissible limits of the antigen-mycobacterial ratio for full EAE production. Such effects of the emulsifier have been found to vary with the qualitative nature of the emulsifier. Aquaphor has been found to be less restrictive than falba.
These phenomena, systematically analyzed here for the mouse, may have an application for other antigen-adjuvant systems and for other hosts.
THE CHEMOTACTIC EFFECT OF MIXTURES OF ANTIBODY AND ANTIGEN ON POLYMORPHONUCLEAR LEUCOCYTES
Authors: Boyden Stephen 
Published: June 2004

An in vitro technique is described for assessing the chemotactic activity of soluble substances on motile cells.
Antibody-antigen mixtures when incubated (37°C) in medium containing fresh (i.e. non-inactivated) normal rabbit serum exert a strong chemotactic effect on rabbit polymorphonuclear leucocytes.
Results are described which indicate that, when antibody-antigen complexes are incubated (37°C) in fresh serum, a heat-stable (56°C) substance (or substances) is produced which acts directly as a chemotactic stimulus on the polymorphs. This heat-stable chemotactic substance is not produced when antibody-antigen complexes are incubated in serum which has been heated at 56°C for 30 minutes.
STUDIES ON TUBERCLE BACILLUS-HISTIOCYTE RELATIONSHIP
Authors: Fong Jacob , Chin Dennis , Elberg Sanford S. 
Published: June 2004

Studies of passive transfer of cellular resistance, as manifested by refractoriness to necrotization with virulent tubercle bacilli, have shown that immune histiocytes or immune lymphocytes were effective transferring agents; immune polymorphonuclear leucocytes and immune serum as well as comparable cells from normal animals lacked this capacity.
Comparisons of immune histiocytes and immune lymphocytes showed that the former cells were more efficient; this was indicated by (a) the smaller numbers of immune histiocytes needed for passive transfer, (b) the longer duration of cellular resistance in recipients given histiocytes than in those given lymphocytes, (c) the greater capacity of histiocytes to effect serial passive transfer, and (d) the ability of histiocytic but not lymphocytic lysates to transfer cellular resistance.
Experiments to establish the mechanism of passive transfer of cellular resistance showed that there was no active induction of resistance in recipients through transfer of bacillary antigens contained in immune histiocytes; in fact, the results of serial passive transfers with immune histiocytes suggested an active replication of the "cell resistance factor."
CYTOMETRIC ASSAY OF TOXICITY OF BRUCELLA ANTIGENS FOR SENSITIZED AND NON-SENSITIZED CELLS FROM THE GUINEA PIG
Authors: Carpenter Charles M. , Fukuda Morimichi , Heiskell Charles L. 
Published: June 2004

1. A significant cytotoxic effect of trypsinized, sensitized cell cultures was observed when re-exposed to Brucella antigens in vitro.
2. The cytometric assay of the toxic effects of Brucella antigens using trypsinized cells from sensitized animals provides an objective measure of induced cellular hypersensitivity.
AN ALUMINUM MARKER FOR THE DIFFERENTIATION AND SEPARATION OF VIRULENT AND ATTENUATED POLIOVIRUSES
Authors: Wallis Craig , Melnick Joseph L. , Ferry George D. , Wimberly Ira L. 
Published: June 2004

A new character, the A marker, for polioviruses is described. In the presence of Al+++ (1 to 100 mM) attenuated, but not virulent, strains of type 1 and type 2 polioviruses are stabilized so that they resist thermal inactivation at 50°C. Differences between the attenuated and virulent type 3 strains studied were of the opposite character and less marked.
By the use of optimal concentrations of Al+++ (12 mM for type 1 and 1 mM for type 2) attenuated strains can be separated from mixtures containing virulent type 1 or 2 strains.
The A marker was found to be correlated with the d but not the rct/40 or T marker. The A marker has been used for following genetic changes of vaccine strains after their multiplication in man.