bluuebunny/crossref_metadata_2025_split huggingface dataset:
EFFECTS OF BACTERIAL ENDOTOXINS ON METABOLISM
Authors: Berry L. Joe , Smythe Dorothy S. 
Published: June 2004

Cortisone is known to protect mice against the lethal effects of endotoxin. It also elevates liver tryptophan pyrrolase (TP) activity, an enzyme that converts tryptophan into an intermediate which, in turn, is transformed in a series of reactions into nicotinamide, a component of the pyridine nucleotides. In the present report, results of experiments attempting to link the prophylactic action of cortisone in endointoxication to metabolism of tryptophan are described. It was shown first that both nicotinamide and diphosphopyridine nucleotide (DPN), compounds along the pathway initiated by TP, are each as effective as cortisone in protecting mice against lethality of different amounts of endotoxin. L-Tryptophan, which alone results in an increase in liver TP, fails to protect against endotoxin when it is given either 4 hours before or concurrently with the toxin while it potentiates the toxin when administered 4 hours later. Cortisone, nicotinamide, and DPN all fail to protect mice against lethality when given 4 hours after endotoxin but they do not potentiate it as does tryptophan.
Additional evidence linking tryptophan metabolism to endotoxin poisoning was derived from assays for TP. Activity of the enzyme in livers of mice 17 hours after injecting an LD50 of endotoxin is less than one-half the control value. It remains below normal for 48 hours. In adrenalectomized mice, TP activity is about the same as in mice 17 hours after endotoxin. Animals protected against lethality of endotoxin by cortisone have normal levels of TP but if the cortisone is given 4 hours after the toxin, TP activity is the same as in mice given endotoxin alone. Tryptophan is unable to maintain a normal level of TP when it is given concurrently with endotoxin. TP activity is not depressed when mice made tolerant to endotoxin are given an injection of endotoxin at the LD50 level for normal animals. Normal activity of the enzyme was always observed in livers of mice protected against endotoxin but not in those where protection failed.
The total amount of oxidized pyridine nucleotides (PN+) in livers of mice 17 hours after an LD60 of endotoxin is about two-thirds the normal level. Animals injected with either cortisone or nicotinamide at the same time as endotoxin maintain the PN+ level in liver.
Mice exposed to 5°C during the postinjection period can be protected with cortisone or nicotinamide against lethality of endotoxin but not with DPN. Changes in TP activity do not parallel those found in mice kept at 25°C. The toxic manifestations of endotoxin appear to be different, therefore, in animals stressed by cold.
EFFECTS OF CHRONIC EXCESS SALT INGESTION
Authors: Dahl Lewis K. , Heine Martha , Tassinari Lorraine 
Published: June 2004

By selective inbreeding, two strains of rats were developed previously that differed markedly in their susceptibility to the development of experimental hypertension from excess salt ingestion (1, 2). The present report indicates that with animals derived from the same strains, similar differences in response were obtained in rats subjected to either combined desoxycorticosterone-NaCl (DOCA-salt) treatment or unilateral renal artery compression without extra dietary salt. Thus differences in genetic substrate appear to influence the development of experimental hypertension produced by these three techniques and possibly this may hold true for all "varieties" of experimental hypertension. If true, it might allow the development of a unifying hypothesis that could be relevant not only to experimental hypertension but perhaps to human hypertension as well.
The DOCA-salt regimen was more toxic to the animals than unilateral renal artery compression. Tentatively, this was ascribed to either, or both, the younger age or the higher NaCl intake of the animals in the former.
OXYGEN-STABLE HEMOLYSINS OF GROUP A STREPTOCOCCI
Authors: Ginsburg Isaac , Harris T. N. , Grossowicz Nathan 
Published: June 2004

The production of oxygen-stable hemolysin in growing and resting Group A streptococci has been induced by RNA, by detergents, and by mammalian blood serum proteins, in the presence of glucose, Mg++, and cysteine. Of the serum proteins, albumin and α lipoprotein could act as inducers. In the case of both these serum proteins treatment with trypsin did not affect the capacity to induce hemolysin production, but removal of the bound lipids by alcohol-ether or chloroform-methanol destroyed this property.
In comparisons of the conditions of production and of activity between the hemolysin produced by RNA on one hand and albumin and detergents on the other, some data indicated similarities among the hemolysins, and others, differences. The similarities included similar degrees of temperature dependence for production and equal degrees of inhibition by serum ß lipoprotein. Differences found among these hemolysins included differences between, the rate of production of the RNA hemolysin from that of albumin or detergent hemolysin by both resting and growing streptococci, and the failure of utilization of glucosamine as an energy source for the production of albumin hemolysin, in contrast with that of RNA hemolysin. The fact that the data have in some cases indicated similarities and in other cases differences among the hemolysins raises the question of whether these are different molecular species, or a single hemolysin synthesized by the streptococci via different pathways of metabolism, or complexes of a single hemolytic moiety with various molecular carriers.
OXYGEN-STABLE HEMOLYSINS OF GROUP A STREPTOCOCCI
Authors: Ginsburg Isaac , Harris T. N. 
Published: June 2004

The oxygen-stable streptococcal hemolysins, which can be induced by a number of diverse substances, have been studied. Differences among these hemolysins have been found in electrophoresis, chromatography, pH stability, and susceptibility to some organic solvents and to an enzyme, RNAase. These properties have in each case been found to characterize the inducing substances as well.
In a number of instances it has been found possible to incubate one inducer with the hemolysin induced by another of these agents and then, after appropriate fractionation, to find hemolytic activity in the fraction containing the fresh inducer. These observations suggest that the oxygen-stable streptococcal hemolysins are constituted as carrier-hemolysin complexes, the carriers being the set of molecular species effective as inducers, and the prosthetic group being transferred from one carrier to another under appropriate conditions.
After transfer of the hemolytic moiety from a hemolysin molecule which is susceptible to inactivation by a given agent or set of conditions to a carrier which is not itself significantly affected by this agent, the new, derived, hemolysin has been found not to be inactivated by the agent. The hemolysins of this group can thus be inactivated by enzymatic attack on the prosthetic group, or by hydrolysis or deformation of the postulated carrier molecule.
THE FORMATION AND PROPERTIES OF POLIOVIRUS-NEUTRALIZING ANTIBODY
Authors: Svehag Sven-Eric , Mandel Benjamin 
Published: June 2004

Transient 19S antibody formation was induced in rabbits by single or repeated stimuli with a small dose of poliovirus. Available evidence indicated that cessation of 19S synthesis was due to lack of continuous antigenic stimulation and not to loss of cells participating in antibody formation. "Immunological memory" in 19S antibody formation was demonstrable only within 2 to 3 days following discontinuation of synthesis but not thereafter.
Following stimulation with a high dose of polio-virus both 19S and 7S antibodies were formed. The kinetics of their formation differed in several respects: (a) 19S antibody preceded 7S antibody by ⩾1½ days; (b) 19S antibody rose to peak titers at a rapid exponential rate within 1 week, while 7S antibody increased at a slow decelerating rate for ⩽3 weeks; (c) 19S antibody formation was short-lasting while 7S antibody synthesis endured. A renewed formation of both antibodies occurred following restimulation with a high antigen dose. The secondary 19S and 7S antibody responses were similar to the respective primary responses, and the preexistence of 7S antibody synthesis did not detectably alter the secondary 19S response.
Both 19S and 7S antibodies were formed and the kinetics of their formation was similar (a) for infectious and non-infectious (UV-) poliovirus antigen; (b) for the serologically unrelated poliovirus and Coxsackie B-4 virus; (c) when poliovirus was administered by different routes; (d) when 1-day-old or adult rabbits were immunized; (e) in antibody responses to poliovirus in rabbit, guinea pig, and man.
Whole body x-irradiation 20 hours prior to antigenic stimulus (high dose) resulted in delayed but markedly prolonged 19S antibody formation and inhibition of 7S antibody synthesis.
Thus, the formation of 19S and 7S antibody differed in (a) antigen dose requirements for induction and maintained synthesis; (b) kinetics; (c) retention of memory; and (d) sensitivity to prior x-irradiation. These differences are best explained on the assumption that the two antibodies are produced by different cells.
IMMUNOLOGIC INCOMPETENCE OF IMMUNOLOGICALLY RUNTED ANIMALS
Authors: Blaese R. Michael , Martinez Carlos , Good Robert A. 
Published: June 2004

1. Adult (A x C57Bl/1)F1 hybrids regularly show runt disease when injected with adult spleen cells from A strain donors. This also occurs when A strain spleen cells are administered to adult C3H mice made tolerant of A strain tissue in the neonatal period.
2. Mice undergoing the graft versus host reaction fail to form antibodies to an intraperitoneal challenge of T2 bacteriophage. This phenomenon was observed well before any of the other overt signs of runting had occurred. Further, inhibition of antibody production to T2 phage by graft versus host reaction initiated at an interval following antigenic stimulation is demonstrated.
3. The basis for the immunologic incompetence of the host with respect to T2 phage is presumed to be the attack of immunologically competent donor cells on the lymphoid cells of the recipient.
4. The failure of the injected parent strain cells to respond to the antigen used may imply immunologic commitment of these cells.
MECHANISMS OF ENDOTOXIN TOLERANCE
Authors: Greisman Sheldon E. , Wagner Henry N. , Iio Masahiro , Hornick Richard B. 
Published: June 2004

Healthy male volunteers were rendered tolerant to the pyrogenic and toxic activities of bacterial endotoxin by daily intravenous injections. Five subjects were given 0.5 µg Salmonella typhosa endotoxin for 7 days; four subjects were given Pseudomonas endotoxin, increasing over a period of 30 days from 25 to 250 µg. Reticuloendothelial system (RES) phagocytic activity was assessed by serial measurements of the clearance of I131-labeled aggregated human serum albumin. In no subject was an increase in RES phagocytic activity detectable. Such negative findings could not be attributed to decreased RES blood flow.—Additional studies on the pyrogenic responses of man to various schedules of endotoxin administration revealed: (a) Hyperreactivity of some subjects to a second injection of endotoxin administered 24 hours after the initial dose; (b) prevention of such hyperreactivity by plasma from donors tolerant to a heterologous endotoxin, but not from normal donors; (c) reduced reactivity to a second injection of endotoxin given 7 days after the initial dose; (d) reversal of induced tolerance by administration of half the dose of endotoxin followed 2 hours later by the second half; (e) reversal of induced tolerance 24 hours after administration of a heterologous endotoxin; (f) enhanced dermal reactivity to endotoxin induced inflammation during tolerance.
The observations are consistent with the hypothesis that tolerance to the pyrogenic activity of endotoxin in man is not based upon generalized enhancement of RES phagocytic activity or exhaustion of host reactivity but rather involves the participation of specific antibody which assists the RES in the clearance and inactivation of the endotoxin molecule.
THE COURSE OF EXPERIMENTAL AUTOALLERGIC THYROIDITIS IN INBRED GUINEA PIGS
Authors: Lerner Edwin M. , McMaster Philip R. B. , Exum Eurmal D. 
Published: June 2004

Experimental allergic thyroiditis produced in strain 13 histocompatible guinea pigs after a single immunization with thyroid extract and Freund's adjuvant was followed for more than 2 years. The disease appeared as early as 5 days and persisted for the entire period studied, although it regressed in the later stages.
Circulating antithyroid antibody was detected at low levels as early as 7 days after immunization, and increased to a peak at the time of most severe disease. Thereafter, antibody decreased, but was still detectable in most animals as late as 2 years. There was no correlation between antibody levels and extent of disease except at the 7 week stage.
Delayed sensitivity to thyroid antigen was found as early as 5 days after immunization, and appeared to precede the development of thyroiditis in many animals. It correlated closely with thyroiditis at 5 days and 7 weeks. At 6 months, the delayed skin reaction was decreased, and a modified type of reaction appeared which persisted as long as 26 months.
The time relationship of delayed sensitivity, thyroiditis, and circulating antibody continue to confirm the role of delayed sensitivity in the pathogenesis of this disease. The accumulated data demonstrating production of thyroiditis without antibody, and the converse, tend to strengthen this view.
THE PATHOGENESIS OF HERPES VIRUS ENCEPHALITIS
Authors: Johnson Richard T. 
Published: June 2004

The pathogenesis of herpes simplex virus encephalitis and myelitis was studied in suckling mice using routine titration procedures and fluorescent antibody staining for the identification of infected cells. After intracerebral inoculation virus was shown to disperse rapidly in the cerebrospinal fluid (CSF), multiply in meninges and ependyma, and then invade the underlying parenchyma infecting both neurons and glia.
Following extraneural inoculation virus gained access to the central nervous system (CNS) by both hematogenous and neural pathways. After intraperitoneal and intranasal inoculation virus was found to multiply in viscera and produce viremia; foci of CNS infection then developed around small cerebral vessels.
After subcutaneous and intranasal inoculation neural spread of virus was demonstrated along corresponding peripheral and cranial nerves. This spread resulted from the centripetal infection of endoneural cells (Schwann cells and fibroblasts). Antigen was not found in axons even after infection of the corresponding ganglion cell perikaryon. Subsequent spread within the CNS was unrelated to neural tracts, and there was no evidence of axonal spread of virus in the host-virus system studied.
These findings are discussed in relation to previous and current theories of the viral "blood-brain barrier" and neural pathways of infection.
ANALYSIS OF THE EXPERIMENTAL LESION OF CONNECTIVE TISSUE PRODUCED BY A COMPLEX OF C POLYSACCHARIDE FROM GROUP A STREPTOCOCCI
Authors: Schwab John H. 
Published: June 2004

Rabbits presumably sensitized to components of the streptococcal cell by natural contact with cross-reactive microbial antigens in their environment, display distinctive phases of evolving allergic response to an extract of streptococcal cells. Animals under 4 weeks of age show no gross allergic skin reaction; this is followed successively by age periods in which allergic reactions become most prominent at 4 hours, 23 hours, or 2 to 4 days after injection.
A relapsing nodular lesion, produced by cell wall components in the cell extract, occurs in neonatal rabbits which display no hypersensitivity, reaches a peak response in young animals during the period of most active growth, and decreases in severity in older rabbits while the degree of hypersensitivity is increasing. Relapses occur with greater frequency in neonatal than in older rabbits. Passive transfer of spleen cells or serum from sensitized adult rabbits has no influence on the nodular reaction in neonatal animals.
THE FORMATION AND PROPERTIES OF POLIOVIRUS-NEUTRALIZING ANTIBODY
Authors: Svehag Sven-Eric 
Published: June 2004

Rabbit sera were found to possess neutralizing activity (normal antibody) to polioviruses and Coxsackie B viruses. This normal antibody showed high specificity in cross-neutralization and absorption tests. It was associated with heat-stable, mercaptan-sensitive, 19S γ1-ß-macroglobulins, which formed weak complexes with the viral antigen. In rare instances, sera with normal macroglobulin antibody, also contained very low activity which was due to 7S γ2-globulins. The neutralization of poliovirus by normal 19S γ1-ß-antibody appeared to follow first order kinetics, and the thermodynamic parameters of this reaction were the same as those of serological reactions employing immune antibody.
The electrophoretic mobility, sedimentation properties, sensitivity to mercaptan, thermostability, and avidity of normal and early (up to day 3) immune antibodies to poliovirus were similar, but differed in several respects from those of late immune antibodies. Thus, the available evidence suggested, that earlier reported differences between normal and immune antibodies reflected differences between antibodies of diverse physicochemical properties rather than between normal and immune antibodies per se.
It is proposed that the normal macroglobulin antibody is associated with an immunological response to repeated stimulation with minute amounts of antigen.
IMMUNOLOGIC RELATION OF STREPTOCOCCAL AND TISSUE ANTIGENS
Authors: Kaplan Melvin H. , Svec Kathryn H. 
Published: June 2004

Sera from patients with recent streptococcal infection or non-suppurative sequelae exhibit with variable frequency a precipitin reaction in agar gel with a partially purified streptococcal antigen which has been shown previously to be immunologically related to human heart tissue. This precipitin could be absorbed from sera with normal human heart tissue homogenates but not with homogenates of other organs. Demonstration of this cross-reaction by heart absorption was found dependent both upon the serologic properties of individual sera and the nature or state of purification of the streptococcal product employed as test antigen. Evidence was obtained of a close association of heart-related and non-heart-related antigenic determinants in partially purified preparations of the streptococcal antigen by both gel diffusion and immunoelectrophoresis. On immunoelectrophoretic analysis, cross-reactive antigen exhibited a more rapid mobility toward the anode than M protein. It was destroyed by digestion with trypsin, pepsin, and chymotrypsin. Based on specific absorption tests with a Type 5 and Type 19 strain, the antigen was localized to cell walls and to a lesser extent to cell membranes of these strains.
Precipitating activity related to cross-reactive antibody was localized to the immunoglobulin zone in immunoelectrophoresis. Reactive sera showed diminution or loss of serological activity following heat inactivation at 56°C or after prolonged storage at 4°C. Sera containing cross-reactive precipitating antibody exhibited an immunofluorescent reaction with sarcolemma of cardiac myofibers, which was inhibited by streptococcal cross-reactive antigen. By this inhibition test, the immunofluorescent reaction related to cross-reactive antibody could be distinguished from that due to other heart-reactive factors.
Antibody to streptococcal cross-reactive antigen defined by precipitation-absorption tests was observed in 24 per cent of patients with recent history of uncomplicated streptococcal infection and in the majority of patients with acute rheumatic fever, rheumatic heart disease, or acute glomerulonephritis. It was observed rarely in patients with non-streptococcal related disease. These data provide evidence that induction of cross-reactive autoantibody to heart in certain individuals is associated with streptococcal infection.
STUDIES ON THE PATHOGENESIS OF FEVER
Authors: Berlin Richard D. , Wood W. Barry 
Published: June 2004

The metabolic reactions responsible for the release of endogenous pyrogen from rabbit granulocytes incubated in 0.15 M NaCl are specifically inhibited by the presence of K+ (and by related alkali metal ions, Rb+ and Cs+) in the medium. The inhibitory action of K+ apparently involves penetration of the cell membrane and is directly antagonized by the cardiac glycoside, ouabain. It is concluded, therefore, that the inhibition of pyrogen release by extracellular K+ is due to transport of K+ into the cell.
Although the precise molecular mechanisms which are responsible for the release of pyrogen from granulocytes incubated in K-free saline have not been elucidated, further study of the process has revealed: (a) that it is preceded by the accumulation of pyrogen within the cell, (b) that it depends upon the catalytic action of one or more sulfhydryl-containing enzymes, (c) that it does not require energy, either from glycolysis or from reactions depending on molecular oxygen, and (d) that its inhibition by K+ and by arsenite is qualitatively similar to the depression caused by these same reagents on the release of other leucocytic proteins; i.e., lysozyme and aldolase.
PROTEIN-PROTEIN INTERACTIONS AMONG L POLYPEPTIDE CHAINS OF BENCE-JONES PROTEINS AND HUMAN γ-GLOBULINS
Authors: Gally J. A. , Edelman G. M. 
Published: June 2004

The L polypeptide chains of certain Bence-Jones proteins of group I have been found in three forms: monomers of molecular weight of about 20,000, dimers which monomerize in dissociating solvents, and dimers which are stable in such solvents. The L polypeptide chains of some Bence-Jones proteins of group II were found to occur naturally only as stable dimers. The L chains of normal human γ-globulin have been obtained in a reduced unalkylated form, and a fraction of these chains was found to form stable dimers under oxidizing conditions. It is suggested that a single disulfide bond is involved in stabilization of the dimer.
In experiments on the reconstitution of 7S γ-globulin, it was found that stable dimers of L polypeptide chains did not associate appreciably with Hγ chains to form a soluble product. L chains in the monomeric form, both of a reduced alkylated Bence-Jones protein and of reduced unalkylated γ-globulin, combined with Hγ chains to form a 7S product. After hydrolysis with papain, the 7S material containing the Bence-Jones L chains yielded fragments comparable to the fragments of papain-treated myeloma proteins.
As indicated by spectrofluorometric measurements, dissociable dimers and stable dimers of the L chains of a Bence-Jones protein both underwent identical thermally induced transitions in the temperature range 48–58°C. When L polypeptide chains were present in reduced alkylated γ-globulin or reduced alkylated S fragments, no transition occurred until 65°C, the coagulation temperature of γ-globulin and S fragments. Above this temperature, L chains were released into solution. These experiments suggested that free L chains and L chains bound to Hγ chains have different conformational stabilities.