bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of Persistent Modoc Viral Infections in Syrian Hamsters
Authors: Davis James W. , Hardy James L.
Published: January 2020

Adult Syrian hamsters were readily infected by intranasal inoculation with Modoc virus. Viremias were detected 2 to 6 days after infection and peak viremia titers (10
6.2
plaque-forming units/ml of blood) occurred 4 days postinoculation. All infected animals developed neutralizing and hemagglutination-inhibiting antibodies by 7 days, and complement-fixing antibodies by 14 days postinoculation. High titers of antibodies persisted for at least 4 months. Modoc virus was recovered from throat swabs at 7 days postinoculation, but not at 14 days or later. Urine samples were positive for virus throughout a 12-week observation period. Isolation of virus from lungs and kidneys of one and three animals, respectively, at 151 to 221 days after inoculation confirmed chronic infection. Viral isolations were made only when organs were cultivated in vitro and were unsuccessful by tests on 10% homogenates of the organs. Horizontal viral transmission of virus by infected hamsters that were viruric was demonstrated in only 1 of 27 normal hamsters that were cocaged for 4 weeks under crowded conditions. General failure to obtain horizontal viral transmission may relate to rapid inactivation of virus in excreted urine. Vertical viral transmission was not demonstrated from five chronically infected female hamsters to their 34 offspring. However, if primary infection occurred during pregnancy, the progeny were either stillborn or died shortly after birth, and thus appeared to represent transplacental viral transmission.
Biological Properties of the Encapsulated
Staphylococcus aureus
M
Authors: Melly M. Ann , Duke Linda J. , Liau Deng-Fong , Hash John H.
Published: January 2020

Strain M, classified as a
Staphylococcus aureus
, behaves like the other rare encapsulated staphylococcal strains. It was clumping-factor negative, grew in diffuse-type colonies in serum-soft agar, and produced rapidly fatal disease in mice. Strain M was highly resistant to phagocytosis by human or mouse leukocytes and required both specific antibody and heat-labile serum factor(s) for efficient ingestion by human polymorphonuclear leukocytes. Electron micrographs confirmed the presence of a large capsule. Agglutination studies, active or passive mouse protection experiments, and opsonic studies revealed that strain M represents a new, immunologically distinct strain of encapsulated staphylococcus. Strain M differs from other known encapsulated staphylococci in several other respects: its cellular and colonial morphology is atypical; its LD
50
in the mouse peritoneal model is 100 times less than that of other mouse lethal strains; it is poorly opsonized by normal human serum; and, finally, it possesses an unusually large capsule as seen in electron micrographs.
Influence of the Alternate Complement Pathway on Opsonization of Several Bacterial Species
Authors: Forsgren Arne , Quie Paul G.
Published: January 2020

In normal human serum chelated with magnesium (10 mM) and ethylene glycotetraacetic acid (10 mM) (MgEGTA), the classical pathway of complement activation is blocked; however, the alternate pathway of complement activation is intact.
Diplococcus pneumoniae, Staphylococcus albus, Streptococcus viridans, Streptococcus faecalis
, and
Serratia marcescens
were opsonized in normal human serum containing 10 mM MgEGTA. In contrast,
Staphylococcus aureus
and
Pseudomonas aeruginosa
were poorly opsonized in human serum chelated with 10 mM MgEDTA. Therefore certain bacterial species appear to require the classical pathway of complement activation to be opsonized and other bacterial species utilize the alternate pathway of complement activation.
Bactericidal Activity of Blood of Rabbits Vaccinated With Homologous Antigens of
Campylobacter fetus
(
Vibrio fetus
)
Authors: Border Maryon , Myers L. L. , Firehammer B. D.
Published: January 2020

Rabbits were vaccinated with the following
Campylobacter fetus
var.
venerealis
(
Vibrio fetus
) antigens: whole-cell (WC), autoclaved (A), boiled (B), and purified postgrowth broth (PGB). Bactericidal activity of freshly drawn heparinized blood against the organism was determined after each vaccination. In all cases bactericidal activity of the blood of vaccinated rabbits was higher than for nonvaccinated rabbits. The in vitro bactericidal activity of the blood was determined in two separate experiments. In experiment I the bactericidal activity of the blood of rabbits vaccinated with PGB antigen was the same as that of rabbits vaccinated with WC antigen and higher than that of rabbits vaccinated with A antigen after the third vaccination. In experiment II the bactericidal activity of blood of rabbits vaccinated with PGB antigen was the same as that of those vaccinated with WC antigen after the second and third vaccinations and higher than for rabbits vaccinated with A antigen after the third vaccination. Blood of rabbits vaccinated with A antigen was less bactericidal than blood of rabbits vaccinated with B antigen after the third vaccination, indicating the presence of a surface antigen destroyed by autoclaving but not by boiling. The in vivo and in vitro whole blood bactericidal tests are more sensitive for measuring the response of rabbits vaccinated with WC, B, A, or PGB antigens than is the plate agglutination test.
Effects of Antigen-Antibody Complexes on the Primary Immune Response in Rhesus Monkeys
Authors: Houston W. E. , Pedersen C. E. , Cole F. E. , Spertzel R. O.
Published: January 2020

A model for the enhancement of the primary humoral immune response of rhesus monkeys to marginal or weakly antigenic vaccines is presented. Our procedure used the complexing of formalin-inactivated Venezuelan equine encephalomyelitis (VEE) virus vaccine with specific, homologous, immune gamma globulin (IgG) at equivalence. Equivalence was determined by combining the concentrated, isotopically labeled (
3
H) virus with various concentrations of specific Sephadex-fractionated IgG. Enhancement of VEE virus antibody response in monkeys was obtained from preparations containing a marginal concentration of antigen that was complexed at equivalence with homologous IgG as compared with antigen alone. Protection in Swiss mice closely paralleled the antibody response pattern observed in monkeys, since complexes at equivalence provided 30 to 50% greater protection against challenge than antigen alone.
Virulence and the Role of Iron in
Pseudomonas aeruginosa
Infection
Authors: Bullen J. J. , Ward C. G. , Wallis S. N.
Published: January 2020

The virulence of
Pseudomonas aeruginosa
can be enhanced by passage in mice or rabbits. Enhanced virulence has some specificity for the host in which the passage is done. Experimental infection in the peritoneal cavity of cannulated rabbits has shown that the injection of iron compounds can lead to a rapid and fatal growth of an otherwise nonlethal dose of bacteria. In vitro the unsaturated iron-binding proteins present in the peritoneal fluid can halve the growth rate of
P. aeruginosa.
The restricted rate of growth is restored to normal if the iron-binding proteins are saturated with iron. Exactly the same results are achieved with purified transferrin. Both fatal and nonfatal infections with
P. aeruginosa
cause a sharp fall in the percentage of saturation with Fe of the plasma and peritoneal fluid. In both normal and infected animals the peritoneal fluid is invariably less saturated than the plasma. Specific antiserum not only protects against death but also against the fall in iron saturation of the plasma and peritoneal fluid. In both fatal and nonfatal infections a high proportion of viable bacteria are unphagocytized in the peritoneal cavity.
Studies on the Mechanism of Endogenous Pyrogen Production II. Role of Cell Products in the Regulation of Pyrogen Release from Blood Leukocytes
Authors: Bodel Phyllis
Published: January 2020

Some characteristics of the process by which endogenous pyrogen (EP), the mediator of fever, is released from cells were examined by using human blood leukocytes incubated in vitro. Studies were designed to examine a possible role for leukocyte products, including EP, in the induction, augmentation, or suppression of pyrogen release by blood leukocytes. Products of stimulated leukocytes, including a partially purified preparation of EP, did not induce significant activation of nonstimulated cells. Also, no evidence was obtained that stimulated cell products either augment or inhibit pyrogen production by other stimulated cells. A feedback control of EP production was thus not observed. A crude preparation of EP, containing other products of activated cells, maintained its pyrogenicity when incubated at pH 7.4 but not at pH 5.0. These studies thus provide no support for hypothesized control mechanisms regulating production of EP by blood leukocytes. By contrast, local inactivation of EP at inflammatory sites may modify the amount of EP entering the blood, and hence fever.
Differentiation of Four Adenovirus Types by Macrophage Migration Inhibition Tests
Authors: Novotny James F. , Hetrick Frank M. , Via David
Published: January 2020

The macrophage migration inhibition (MMI) test was found to be a satisfactory procedure for distinguishing between adenovirus types 1, 4, 5, and 7. Highly purified virus preparations were used for the sensitization of Hartley strain guinea pigs, whereas the MMI test antigen consisted of crude virus preparations grown in KB cells. With all four virus types, a significantly greater MMI response was noted when peritoneal exudate cells were exposed to the homologous sensitizing antigen as compared to that obtained with the three heterologous antigens. Studies with adenovirus type 1 indicate that sensitizing doses between 70 and 150 μg of viral protein per guinea pig gave the optimal MMI response. Doses below 70 μg did not stimulate the delayed response, whereas doses above 120 μg produced MMI reactions which were nonspecific, as differences between homologous and heterologous antigens were not demonstrable.
Growth Inhibition Among Strains of
Neisseria gonorrhoeae
due to Production of Inhibitory Free Fatty Acids and Lysophosphatidylethanolamine: Absence of Bacteriocins
Authors: Walstad Diana L. , Reitz Ronald C. , Sparling P. Frederick
Published: January 2020

Each of 50 tested strains of
Neisseria gonorrhoeae
produced growth-inhibitory substances that were active against most strains of gonococci or meningococci, but not against species other than the
Neisseria.
There were quantitative differences among different strains in production of the inhibitor and sensitivity to it, but not of sufficient magnitude to permit routine strain typing. The inhibitor was associated with the cell pellet (crude cell envelope) and was not inducible with mitomycin C. Inhibitory activity was thermostable and resisted alkali and proteolytic enzymes. The inhibitor was quantitatively recovered from whole cells by chloroform-methanol extraction. Separation of total gonococcal lipids by silica gel chromatography revealed inhibitory activity in both the free fatty acid and the phospholipid fractions. The major phospholipid, phosphatidylethanolamine, had no inhibitory activity, but monoacyl phosphatidylethanolamine, a minor phospholipid, was quite inhibitory. It is likely that the “bacteriocin” of
N. gonorrhoeae
strains results from the degradation of phosphatidylethanolamine to inhibitory long-chain free fatty acids and monoacyl phosphatidylethanolamine.
Serological Reactions of
Mycoplasma hominis
: Differences Among Mycoplasmacidal, Metabolic Inhibition, and Growth Agglutination Tests
Authors: Lin Juey-Shin , Kass Edward H.
Published: January 2020

Seven strains of
Mycoplasma hominis
from human genital tracts were selected to produce antisera. The complement-dependent mycoplasmacidal (MC) activity and two complement-independent activities, metabolic inhibition (MI) and agglutination during growth (GA), of these sera were compared. The GA and MI tests were equivalent in titer and generally not affected by concentration of antigen; they revealed specific cross-reacting patterns among the seven strains. There was little if any cross-reactivity with antisera to other human mycoplasmas or to
Mycoplasma arthritidis.
Control sera from unimmunized rabbits and sera against concentrated uninoculated culture media were also nonreactive. On the other hand, the sensitivity and specificity of the MC test were affected by the concentration of antigen: at about 10
2
color-changing units (CCU) of antigen, all strains were equivalently cross-reactive against the seven antisera, but at 10
2
to 10
4
CCU the individual strain specificity appeared, whereas at about 10
5
CCU little or no antibody was detectable by MC. The MC tests with the lowest concentrations of antigen gave the highest titers of antibody, but at such low concentrations of antigen there was not only loss of individual strain specificity but also some cross-reactivity against other human mycoplasmas,
M. arthritidis
, or control rabbit sera. Studies with paired human sera also indicate that the MC test with small amounts of antigen is more sensitive than GA-MI.
Inhibition of
Pseudomonas aeruginosa
by Hyperbaric Oxygen: Interaction with Mouse Peritoneal Exudate Cells
Authors: Weislow Owen S. , Pakman Leonard M.
Published: January 2020

High-pressure oxygen (HPO) therapy for
Pseudomonas aeruginosa
infections of burn wounds has not been as effective as in vitro studies predicted. Mitigation of HPO toxicity for
P. aeruginosa
by nutrients present at the burn site could explain the lack of in vivo success. Alternatively, HPO-induced depression of host defense mechanisms could negate beneficial effects arising from HPOs known toxicity for
P. aeruginosa.
Accordingly, mouse peritoneal exudate cells (PEC), preincubated for 24 h in 1 atm of air-CO
2
, were used to study the in vitro effects of HPO or air-CO
2
on phagocytosis of
P. aeruginosa
or sheep erythrocytes (SRBC). Subsequent 2-h exposures of PEC to increasing numbers of bacteria, in an air-CO
2
atmosphere, decreased the percentage of bacteria cleared as well as PEC viability. Similar exposures of PEC to bacteria in an HPO atmosphere prevented the loss of PEC viability and increased bacterial clearance. In control experiments, increasing the number of SRBC relative to PEC decreased the percentage of SRBC cleared without decreasing PEC viability, as determined under air-CO
2
; short (2 h) exposure to HPO did not affect SRBC clearance. Microscopic examination of PEC indicated that a 24-h preincubation in HPO decreased the percentage of PEC which could ingest SRBC during subsequent experimental exposures (2 h) to air-CO
2
or HPO. These data suggest that short periods of exposure to HPO promote the ability of PEC to clear pseudomonads by adversely affecting the bacteria. This in turn prevents a pseudomonad-induced depression of PEC viability and function. In contrast, prolonged HPO exposure may be detrimental to phagocytic activity.
Protein Fraction with Immunogenic Potential and Low Toxicity Isolated from the Cell Wall of
Neisseria meningitidis
Group B
Authors: Hill James C. , Weiss Emilio
Published: January 2020

Several fractions were extracted from the cell envelope (CE) of
Neisseria meningitidis
group B and characterized with regard to their morphology, antigenicity, protein composition, and toxicity. Whole bacterial cells were suspended in a medium of low ionic strength and disrupted in a French pressure cell. The crude CE thus obtained were separated into cell membrane (CM) enriched and cell wall (CW) enriched fractions on sucrose density gradients. In addition, CM and CW fractions were separated from CE on the basis of differential solubility in the nonionic detergent, Triton X-100. The Triton-insoluble fraction, containing primarily CW components, was further treated with a mixture of Triton and ethylenediaminetetraacetic acid, which was shown to remove additional protein and most of the lipopolysaccharide. Electron microscope examination of the various fractions revealed typical unit membrane structures in the case of CM, or large, open segments in the case of CW. The Triton-insoluble and especially the Triton-ethylenediaminetetraacetic acid-insoluble fractions consisted of small vesicular structures. All fractions, except the Triton-soluble fraction, when assayed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, were shown to contain one major protein component accounting for more than 50% of the total. Sera from rabbits immunized with the various fractions formed precipitin lines in immunodiffusion tests against the homologous and some of the heterologous fractions. High-titer bactericidal antibodies were also demonstrated in these sera when tested against the homologous strains. Toxicity studies in rats sensitized with lead acetate indicate that the level of contamination of Triton-insoluble/Triton-ethylenediaminetetraacetic acid-insoluble fractions with lipopolysaccharide was significantly smaller than that of the other fractions.
Inhibition by Lysozyme of Growth of the Spherule Phase of
Coccidioides immitis
In Vitro
Authors: Collins Michael S. , Pappagianis Demosthenes
Published: January 2020

Development of mature endosporulating spherules from an endospore inoculum was markedly inhibited by human or hen egg-white (HEW) lysozyme at 5 μg/ml. Mature spherules formed in medium containing 5 μg per lysozyme per ml (3.3 × 10
−7
M) were approximately 50% smaller than control spherules. In addition, lysozyme induced a large portion of the endospore inoculum to revert to the mycelial growth phase. Increasing lysozyme concentrations to 10 or 20 μg/ml prompted a nearly complete reversion of the inoculum to the mycelial phase. Mature endosporulating spherules removed from growth medium and resuspended in a solution of human or HEW lysozyme at 18 μg/ml in distilled water prompted leakage of four to five times as much of materials absorbing maximally at 260 nm into the supernatant as untreated control spherules during 90 min of incubation. This four- to fivefold increase in nucleotide loss was evident at 4, 25, and 37 C. The permeability of 1-day-old immature spherules and 8-day-old endospores was considerably altered by lysozyme treatment of cells suspended in distilled water. Large amounts of potassium and nucleotides were rapidly lost by each type of cell when treated with 20 μg of lysozyme per ml. After 270 min of exposure to lysozyme, 98% of the immature spherules and 25% of the endospores were nonviable. Lysozyme adsorption by formalin-killed spherules in the presence of varying concentrations of calcium ion and the rapid alteration of permeability seen after lysozyme treatment suggested that the cell membrane was damaged as a result of binding lysozyme.
Intraperitoneal Mouse Virulence of
Salmonella typhimurium
Hybrids Expressing Somatic Antigen 9
Authors: Johnson E. M. , Snellings Norma J. , Life Charles A. , Baron L. S.
Published: January 2020

Salmonella typhimurium
hybrids expressing somatic antigen 9 after mating with either
S. typhosa
or
S. enteritidis
Hfr donors did not differ from their
S. typhimurium
parent with respect to the number of organisms required to produce death in mice inoculated intraperitoneally.
Soluble Antigens of Mycelia and Spherules in the In Vitro Detection of Immunity to
Coccidioides immitis
Authors: Deresinski Stanley C. , Levine H. B. , Stevens David A.
Published: January 2020

The effect of a
Coccidioides immitis
spherule-derived antigen (spherulin) upon in vitro thymidine uptake by sensitized and nonsensitized lymphocytes was studied, and optimal conditions for the assay were determined. The mitogenic portion of the antigen was shown to be nondialyzable, as was true for a mycelial-derived antigen (coccidioidin). Concentrations of 20 μg of nondialyzable spherulin solids and 17 μg of nondialyzable coccidioidin solids per ml of culture were shown to be suitable for differentiating skin test-positive from skin test-negative individuals. Comparison with mycelial filtrate suggested spherulin may be a more potent mitogen for sensitized lymphocytes.
Passive Transfer of Delayed Hypersensitivity to
Blastomyces dermatitidis
Between Mice
Authors: Scillian James J. , Cozad George C. , Spencer Harry D.
Published: January 2020

This study further characterized the delayed hypersensitivity state induced in animals by
Blastomyces dermatitidis
exposure. Passive transfer of delayed hypersensitivity by transfer of cells and inhibition of migration of peritoneal exudate cells were studied, using sensitized mice of two inbred strains. Donor mice were subcutaneously inoculated with viable
B. dermatitidis
yeast cells. After 15 days, spleen cells or serum from these animals were injected intravenously into normal recipients of the same strain. After 24 h these mice were footpad tested with killed
B. dermatitidis
yeast cell antigen. Mice receiving spleen cells from sensitized animals had a significant increase in footpad thickness 24 to 48 h after testing. Those receiving only serum remained negative. Migration of peritoneal exudate cells from blastomyces-sensitive donor mice was inhibited by presence of blastomycin but not by mycobacterial antigen. Neither blastomyces-sensitive nor control animals reacted to footpad or migration inhibition testing with mycobacterial antigen.
Synergistic Action of Cord Factor and Mycobacterial Sulfatides on Mitochondria
Authors: Kato Masahiko , Goren Mayer B.
Published: January 2020

The mechanism of a synergistic toxicity of 6,6′-dimycoloyl-α,α′-
d
-trehalose (cord factor) and 2,3,6,6′-tetraacyl-α,α′-
d
-trehalose 2′-sulfate (sulfolipid I) for mice was studied. Sulfolipid I was entirely nontoxic, but it markedly accelerated the lethal toxicity of cord factor for mice. In vivo, sulfolipid I affected neither respiration nor accompanying phosphorylation of mouse liver mitochondria, whereas in vitro, it induced a swelling and disruption of mitochondrial membranes and strongly inhibited mitochondrial oxidative phosphorylation. The effect of sulfolipid I on mitochondrial structure and function in vitro was neutralized by bovine serum albumin and various animal sera, whereas that of cord factor and cord factor plus sulfolipid I was not prevented by bovine serum albumin. The simultaneous injection of cord factor and sulfolipid I caused an intensive fragmentation of mitochondria and a marked decrease in respiratory and phosphorylative activity in mitochondria. These data indicate that sulfolipid I can achieve an effective attack on mitochondria in combination with cord factor in vivo and induces heavier damage in mitochondrial structure and function than that produced by cord factor alone.
Cell-Mediated Immunity in Humans During Viral Infection: Dermal Hypersensitivity and In Vitro Lymphocyte Proliferation During Mild Viral Respiratory Infections
Authors: Kauffman Carol A. , Linnemann Calvin C. , Tan James S. , Schiff Gilbert M. , Phair John P.
Published: January 2020

In vitro lymphocyte proliferation in response to phytohemagglutinin and streptokinase-streptodornase and delayed dermal hypersensitivity to several antigens were assessed in patients with mild viral upper respiratory infections. The response to phytohemagglutinin in 18 patients was not diminished during the viral infection. Deoxyribonucleic acid synthesis induced by streptokinase-streptodornase remained unaffected by the viral illness in five patients, and skin test reactivity was not depressed during the viral infection. Thus, it appeared that localized viral upper respiratory infections were not associated with suppression of systemic cell-mediated immunity.
Mechanism of the Heparin Effect on the Nitroblue-Tetrazolium Slide Test
Authors: Hohn David C. , Lehrer Robert I.
Published: January 2020

The nitroblue-tetrazolium (NBT) slide test has been applied widely to assist in the diagnosis of bacterial infection. The test involves mixing a small amount of heparinized blood with a solution of NBT and noting the percentage of neutrophils that contain reduced NBT after a fixed period of incubation. Although it has been recognized that anticoagulants can influence the scores obtained, the mechanism of this effect has not been widely appreciated. We have observed that particles are formed when NBT and heparin are mixed, and that these particles are ingested by human neutrophils. Major changes in human neutrophil metabolism result from minor changes in the relative concentrations of heparin and NBT. These observations may explain many discrepancies that have been reported on the NBT slide test by various investigators.
Interferon Induction by Poly(I):Poly(C) Enclosed in Phospholipid Particles
Authors: Straub Stephan X. , Garry Robert F. , Magee Wayne E.
Published: January 2020

Liposomes were prepared with phospholipids (sphingomyelin, lecithin, and phosphatidylethanolamine) in combination with cholesterol and charged lipids (dicetyl phosphate and stearylamine) and contained either poly(I):poly(C) or poly(I). Neutral and positively charged liposomes attached much better to L-929 cells in tissue culture than did negatively charged particles. Liposomes were toxic to L cells at relatively low concentrations, making the determination of antiviral activity induced by particles containing poly(I):poly(C) difficult to measure by the plaque reduction assay. When injected into mice, all of the liposomes containing poly(I):poly(C), except phosphatidylethanolamine liposomes, greatly potentiated and extended the serum interferon response of poly(I):poly(C). Lecithin and sphingomyelin liposomes given intravenously were ten times more effective than free poly(I):poly(C) in stimulating production of serum interferon. Sphingomyelin liposomes containing [
14
C]poly(I):poly(C) were 88% cleared from the bloodstream of mice by 3 min after intravenous injection. Most of the radioactivity (70%) was captured by the liver and remained there for at least 4 h. By 2 h, 7% of the radioactivity could be found in the spleen. Five percent of the radioactivity was found in the lungs at 30 min, with decreasing amounts thereafter. Small amounts of radioactivity were found in the muscle and kidneys. The spleen was shown to contain appreciable levels of interferon at 4 h, and low levels were found in the liver. Radioactivity accumulated slowly in the liver following an intraperitoneal injection of sphingomyelin liposomes containing [
14
C]poly(I):poly(C). By 4 h, 26% of the dose was recovered from the liver and 4.9% from the spleen, with small amounts in the lung, kidney, and omentum.
Growth of Typhoid and Paratyphoid Bacilli in Intravenously Infected Mice
Authors: Carter Philip B. , Collins Frank M.
Published: January 2020

The in vivo growth of
Salmonella paratyphi
A,
S. paratyphi
B,
S. paratyphi
C, and
S. typhi
, as well as of an
S. typhi-typhimurium
hybrid, was studied in three different strains of mice.
S. paratyphi
A and B and
S. typhi
demonstrated very little growth potential in any of the intravenously infected mice, even after as many as 20 serial mouse passages. It was noted, however, that small numbers of viable
S. paratyphi
B and
S. typhi
persisted in the spleens of infected mice for up to 28 days.
Salmonella paratyphi
C and the
S. typhi-typhimurium
hybrid gave rise to progressive systemic infections beginning from very small intravenous inocula. The median lethal doses for the C57B1 strain of mouse were about five organisms. The relevance of these findings with regard to the development of an animal model for studying human typhoid fever vaccines is discussed.
Disaggregation of Endotoxin by Isolated Rat Liver Plasma Membranes and Lack of Product Binding
Authors: Jones Robert B. , Staton Annie J. , Kiesow Lutz A.
Published: January 2020

The interaction of bacterial endotoxin with isolated rat liver cell membranes was studied to determine the extent and nature of any binding.
Serratia marcescens
endotoxin was incubated with isolated rat liver plasma membranes for varying periods of time at 37 C, and this mixture was then centrifuged through a discontinous sucrose density gradient. The membranes banded primarily at the 35 to 45% sucrose interface, whether or not they had been incubated with endotoxin. The endotoxin distributed itself throughout the gradient except when incubated with membranes, in which case it failed to sediment. This membrane-induced alteration in sedimentation could be prevented by heat inactivation of the membranes, and was found to be pH, time, temperature, and concentration dependent. There was neither associated degradation of the endotoxin, as measured by molecular sieve chromatography, nor loss in toxicity, as determined in lead-sensitized rats. These observations are consistent with an enzymatic disaggregation of the endotoxin by membranes and could represent a step in the uptake of the endotoxin by the reticuloendothelial system. No significant binding of this disaggregated endotoxin to the membranes could be detected, either after gradient separation or after repeated washing. This finding strongly suggests that, at least in cells that are active in the uptake of endotoxin, membrane-endotoxin interactions may be relatively transitory in nature, and that firm adherence to such membranes may not be a central feature of endotoxin toxicity.
Proposed Reproductive Cycle for a Relatively Stable L-Phase Variant of
Streptococcus faecalis
Authors: Green Mary T. , Heidger Paul M. , Domingue Gerald
Published: January 2020

Based on electron microscopic observations, the reproductive cycle of a relatively stable L-phase variant of
Streptococcus faecalis
was proposed. The small, dense, nonvesiculated L-form is envisioned as the central (core) element. It was seen to divide and bud rapidly. In addition, the dense forms appeared to be capable of growth and development within vesicles of mature mother forms. When these forms were released from the vesicles into the surrounding fluid medium, further growth occurred, resulting in the development of immature and ultimately mature mother forms. Under conditions unfavorable for L-form growth, these dense forms developed first into transitional forms and then into the bacterial form. These dense forms might therefore be considered as undifferentiated “stem cells' with the capacity to develop along several different routes, depending upon the stimulus received.
Immunological Studies of Anergic Patients
Authors: Van Epps Dennis E. , Frierson J. Alan , Williams Ralph C.
Published: January 2020

Sixty-one patients with a variety of different illnesses were studied with respect to skin test anergy and the presence of serum chemotactic inhibitors. In initial testing, 55% of the patient tests demonstrated negative skin test responses to all six test antigens. Sera from 65% of these anergic patients were capable of suppressing the migration of normal polymorphonuclear leukocytes toward chemotactic factors. Statistical analysis of the association of anergy and chemotactic inhibitory sera resulted in a
P
value of <0.0005. Chemotactic inhibitory sera were also capable of suppressing monocyte chemotaxis. No association of chemotactic inhibitory activity and lymphocytotoxic antibody or suppressors of mitogen-induced lymphocyte blast transformation were noted. In addition, T-cell populations in some anergic patients were studied by the erythrocyte-binding technique. Erythrocyte-binding lymphocytes in anergic patients were significantly suppressed when compared to normal controls, but not when compared to skin test-positive patients. The data presented here indicate a close parallel between skin test anergy and the presence of serum chemotactic inhibitory activity. The exact relationship is yet undefined but may indicate the involvement of chemotactic inhibitors as immunological regulators in the host during a variety of systemic illnesses.
Polymyxin B-Induced Release of Low-Molecular-Weight, Heat-Labile Enterotoxin from
Escherichia coli
Authors: Evans Doyle J. , Evans Dolores G. , Gorbach Sherwood L.
Published: January 2020

Polymyxin B-induced release of enterotoxin from
Escherichia coli
strain H-10407 was demonstrated. Incubation of
E. coli
cells derived from 6-h cultures with polymyxin caused the rapid release of enterotoxin with a molecular weight of approximately 20,000, as estimated by the gel filtration technique. The rapidity of the release of enterotoxin indicates that it probably resides in the periplasmic space of the cell. The low-molecular-weight enterotoxin possessed vascular permeability factor and diarrheagenic activities, both of which were found to be heat-labile. The permeability factor activity of this enterotoxin was neutralized by antisera prepared against crude
E. coli
enterotoxin,
Vibrio cholerae
enterotoxin (choleragen), and
V. cholerae
toxoid (choleragenoid), respectively. Supernatant fluids of 6-h
E. coli
cultures did not contain this molecular form of enterotoxin but did contain very high-molecular-weight, heat-labile enterotoxin. Incubation of cells derived from older (18 h) cultures with polymyxin caused the release of both low- (20,000) and high-molecular-weight forms of enterotoxin. We concluded that either the 20,000-dalton form of heat-labile enterotoxin is not released by
E. coli
under in vitro growth conditions or that enterotoxin released in this form is rapidly destroyed or inactivated.
Development and Passive Transfer of Immunity to Gonococcal Infection in Guinea Pigs
Authors: Scales R. W. , Kraus S. J.
Published: January 2020

Gonococcal infections of relatively long duration were produced in guinea pigs with minimal infective doses ranging from 10
1
to 10
2
colony-forming units. After spontaneous eradication and upon rechallenge with ≥10
8
gonococcal colony-forming units, guinea pigs were refractory to infection. Serum from these guinea pigs was bactericidal in vitro and protected virgin guinea pigs from in vivo challenge. The 7
S
peak, but not the 19
S
peak, from gel filtered immune serum demonstrated both bactericidal and passive protective properties. In vitro bactericidal activity of whole immune serum and its 7
S
peak was abolished after heating at 56 C for 30 min. The in vivo protective ability of the 7
S
peak was not abolished after heating.
Immunotherapy of Cancer with Nonliving BCG and Fractions Derived from Mycobacteria: Role of Cord Factor (Trehalose-6, 6′-Dimycolate) in Tumor Regression
Authors: Bekierkunst A. , Wang L. , Toubiana R. , Lederer E.
Published: January 2020

Delipidated and deproteinized cell walls from
Mycobacterium tuberculosis
H37Ra suspended in 1.25% mineral oil emulsion cured established tumors in the skin and metastases in draining lymph nodes of guinea pigs (strain 2) after intratumoral administration in 33% of the cases examined. This was increased to 83% when a mixture of cord factor and the delipidated cell walls was used. A similarly high percentage of cures was obtained after administration of lyophilized, killed BCG alone or with addition of cord factor in 1% mineral oil emulsion. Lyophilized, killed BCG dispersed in a solution of tocopherol acetate in peanut oil or in peanut oil alone showed a limited tumor-regressive activity (36%). However, a mixture of BCG and cord factor suspended in the above media cured 80 and 69% of the treated animals, respectively.
Differential Production of Interferon and Refractoriness Inducing Principle in L Cells
Authors: Chadha Kailash C. , Davey Mary W. , Byrd Daniel M. , Carter William A.
Published: January 2020

The extracellular, acid-soluble cell products (EASCP) from Newcastle disease virus-infected L
929
cells contain both interferon, defined as antiviral activity, and refractoriness inducing principle, defined as an activity that inhibits interferon production. L cells pretreated with EASCP and then infected with Newcastle disease virus give rise to EASCP with decreased amounts of interferon but an increased ratio of refractoriness inducing principle activity to interferon activity in a dose related manner. The antiviral activity of an EASCP preparation is not dependent upon its refractoriness inducing principle level, but is entirely dependent on its interferon content. Our results provide additional evidence that interferon and refractoriness inducing principle are different biological entities and not polymorphic functions of the interferon molecule.
Bovine Venereal Vibriosis: Variations in Immunoglobulin Class of Antibodies in Genital Secretions and Serum
Authors: Corbeil L. B. , Duncan J. R. , Schurig G. G. D. , Hall C. E. , Winter A. J.
Published: January 2020

The immunoglobulin classes of antibodies to
Campylobacter (Vibrio) fetus
in cervicovaginal mucus (CVM) were determined by the indirect fluorescent antibody test at sequential periods, since the order of class appearance has not been established for specific secretory immune responses. In the local immune response to
C. fetus
immunoglobulin M (IgM) antibodies appeared first, immunoglobulin A (IgA) antibodies next, and immunoglobulin G (IgG) last. IgM antibodies were quite transient, but IgG antibodies remained longer, and those of the IgA class persisted until the end of the experimental period (up to 10 months). Since differences appear to exist between immune mechanisms at cervicovaginal and uterine sites, as well as between immune responses induced by local and systemic immunizations, the immunoglobulin classes of antibodies in uterine secretions were compared with the classes in CVM and serum. Uterine antibodies arose coincidently with uterine lesions in heifers slaughtered after short periods of infection. In convalescent animals only IgA antibodies were found in CVM, whereas the predominant class of antibodies in the uterine secretions was IgG
1
in three of four animals studied. Only IgG antibodies were detected in CVM and uterine secretions of systemically immunized animals. These findings could account for faster clearance of
C. fetus
from the uterus than from the cervicovaginal area in locally infected animals and for failure of colonization in systemically immunized animals, because IgG antibodies are good opsonins and IgA antibodies are not. IgA antibodies do immobilize
C. fetus
, however, so they could prevent recolonization of the uterus in cervicovaginal carriers.
Immunogenicity of Ribosomal Preparations from Yeast Cells of
Histoplasma capsulatum
Authors: Feit Carl , Tewari Ram P.
Published: January 2020

Protective immunity was elicited by immunization of mice with ribosomal preparations from yeast cells of
Histoplasma capsulatum
. Ribosomes from disrupted cells were isolated by differential centrifugation using sodium dodecyl sulfate. These preparations contained 55% protein and 45% ribonucleic acid and sedimented as a single peak with a sedimentation coefficient of 77
S
on sucrose density gradient analysis. Mice immunized subcutaneously with ribosomes, with or without adjuvant, were challenged intravenously with 8 × 10
6
yeast cells of
H. capsulatum
. Significant protection was induced by ribosomes and was greatly enhanced by adjuvants. Protection measured by 30-day survival compared favorably with the immunoprotection assessed by absence of lung lesions and negative spleen cultures. Treatment of ribosomes with ribonuclease before immunization reduced protection by 85%, whereas trypsin and Pronase reduced the protection by 50 to 55%. These findings indicate that both intact ribosomal ribonucleic acid and protein are necessary for maximal immunogenicity of
Histoplasma
ribosomes.
Effects of Dextran Sulfate 500 on Cell-Mediated Resistance to Infection with
Listeria monocytogenes
in Mice
Authors: Hahn H.
Published: January 2020

Injection of dextran sulfate 500 caused loss of antibacterial resistance. Mice became more susceptible to an infection with
Listeria monocytogenes
and were unable to develop antilisterial immunity after both active and passive immunization with passively administered spleen cells from
Listeria
-immune donors. Indirect evidence suggests that the phagocytic component of cell-mediated resistance to bacterial infection is the site of attack of dextran sulfate.
Morphological Changes Induced by Dextran Sulfate 500 in Mononuclear Phagocytes of
Listeria
-Infected Mice
Authors: Hahn Helmut , Bierther Manfred
Published: January 2020

Morphological changes involving mononuclear phagocytes in
Listeria
-infected mice after treatment with dextran sulfate 500 were investigated. Mononuclear phagocytes in livers and spleens, both circulating monocytes and fixed macrophages, showed uptake of electron-dense material. Mononuclear phagocyte changes were most pronounced within granulomatous lesions, where many phagocytes showed large membrane-bound inclusions and extensive cellular damage. It is concluded that dextran sulfate 500 selectively damages mononuclear phagocytes and that, in listerial infection, dextran sulfate 500 renders mononuclear phagocytes unable to express cellular resistance.
Ultrastructure of Mutants of
Streptococcus mutans
with Reference to Agglutination, Adhesion, and Extracellular Polysaccharide
Authors: Nalbandian J. , Freedman M. L. , Tanzer J. M. , Lovelace S. M.
Published: January 2020

An electron microscopic study of
S. mutans
6715-13 wild type and representatives of three distinct classes of glucan synthesis-defective mutants (which fail to form adherent microbial plaques but agglutinate normally in the presence of exogenous glucans) disclosed the presence of two sucrose-dependent, glucanase-sensitive, extracellular components. In the wild type, these extracellular glucans had predominantly fibrillar (with some globular) morphologies. However, in the mutant strains, there was a consistent reduction in or loss of the fibrillar components and dramatic increases in globular forms. A cell surface-associated fuzzy coat was consistently seen, and it was neither sucrose-dependent nor glucanase-sensitive. The data indicated that in vitro and in vivo adhesion and virulence at smooth tooth surfaces (all these properties dramatically reduced in the mutants) were causally and functionally related to the extracellular, fibrillar, glucan component, whereas in vitro glucan-mediated agglutination may be related to the cell-associated surface fuzzy coat.
Reactions of β-Lysin with Purified Cytoplasmic Membranes of
Bacillus megaterium
Authors: Gooch Gary T. , Donaldson David M.
Published: January 2020

The bactericidal activity of β-lysin was inactivated when it reacted with purified protoplasmic membranes. This reaction caused the membranes to fragment and lose their unit structure.
Influence of Androgen and Estrogen on Delayed Skin Test Reactivity to
Candida albicans
Authors: Rifkind David , Frey Janet A.
Published: January 2020

Recipient adult male CFW mice were passively sensitized to candida delayed skin test reactivity with splenic lymphoid cells from candida-vaccinated donor females. In recipient adult males that had been bilaterally gonadectomized as weanlings, before passive sensitization, reactivity was less than in the unilaterally gonadectomized controls. Adult males bilaterally gonadectomized as weanlings were treated with gonadal hormones during passive sensitization. 17β-estradiol was found to decrease reactivity, whereas testosterone was found to increase reactivity. These data provide evidence that delayed skin test reactivity produced by female lymphoid cells is depressed by estrogen and is stimulated by androgen.
Cigarette Smoking, Air Pollution, and Immunity: a Model System
Authors: Nulsen A. , Holt P. G. , Keast D.
Published: January 2020

BALB/c mice were exposed to fresh cigarette smoke, a mixture of SO
2
(5 ppm) and CO (50 ppm), or both for periods up to 18 weeks. After varying exposure times, animals were intratracheally inoculated with 10
8
sheep erythrocytes and sacrificed 7 days later, during which time the various exposure regimes were continued. Plaque-forming-cell responses were measured in spleens and a pool of the cervical and mediastinal lymph nodes, together with serum hemagglutinating and hemolytic responses, and compared with those of age-matched control animals. Both the organ and serum responses exhibited stimulation in the early phase of exposure, before a depression with prolonged exposure. The greatest depression was seen in animals that had been chronically exposed to both fresh cigarette smoke and the gas mixture.
Intracellular and Extracellular Degranulation of Human Polymorphonuclear Azurophil and Specific Granules Induced by Immune Complexes
Authors: Leffell Mary S. , Spitznagel John K.
Published: January 2020

The nature of the phagocytic stimulus determines the degree of degranulation. Specifically, immune complexes induced more degranulation than did antigen or antibody alone. The release of constituents from the two granule classes represented independent phenomena. Relatively more of the specific granule proteins were released into the medium during phagocytosis, whereas more of the azurophil proteins were associated with the phagosomes.
Immunological Analysis of Glycolipids and Lipopolysaccharides Derived from Various Mycoplasmas
Authors: Sugiyama T. , Smith P. F. , Langworthy T. A. , Mayberry W. R.
Published: January 2020

The lipids and lipopolysaccharides of five mycoplasmas were examined for complement-fixing activity to antimembrane rabbit sera. Total glycolipid fractions and the aqueous phenol fractions (lipopolysaccharides) from the membranes of
Acholeplasma laidlawii, A. modicum, A. axanthum
, and
Mycoplasma neurolyticum
exhibited significant antigenic activity. The glycolipids and phosphoglycolipids from
Thermoplasma acidophilum
were either anticomplementary or did not react due to their extreme hydrophobic nature. High activity was found using the lipopolysaccharide of
T. acidophilum
. The pure glycolipids and phosphoglycolipids of the
Acholeplasma
and
Mycoplasma
species also exhibited significant complement-fixing activity. Acylation of the sugar residues of these lipids reduced or negated complement-fixing activity. Double cross-reactions between the glycolipids of
A. laidlawii
and
A. modicum
appeared to be due to mono- and diglucosyl diglycerides of identical structure. Specificity of glycolipid structure was noted by the absence of cross-reactions between
A. laidlawii
and
M. neurolyticum
, the glycolipids of which differ only in the nature of the glucose linkages. The existence of lipopolysaccharides in the membranes of mycoplasmas and their complement-fixing activity in the presence of antimembrane sera suggest their possible importance as specific antigenic determinants.
Degradation of Sucrose by Whole Cells and Plaque of
Actinomyces naeslundii
Authors: Miller Chris H.
Published: January 2020

Whole cells of
Actinomyces naeslundii
ATCC 12104, either in a dispersed form or in the form of plaque, enzymatically degraded sucrose to glucose and fructose. Washed whole cells expressed β-fructofuranosidase specificity and hydrolyzed sucrose to essentially equimolar quantities of glucose and fructose. The cells readily hydrolyzed sucrose, raffinose, and
Actinomyces viscosus
or
Aerobacter levanicum
levan, but did not degrade melezitose, maltose, α-methyl-
d
-glucoside, melibiose, glucose-1-phosphate, or dextran T-500. Sucrose degradation occurred at a temperature optimum of 37 to 45 C and at a pH optimum of 5.7 to 6.0. The

K
m

for sucrose was 0.05 M. Sucrose or raffinose in the growth medium resulted in cells with a specific activity that was fivefold greater than that of cells grown in medium supplemented with either glucose, fructose, maltose, lactose, or glucose and fructose, or grown in unsupplemented medium. Addition of sucrose to log-phase cells growing in glucose also increased the specific activity. Degradation of sucrose by whole cells in the form of plaque also occurred, but 6% less free fructose than free glucose was recovered. Sucrose-dependent synthesis of extracellular levan or glucan by whole cells or plaque could not be demonstrated. The ability of
A. naeslundii
to degrade sucrose and levan may be related to the pathogenic potential of this bacterium in plaque-associated oral diseases.