bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum and intestinal immune response to rotavirus enteritis in children
Authors: Davidson G P , Hogg R J , Kirubakaran C P
Published: January 2020

This study was designed to assess the serum and mucosal immune response to naturally acquired rotavirus enteritis in children. Serum and duodenal secretions were collected 1 week and again 4 to 5 weeks after the onset of illness from 10 children. In two of these children, the procedure was repeated 12 to 15 months later. Another 10 children with bacterial enteritis were studied as controls. The antibody response in serum included a significant elevation of rotavirus-specific immunoglobulin M (IgM) in acute-phase samples (P less than 0.05), but not in convalescent-phase samples, when compared with controls. Rotavirus-specific IgG and IgA levels were significantly elevated in convalescent-phase serum when compared with acute-phase serum (P less than 0.025), but not in control serum. Rotavirus-specific IgA levels in convalescent duodenal secretions were significantly raised when compared with both acute-phase and control samples (P less than 0.01). Rotavirus-specific IgM levels were elevated in acute-phase duodenal secretions (P less than 0.05), but not in convalescent-phase secretions. In two children, the secretory IgA response had disappeared by 12 months. These studies demonstrate the presence of rotavirus-specific antibody in duodenal secretions which may be important for protection against reinfection and may be capable of being stimulated by oral vaccination.
Modification of macrophage phagocytosis in murine cryptococcosis
Authors: Morgan M A , Blackstock R A , Bulmer G S , Hall N K
Published: January 2020

Normal C57BL/6J peritoneal cells exhibited a decreased phagocytosis when cultured with a cell wall antigen of Cryptococcus sp. and lymphocytes from mice infected with C. neoformans. Direct cell-to-cell interaction was not required in that supernatant fluids from cultures of lymphocytes from infected animals could be incubated with normal macrophage monolayers to give comparable suppression. The induction of the suppressor factor required specific cryptococcal antigen; however, suppression at the macrophage level was nonspecific in that the phagocytosis of C. neoformans and Saccharomyces cerevisiae were both decreased. Suppression appeared with lymphocyte supernatants taken from mice infected for 14 days and thereafter. The factor was heat stable, trypsin sensitive, and allospecific.
Effect of immunization with pneumolysin on survival time of mice challenged with Streptococcus pneumoniae
Authors: Paton J C , Lock R A , Hansman D J
Published: January 2020

The role of the cytolytic toxin pneumolysin in the pathogenicity of Streptococcus pneumoniae was investigated. Pneumolysin was purified to homogeneity and used to immunize mice. When these mice were subsequently challenged via the nasal route with virulent S. pneumoniae, they survived significantly longer than control mice. The mean survival times were 5.52 and 2.48 days for immunized and control mice, respectively. This work provides direct evidence for the involvement of pneumolysin in pneumococcal pathogenicity.
Persistence of associated gram-negative bacteria in experimental actinomycotic lesions in mice
Authors: Jordan H V , Kelly D M
Published: January 2020

Mixed actinomycotic infections were established in a susceptible weanling mouse model by using combinations of Actinomyces israelii and Eikenella corrodens or A. israelii and Actinobacillus actinomycetemcomitans. Acute lesions caused by either of the gram-negative organisms alone were resolved within a few weeks; however, these organisms persisted up to 3 months in chronic lesions in combination with A. israelii.
Mouse hepatitis virus type 4 infection of primary glial cultures from genetically susceptible and resistant mice
Authors: Collins A R , Tunison L A , Knobler R L
Published: January 2020

Mouse hepatitis virus type 4 infection of primary glial cultures, which consisted principally of astrocytes (marked by glial fibrillary acidic protein) from encephalitis-susceptible BALB/c or F1 (BALB/c x SJL/J) hybrid mice and resistant SJL/J mice, was studied. Primary neuron cultures from BALB/c and F1 hybrid mice were previously shown to be permissive and were destroyed within 5 days by infection with mouse hepatitis virus type 4, whereas neurons from SJL/J mice were fully resistant. In contrast, in the present study a chronic infection was established and maintained for up to 18 days in glial cultures from all three mouse strains. Infected SJL/J mouse glial cultures produced 10- to 50-fold less infectious virus and showed less cytopathic effect than did cultures from either infected BALB/c or F1 hybrid mice. Cytopathic effect was evident initially in cells from all three strains, and continued virus production occurred in the presence of limited additional cytopathic effect. These results were not due to the production of detectable levels of interferon. This study showed that SJL/J mouse primary glial cultures were permissive for mouse hepatitis virus type 4 infection whereas SJL/J primary neuron cultures were not, and that there was an early lytic phase of infection followed by chronic infection in all three strains.
Arachidonic acid metabolism in polymorphonuclear leukocytes from patients with chronic granulomatous disease
Authors: Smith D M , Walsh C E , Dechatelet L R , Waite M
Published: January 2020

The effect of the calcium ionophore A23187 on the release and metabolism of [3H]arachidonic acid was examined in normal polymorphonuclear leukocytes and those obtained from patients with chronic granulomatous disease. The ionophore A23187 which stimulates oxidative metabolism in normal polymorphonuclear leukocytes was ineffective in increasing oxidative metabolism (chemiluminescence) in polymorphonuclear leukocytes from patients with chronic granulomatous disease. However, the ionophore A23187 stimulated the release of [3H]arachidonic acid from chronic granulomatous disease neutrophil phospholipids and stimulated its metabolism into hydroxyeicosatetraenoic acids and leukotrienes.
Influence of preformed antibody on the pathogenesis of experimental Candida albicans endocarditis
Authors: Scheld W M , Calderone R A , Brodeur J P , Sande M A
Published: January 2020

The influence of preformed antibody on the induction of experimental Candida albicans endocarditis was investigated by both in vitro and in vivo techniques. Preincubation of C. albicans with immune serum (raised in rabbits by intravenous injection of Formalin-killed yeast cells) decreased adhesion to the constituents of nonbacterial thrombotic endocarditis, e.g., fibrin plus platelets, in vitro. Two different methods, with radiolabeled or viable yeast cells, were confirmatory and demonstrated decreased adhesion of immune serum-treated C. albicans cells to 0 to 7.8% of control values (P less than 0.001). These results correlated with protection from the development of C. albicans endocarditis in the immunized rabbits. The mean (+/- standard deviation) infectious dose for 50% of the animals was 10(5.29) +/- 10(0.07) in 48 control animals versus 10(7.11) +/- 10(0.22) in 37 immunized rabbits (P less than 0.001). These studies suggest that humoral antibody may protect against C. albicans endocarditis, perhaps through inhibition of adhesion, a crucial early step in the pathogenesis of endocarditis.
Isolation and characterization of macrophage phagosomes containing infectious and heat-inactivated Chlamydia psittaci: two phagosomes with different intracellular behaviors
Authors: Zeichner S L
Published: January 2020

Infectious Chlamydia psittaci enters macrophages via a cytochalasin B-insensitive pathway in which chlamydia-containing phagosomes do not fuse with lysosomes; heat-inactivated C. psittaci enters macrophages via a route in which phagosomes do fuse with lysosomes. In an attempt to explain these differences, phagosomes containing infectious and heated chlamydiae were isolated from mouse macrophages by a procedure developed to isolate L-cell chlamydial phagosomes by rate zonal centrifugation. Macrophage phagosomes acted similarly to L-cell phagosomes on dextran and discontinuous sucrose gradients and exhibited similar detergent sensitivities. Total proteins of the two phagosomes were compared with each other, L-cell proteins, and surface-labeled proteins from macrophages. Both macrophage phagosome membranes had at least nine proteins with equal sodium dodecyl sulfate-polyacrylamide gel electrophoresis mobilities; some were the same as L-cell phagosome proteins. Each phagosome had at least one protein not seen in the other. Only two phagosome proteins had mobilities equal to macrophage plasma membrane proteins. Macrophage phagosomes containing infectious and heat-inactivated C. psittaci, although created by different entry mechanisms and destined for different intracellular fates, exhibited only a few differences in their proteins.
Splenic requirement for antigenic variation and expression of the variant antigen on the erythrocyte membrane in cloned Plasmodium knowlesi malaria
Authors: Barnwell J W , Howard R J , Coon H G , Miller L H
Published: January 2020

Variant antigens appear on the surface of Plasmodium knowlesi-infected erythrocytes as the asexual parasite matures and are detected by antibody-mediated schizont-infected cell agglutination (SICA). We now show that cloned parasites can undergo antigenic variation in nonsplenectomized monkeys. In addition, we previously described a new P. knowlesi phenotype in which uncloned parasites passaged in splenectomized monkeys were no longer agglutinable by immune sera. We have designated this new phenotype SICA[-] and the one expressing the variant antigen SICA[+]. Cloned parasites can also switch from SICA[+] to SICA[-] in splenectomized monkeys. The switch from SICA[+] to SICA[-] is a gradual process that requires sequential subpassage in several monkeys. After passage in one monkey, the agglutination titer decreased 4- to 16-fold. Decreased agglutination was associated with decreased antibody binding on all infected erythrocytes as measured by fluorescein-conjugated anti-rhesus monkey immunoglobulin. The asexual malaria parasite can therefore alter its expression of variant antigen in response to the host environment (antivariant antibody or splenectomy). When cloned SICA[-] parasites were inoculated into intact monkeys, two courses of parasitemia were observed: fulminant parasitemia (greater than 20%) and parasitemia that was controlled. Fulminant infections were associated with conversion of the parasite from SICA[-] to SICA[+], i.e., from nonexpression to expression of the variant antigen on the erythrocyte surface. Parasitized erythrocytes remained SICA[-] in those infections that were controlled. It appears, therefore, that the expression of the variant antigen on the erythrocyte surface may influence parasite virulence.
Use of mice tolerant to lipopolysaccharide to demonstrate requirement of cooperation between macrophages and lymphocytes to generate lipopolysaccharide-induced colony-stimulating factor in vivo
Authors: Williams Z , Hertogs C F , Pluznik D H
Published: January 2020

Injection of lipopolysaccharide (LPS) into mice was followed by a rapid elevation of colony-stimulating factor (CSF) in the serum. A second, challenging injection of LPS given 3 to 4 days later failed to induce elevated levels of CSF in the serum. Such mice tolerant to LPS were used as an experimental tool to identify the CSF-producing cells which respond to LPS. We observed that generation of LPS-induced CSF in mice tolerant to LPS could be restored by an intraperitoneal injection of spleen cells 24 h before the challenging injection of LPS. Depletion of the adherent cells from the spleen cells reduced the ability of the splenic lymphocytes to restore the capacity of the mice tolerant to LPS to generate serum CSF. Reconstitution of the splenic lymphocytes with 5% thioglycolate-elicited peritoneal macrophages, however, reestablished the restorative capacity of these cells, whereas almost no restoration was observed after direct injection of elicited peritoneal macrophages. These data suggest that the spleen cells are active in generating CSF, provided that macrophages are present and can interact with the splenic lymphocytes to generate LPS-induced CSF in the serum.
Alterations in the membrane of macrophages from leprosy patients
Authors: Birdi T J , Mistry N F , Mahadevan P R , Antia N H
Published: January 2020

Macrophage cultures pulsed with viable Mycobacterium leprae were assessed for erythrocyte rosetting in three groups of individuals, i.e., normal subjects, and tuberculoid and lepromatous patients. Of these, only the lepromatous group showed a reduction in rosetting ability after infection with M. leprae. The specificity of such a reduction pattern was confirmed by using various mycobacteria to infect the macrophages. A threshold effect was noted in all three groups. Although a reduction was obtained in the amount of rosetting of macrophages from lepromatous patients with 10(4) acid-fast bacilli per culture, tuberculoid and normal macrophages resisted such an effect with as large a dose as 20 X 10(6) to 30 X 10(6) and 30 X 10(6) bacilli per culture, respectively. The M. leprae-caused alterations in macrophages from lepromatous patients were reversible by treatment with trypsin and colchicine. Cytochalasin B and Tween 80 were unable to alter the pattern. Treatment of cells with neuraminidase was inconclusive since it enhanced rosetting values of both control and infected cultures. These manipulations were significant in elucidating the target point of the host (macrophage) and parasite (M. leprae) interaction and in delineation of the external and internal effects upon the macrophages. Both M. leprae and macrophages were participants in Fc reduction, as treatment of the former with rifampicin and of the latter with cyclocheximide significantly augmented the rosetting ability. In conclusion, it appears that M. leprae, upon entering a lepromatous macrophage, initiates the production of a protein which acts via the microtubules to alter membrane topography. It is possible that the altered membrane prevents effective macrophage-lymphocyte interaction. This could be one of the mechanisms by which cell-mediated immunity is suppressed in lepromatous leprosy.
Reduction of the secretory response to Escherichia coli heat-stable enterotoxin by thiol and disulfide compounds
Authors: Greenberg R N , Dunn J A , Guerrant R L
Published: January 2020

We examined the effects of disulfide and thiol compounds on Escherichia coli heat-stable enterotoxin (ST) and cyclic GMP-induced secretion. Both cystamine and cystine (disulfide compounds) reduced the secretory responses to submaximal doses of ST in suckling mice (at 0.5 mumol per mouse) and reduced ST activation of guanylate cyclase (by 33 to 73% at 1 mM). In higher doses, cystamine completely eradicated a maximally effective ST dose as well. In addition, the sulfhydryl (thiol) compounds cysteamine, cysteine, and acetylcysteine strikingly reduced the secretory response and the guanylate cyclase response to ST. Neither the disulfide nor the thiol compounds tested reduced cyclic GMP-induced secretion. These studies suggest that disulfide and thiol compounds both block ST-induced secretion before its activation of guanylate cyclase. Taken with the work of others, these findings suggest that disulfide compounds may alter the oxidation reduction state of a cell or act directly on the guanylate cyclase enzyme, whereas thiol compounds may inactivate ST itself by breaking its disulfide bridges, or it may alter guanylate cyclase activation by ST. Both families of compounds deserve further consideration among potential antisecretory agents for application in the control of ST-induced diarrhea.
Physical and biological properties of U.S. standard endotoxin EC after exposure to ionizing radiation
Authors: Csako G , Elin R J , Hochstein H D , Tsai C M
Published: January 2020

Techniques that reduce the toxicity of bacterial endotoxins are useful for studying the relationship between structure and biological activity. We used ionizing radiation to detoxify a highly refined endotoxin preparation. U.S. standard endotoxin EC. Dose-dependent changes occurred by exposure to 60Co-radiation in the physical properties and biological activities of the endotoxin. Sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis showed gradual loss of the polysaccharide components (O-side chain and R-core) from the endotoxin molecules. In contrast, although endotoxin revealed a complex absorption pattern in the UV range, radiation treatment failed to modify that pattern. Dose-related destruction of the primary toxic component, lipid A, was suggested by the results of activity tests: both the pyrogenicity and limulus reactivity of the endotoxin were destroyed by increasing doses of radiation. The results indicate that the detoxification is probably due to multiple effects of the ionizing radiation on bacterial lipopolysaccharides, and the action involves (i) the destruction of polysaccharide moieties and possibly (ii) the alteration of lipid A component of the endotoxin molecule.
Inhibition of host cell catalase by Mycoplasma pneumoniae: a possible mechanism for cell injury
Authors: Almagor M , Yatziv S , Kahane I
Published: January 2020

This study demonstrates that viable Mycoplasma pneumoniae cells inhibit catalase activity in several types of intact human cells as well as in solution. Human erythrocyte catalase was inhibited up to 72%, and the inhibition of catalase in human cultured skin fibroblasts, lung carcinoma epithelial cells, and ciliated epithelial cells from human nasal polyps ranged between 75 and 80%. UV light-killed mycoplasmas failed to inhibit catalase activity both in intact cells and in vitro. After M. pneumoniae infection of human cultured skin fibroblasts, the level of malonyldialdehyde, an indicator for membrane lipid peroxidation, was 3.5 times higher than in control fibroblasts. Virulent M. pneumoniae completely inhibited catalase activity in solution, whereas the nonvirulent strains had a lesser ability to inhibit catalase activity. These findings suggest that as a result of host cell catalase inhibition by M. pneumoniae, the toxicity of the hydrogen peroxide generated by the microorganism and the affected cell is enhanced, thereby inducing host cell damage.
Escherichia coli lipopolysaccharides diminish and enhance cell function of human polymorphonuclear leukocytes
Authors: Henricks P A , van der Tol M E , Thyssen R M , van Asbeck B S , Verhoef J
Published: January 2020

The effects of the lipopolysaccharide (LPS) of Escherichia coli J5 and 0111B4 on the function of human polymorphonuclear leukocytes (PMN) were tested. E. coli J5 is a UDP-galactose-4-epimerase-deficient mutant of E. coli 0111B4, and its LPS, therefore, contains mainly lipid A, as it lacks the polysaccharide side chains. PMN which had been incubated with J5 LPS showed decreased phagocytic, chemotactic, and metabolic activities as compared with control PMN. In contrast, incubation of PMN with 0111B4 LPS had no effect or even an enhancing effect on PMN function. When lipid A and the polysaccharide fraction were isolated from 0111B4 LPS, it was shown that lipid A had the same deleterious effect on PMN function as did J5 LPS and that the LPS fraction had no effect. When PMN were incubated with J5 LPS or lipid A, it could be shown that these structures were able to induce PMN to generate superoxide and chemiluminescence. 0111B4 LPS and the polysaccharide component were able to generate a metabolic burst by the PMN to a lesser extent. The induced defects in PMN function by J5 LPS could be prevented when polymyxin B or an oxygen-radical scavenger was present. We hypothesize that the lipid A portion of LPS is toxic for PMN due to the induction of toxic oxygen species by the PMN. These toxic oxygen species destroy the phagocytic, chemotactic, and metabolic activities of the PMN.
Genetics of natural resistance to Sendai virus infection in mice
Authors: Brownstein D G
Published: January 2020

The genetics of resistance to a naturally occurring respiratory infection caused by Sendai virus was examined in F1, F2, and backcross progeny of resistant C57BL/6J and susceptible DBA/2J mice and in 25 recombinant inbred strains. An intranasal inoculum of 0.1 50% tissue culture infective dose (low dose) of Sendai virus caused 0% mortality in C57BL/6J and F1 mice and 73% mortality in DBA/2J mice. An inoculum of 1.0 50% tissue culture infective dose (high dose) caused 3, 0, and 89% mortality in C57BL/6J, F1, and DBA/2J mice, respectively. Low-dose infection caused 36% mortality in F1 X DBA/2J hybrids and 0% mortality in F2 hybrids. High-dose infection caused 29 and 32% mortality in F1 X DBA/2J and F2 hybrids, respectively. Resistance was not linked to H-2 haplotype, coat color, or sex. High-dose infection caused deaths in 12 recombinant inbred strains, and the strain distribution pattern was concordant with that of a chromosome 1 marker, Sas-1, in 20 of 25 strains (P less than 0.01). Resistance therefore behaved as a simple Mendelian dominant trait which presumptively mapped to chromosome 1.
Association of fimbriae with the hydrophobicity of Streptococcus sanguis FC-1 and adherence to salivary pellicles
Authors: Gibbons R J , Etherden I , Skobe Z
Published: January 2020

A nonhydrophobic mutant of Streptococcus sanguis FC-1 was isolated which has a greatly diminished capacity for attaching to experimental salivary pellicles on hydroxyapatite surfaces and for aggregating with salivary components. The mutant appears to be defective in the synthesis of fimbriae, as judged by electron microscopic observations and by its inability to exhibit twitching motility.
Effects of alpha-amylase on in vitro growth of Legionella pneumophila
Authors: Bortner C A , Miller R D , Arnold R R
Published: January 2020

Sterile parotid saliva inhibited growth of Legionella pneumophila on solid media, and the salivary component involved in this inhibition has been shown to be amylase. Disk diffusion and well plate assays were used to study possible mechanisms for this effect. The amylolytic activity of saliva copurified with inhibitory activity, and both activities were sensitive to proteinase K digestion and heat treatment. In addition, purified alpha-amylase from several sources (bacteria, fungi, porcine pancreas, and human saliva) exhibited similar activity. Incorporation of charcoal or bovine serum albumin into media blocked inhibition by amylase. Replacement of Bacto-Agar with Noble agar (both from Difco Laboratories) prevented growth inhibition in the absence of starch. However, when corn starch was present with Noble agar, amylase-induced growth inhibition occurred. Purification of starch by washing with methanol eliminated some toxic component. The toxic component from starch could be recovered from the methanol wash and inhibited growth of L. pneumophila in the absence of amylase activity. The results suggest that toxic substances exist in media components which may be unmasked during salivary amylase digestion of starch. This effect may explain, in part, the difficulty in recovery of the organism from clinical specimens containing amylase.
Immune serum-mediated effects on brucellosis evolution in mice
Authors: Plommet M , Plommet A M
Published: January 2020

Immune serum injected into mice before a footpad challenge of virulent strain Brucella abortus 544 can prevent dissemination of infection to the spleen. Sera from mice infected with Brucella for at least 2 months or from mice vaccinated with a protein-bound cell wall peptidoglycan Brucella fraction completely stopped dissemination. Brucella lipopolysaccharide and polysaccharide cross-reacting Yersinia immune sera reduced dissemination. Both peptidoglycan and lipopolysaccharide immune sera injected simultaneously with an intravenous challenge caused a shift in Brucella from spleen to liver. When immune sera were injected simultaneously with an intravenous challenge, the kinetics of splenic infection showed two effects: an early one, optimally measured at day 7 postchallenge, showed reduced numbers in the spleen due to the shift of Brucella to the liver; a late effect, measured at day 21 postchallenge, showed reduced numbers in spleen and liver with nearly complete clearance by day 49 postchallenge. Brucella lipopolysaccharide and cross-reacting bacterial antisera induced the early effect only, whereas peptidoglycan and infected mouse sera induced both effects. When peptidoglycan immune serum was injected 2 or 7 days after intravenous challenge, the late effect was somewhat reduced. Hence, immune sera to protein and polysaccharide surface antigens can (i) prevent dissemination of systemic infection and (ii) help destroy intercellular bacteria (protein antigen only). These effects may represent a large part of vaccinal immunity.
Modulation of Bordetella pertussis by nicotinic acid
Authors: McPheat W L , Wardlaw A C , Novotny P
Published: January 2020

Growth of Bordetella pertussis in a high concentration of nicotinic acid (NA) had a modulating effect on several properties and activities of the bacteria. Compared with normally grown cells, those grown in a high concentration of NA had reduced capacity for taking up both NA and nicotinamide (ND); they had reduced adenylate cyclase activity and showed loss of agglutinogen factors 2 and 3, but an increase in factor 1. By contrast, cells grown in a high concentration of ND showed only a slightly decreased capacity for uptake of ND and none of the other changes. Modulation of B. pertussis by NA varied with the strain and culture conditions and appeared to be distinct from the antigenic modulation induced by high Mg2+ in the culture medium. Evidence is presented for the association of a small proportion of the extracytoplasmic adenylate cyclase with the outer membrane of B. pertussis.
Hemagglutinin-specific antibody responses in immunoglobulin G, A, and M isotypes as measured by enzyme-linked immunosorbent assay after primary or secondary infection of humans with influenza A virus
Authors: Burlington D B , Clements M L , Meiklejohn G , Phelan M , Murphy B R
Published: January 2020

The isotype-specific antibody responses to purified hemagglutinin of adults undergoing either primary or secondary infection with an influenza A virus were characterized by using an enzyme-linked immunosorbent assay. Twenty-eight military recruits undergoing primary infection with A/USSR/92/77 (H1N1)-like virus had serum antibody rises in the immunoglobulin M (IgM) (86%), IgG (100%), and IgA (96%) isotypes. In contrast, 19 adult volunteers undergoing secondary infection with A/Peking/2/79 (H3N2) wild-type virus had serum antibody titer rises largely restricted to the IgG (68%) and IgA (74%) classes, with only 1 volunteer having a serum IgM antibody titer rise. Nasal wash hemagglutinin-specific antibody responses in the adults undergoing secondary infection were predominantly in the IgA class (74%). There was a correlation between the presence of and the magnitude of nasal wash and serum hemagglutinin-specific IgA antibody responses in these adults. This suggested that there was a common source for the hemagglutinin-specific local IgA antibody and serum IgA antibody produced after infection. The recruits undergoing primary H1N1 influenza virus infection had H1 hemagglutinin-specific enzyme-linked immunosorbent assay antibody in each of the IgA, IgG, and IgM isotypes in their acute-phase serum. However, no role for this cross-reactive antibody in modifying the severity of illness experienced by the recruits could be demonstrated.
Inhibition of macromolecular synthesis in cultured rabbit cells by Treponema pallidum (Nichols)
Authors: Wong G H , Steiner B M , Graves S
Published: January 2020

Treponema pallidum partially inhibited the synthesis of DNA, RNA, and protein by rabbit cells in vitro. The inhibition of DNA synthesis was proportional to treponemal concentration and persisted during the period of exposure to T. pallidum. The toxic effect was not dependent on treponemal metabolism or on whole treponemes, since heat- and penicillin-killed treponemes and a cell-free sonicate of treponemes had similar toxicities. The toxic factor(s) was also detected in extracts of syphilitic rabbit testes but not in extracts of normal rabbit testes or testes inflamed by chemical means. The T. pallidum-derived toxic material had a molecular weight greater than 20,000 as determined by dialysis. Protein and DNA synthesis were most rapidly inhibited; RNA synthesis continued at normal rates for up to 2 h after exposure to treponemes. Protein synthesis or a necessary precursor of protein synthesis appeared to be the primary target of the T. pallidum toxin(s).
Mechanisms of enhanced resistance of Mycobacterium bovis BCG-treated mice to ectromelia virus infection
Authors: Sakuma T , Suenaga T , Yoshida I , Azuma M
Published: January 2020

The mechanism of enhanced resistance of Mycobacterium bovis BCG-treated mice to ectromelia virus infection was investigated by determining the effect of splenectomy, antithymocyte serum, and antimacrophage serum on resistance. It was greatly reduced by these treatments, not only in normal mice, but also in mice treated with live or heat-inactivated BCG. Production of circulating interferon by ectromelia virus and Newcastle disease virus was augmented in BCG-treated mice and was markedly depressed by splenectomy and antithymocyte and antimacrophage serum treatments in both BCG-treated and normal mice. Carbon clearance activity was activated in BCG-treated mice, but splenectomy did not influence phagocytic activity. These results suggest that augmented interferon production in the spleens of BCG-treated mice plays a major role in enhanced resistance. Other possible mechanisms are discussed.
Reactivity and immunogenicity of bivalent (AC) and tetravalent (ACW135Y) meningococcal vaccines containing O-acetyl-negative or O-acetyl-positive group C polysaccharide
Authors: Vodopija I , Baklaic Z , Hauser P , Roelants P , André F E , Safary A
Published: January 2020

The immunogenicity and the reactivity of two bivalent (AC) and two tetravalent (ACW135Y) meningococcal vaccines containing either the O-acetyl-positive or the O-acetyl-negative group C polysaccharide were compared in healthy adolescent and adult volunteers. The vaccines contained high-molecular-weight, purified capsular meningococcal polysaccharides and were administered subcutaneously at a dose of 50 micrograms for each polysaccharide. Reactivity was low for all vaccines, and the tetravalent vaccines were not significantly more reactive than the bivalent vaccines. Immunogenicity was measured by assay of bactericidal antibodies in pre- and postvaccination sera. More than 90% of the vaccines had at least a fourfold increase in the bactericidal antibody titer against each group of meningococcus represented in the vaccines. Addition of polysaccharide W135 and polysaccharide Y to polysaccharides A and C did not alter the immunogenicity of the latter polysaccharides. Thus, there is no evidence of antigenic competition with the tetravalent vaccine. Comparison of the antibody response to the O-acetyl-positive and the O-acetyl-negative variants of group C polysaccharide in the bivalent vaccines, as measured by both bactericidal and enzyme-linked immunosorbent assays, indicates that in adults, the two types of group C polysaccharide are similarly immunogenic.
Purification and immunochemical characterization of Streptococcus sanguis ATCC 10557 serotype II carbohydrate antigen
Authors: Koga T , Okahashi N , Yamamoto T , Mizuno J , Inoue M , Hamada S
Published: January 2020

Cell wall carbohydrate antigen of Streptococcus sanguis ATCC 10557 (serotype II/biotype B) was extracted from purified cell walls by treatment with 5% trichloroacetic acid at 4 degrees C for 8 h. The extract was purified by chromatography on DEAE-Sephadex A-25 and Sephadex G-100 columns. The purified carbohydrate antigen produced a single precipitin band against anti-type II serum, which fused with the band produced by the autoclaved extract or the phenol-water extract of the S. sanguis cells. The type II antigen was a polysaccharide composed of glucose, galactose, rhamnose, and N-acetylgalactosamine in a molar ratio of approximately 3:6:3:2. Quantitative precipitin inhibition tests with various haptenic sugars indicated that N-acetylgalactosamine was a major determinant of the type II antigen.
Activation of chicken alternative complement pathway by fowlpox virus-infected cells
Authors: Ohta H , Kai C , Yoshikawa Y , Yamanouchi K
Published: January 2020

Fresh normal chicken serum (NCS) which lacked virus-neutralizing antibody to fowlpox virus (FPV) was found to inhibit the appearance of the cytopathic effect of the virus, virus growth, and plaque formation in chicken embryo cells. Immunofluorescent examination revealed the deposition of the third component of complement (C3) on FPV-infected chicken embryo cells incubated with fresh NCS. The inhibitory activity of fresh NCS on viral cytopathic effect was independent of the Ca2+ ion and was abrogated by treatment of fresh NCS with inulin or zymosan. Similarly, deposition of C3 on FPV-infected cells occurred independently of the Ca2+ ion and was inhibited by treatment of fresh NCS with inulin or zymosan but was not inhibited by absorption with FPV-infected cells. These results suggest that antibody-independent activation of complement by FPV-infected cells via the alternative pathway caused the inhibition of the virus growth as well as the C3 deposition. Involvement of complement activation as nonspecific host response to virus infection was also suggested by the demonstration of the C3 deposition in the skin lesions of FPV-infected chickens.
Protective effect of poly-2-vinylpyridine-N-oxide on susceptibility of silica-treated mice to experimental histoplasmosis
Authors: Von Behren L A , Chaudhary S , Rabinovich S , Shu M D , Tewari R P
Published: January 2020

We have studied the ability of poly-2-vinylpyridine-N-oxide (PVNO), a lysosomal stabilizing agent, to abrogate the cytotoxic effects of silica on macrophages. Male C3H/HeN mice were pretreated with PVNO and inoculated intravenously with silica particles. At 24 h after silica injection, silica-treated and -untreated mice were challenged intravenously with varying doses of live yeast cells of Histoplasma capsulatum. All mice receiving silica died when challenged with 5 X 10(5) yeast cells of Histoplasma sp. compared with no deaths in PVNO-pretreated animals and 10% mortality in controls not receiving PVNO or silica. When animals were given 2.5 X 10(5) yeast cells (a sublethal dose), the protective effect of PVNO was seen by a reduction in splenomegaly and viable Histoplasma sp. present in the spleen. Furthermore, PVNO alone showed a significant protective effect (P less than 0.05) against a lethal challenge with Histoplasma sp. Prior treatment with PVNO also protected mouse peritoneal macrophages from the cytotoxic effects of silica particles in vitro. These results indicate that PVNO abrogates the cytotoxicity of silica particles on macrophages and also increases the resistance of mice to histoplasmosis.
Soluble peptidoglycan from Staphylococcus aureus is a murine B-lymphocyte mitogen
Authors: Babu U M , Zeiger A R
Published: January 2020

Soluble peptidoglycan from Staphylococcus aureus has been shown to be capable of causing murine B lymphocytes from the spleen to proliferate and to secrete immunoglobulins in both an in vitro and an in vivo assay. The optimal concentration in vitro was between 33 and 100 micrograms/ml. A 3-day incubation with soluble peptidoglycan was more stimulatory than was a 1- or 2-day incubation. Removal of most of the T lymphocytes with anti-theta serum did not result in any significant change in the mitogenic activity of soluble peptidoglycan on the remaining B cells.
Detection of anti-teichoic acid immunoglobulin G antibodies in experimental Staphylococcus epidermidis endocarditis
Authors: West T E , Cantey J R , Apicella M A , Burdash N M
Published: January 2020

An enzyme-linked immunosorbent assay (ELISA) was developed for the detection of rabbit immunoglobulin G (IgG) antibodies to purified cell wall teichoic acids from the Staphylococcus aureus Lafferty strain and three strains of coagulase-negative staphylococci. Significant immunological cross-reactivity occurred only between the teichoic acid of S. aureus and one coagulase-negative preparation. The ELISA was used to determine the serum IgG response to Staphylococcus epidermidis in a rabbit model of aortic valve endocarditis. Blood samples were drawn before inoculation and then every 5 days until death or sacrifice at 32 to 35 days postinoculation. Valve vegetations were culture positive at autopsy in 16 (59%) of the 27 catheterized rabbits. Antibody titers in this culture-positive group and the culture-negative group began to rise as early as day 6. Although both groups demonstrated an antibody response, the culture-positive group attained a significantly higher titer on days 26 and 31. Antibodies also rose in a control group of rabbits without a heart catheter but which were inoculated with bacteria. Again, the antibody titer was significantly less than that for the culture-positive group. This ELISA may be useful for the diagnosis of coagulase-negative staphylococcal infections in humans.
Lysis of herpesvirus-infected cells by macrophages activated with free or liposome-encapsulated lymphokine produced by a murine T cell hybridoma
Authors: Koff W C , Showalter S D , Seniff D A , Hampar B
Published: January 2020

Thioglycolate-induced mouse peritoneal macrophages were activated in vitro by the lymphokine designated macrophage-activating factor (MAF) produced by a murine T cell hybridoma to lyse herpes simplex virus type 2 (HSV-2)-infected murine target cells. Comparison of uninfected BALB/c 10E2 cells with HSV-2-infected 10E2 cells showed that macrophages activated with MAF selectively destroyed HSV-2-infected cells and left uninfected cells unharmed, as measured by an 18-h 51Cr-release assay. In contrast, macrophages treated with medium were as efficient as MAF-activated macrophages in suppressing the production of HSV-2 from virus-infected cells. These findings suggest that macrophages must attain an activated state to lyse HSV-2-infected cells. Finally, incubation of macrophages with liposomes containing MAF was shown to be a highly efficient method for activation of macrophages against HSV-2 infected cells. The ability to selectively destroy herpesvirus-infected cells in vitro by macrophages activated with liposome-encapsulated MAF suggests that the therapeutic efficacy of this treatment in vivo should be evaluated.
Lymphokine-mediated inhibition of Chlamydia replication in mouse fibroblasts is neutralized by anti-gamma interferon immunoglobulin
Authors: Byrne G I , Krueger D A
Published: January 2020

Experiments were carried out to characterize immunologically mediated chlamydial persistence in cell culture. Mouse fibroblasts were activated to restrict Chlamydia psittaci 6BC replication by including mitogen (concanavalin A)-induced spleen cell supernatant fluids from immunized animals in the growth medium. When mouse fibroblasts were incubated with lymphokine for 24 h before infection and then with growth medium after infection (preinfection treatment), chlamydial replication was delayed but eventually detected. No substantial chlamydial growth occurred, even with extended incubation times when mouse fibroblasts were continuously exposed to lymphokine before and after infection. Low levels of infectious chlamydiae were produced in preinfection-treated mouse fibroblasts but not in mouse fibroblasts subjected to continuous lymphokine exposure. Incubation of lymphokine with anti-murine gamma interferon immunoglobulin neutralized the observed lymphokine-mediated activity, but incubation in the presence of anti-murine alpha plus beta interferon serum did not alter lymphokine activity. We conclude that the lymphokine components responsible for activating fibroblasts to restrict C. psittaci replication exhibits properties similar to gamma interferon.
Immune response to porin in cattle immunized with whole cell, outer membrane, and outer membrane protein antigens of Brucella abortus combined with trehalose dimycolate and muramyl dipeptide adjuvants
Authors: Winter A J , Verstreate D R , Hall C E , Jacobson R H , Castleman W L , Meredith M P , McLaughlin C A
Published: January 2020

The immune response of cattle to nonliving vaccines derived from Brucella abortus rough strain 45/20 was studied. Vaccines contained trehalose dimycolate and a derivative of muramyl dipeptide. N-acetylmuramyl-L-alpha-aminobutyryl-D-isoglutamine. A factorial experiment was designed to test the effects of type of antigen, quantity of antigen, and quantity of mineral oil on the immune response to porin. Muramyl dipeptide was kept constant at 5 mg per dose, and 1 part of trehalose dimycolate was incorporated for two parts of dry matter. Over a 10-week period, blastogenesis responses to porin were largest in cattle immunized with outer membranes; the highest antibody titers to the porin-lipopolysaccharide complex were achieved by immunization with detergent-extracted outer membrane proteins. There was no advantage in the use of 25, rather than 5, mg of any of the antigens, but antibody responses were improved by increasing the quantity of oil from 0.6 to 1.8 ml per dose. In other animals, blastogenesis and antibody responses were sustained at high levels longer than 3 months after two vaccinations with outer membrane proteins. Intradermal injection of porin evoked inflammatory reactions histologically consistent with delayed-type hypersensitivity. Cross-reactions in cases of delayed-type hypersensitivity occurred with porin derived from a smooth strain of B. abortus but were less extensive than in the blastogenesis test. The magnitude of the delayed-type hypersensitivity and blastogenesis responses induced by vaccination exceeded those observed after natural or experimental infections. No ill effects were observed after vaccination. These findings provide a basis for the use of trehalose dimycolate and muramyl dipeptide adjuvants in evaluating nonviable vaccines for bovine brucellosis.
Stimulation of chemiluminescence and resistance against aerogenic influenza virus infection by synthetic muramyl dipeptide combined with trehalose dimycolate
Authors: Masihi K N , Brehmer W , Azuma I , Lange W , Müller S
Published: January 2020

The effect on respiratory burst of splenic cells from mice pretreated with oil-in-water emulsions of muramyl dipeptide (MDP), trehalose dimycolate (TDM), or the combination of MDP with TDM was studied by luminol-dependent chemiluminescence in response to stimulation by zymosan. Spleen cells from mice pretreated with TDM, but not those of mice treated with MDP, generated increased chemiluminescence. Spleen cells from animals pretreated with the combination of MDP and TDM exhibited markedly enhanced chemiluminescence activity. The effect of enhanced activity of preparations containing MDP combined with TDM was further examined in vivo by an aerosol infection of pretreated mice with a mouse-pathogenic influenza virus. Pretreatment with 6-O-acyl analogs and one ubiquinone derivative of MDP alone did not induce any resistance against influenza virus. Significant protection was conferred only when MDP and certain analogs were combined with TDM. The enhancement of nonspecific resistance to influenza virus infection was related to the chemical structure of the synthetic immunostimulant. A greater degree of protection was induced by the combination of TDM with the lipophilic derivatives like B 30-MDP and L-18 MDP.
Plasmodium falciparum: protein antigens identified by analysis of serum samples from vaccinated Aotus monkeys
Authors: Kan S C , Yamaga K M , Kramer K J , Case S E , Siddiqui W A
Published: January 2020

Serum samples from Aotus trivirgatus subsp. griseimembra monkeys obtained at different stages of a vaccination experiment were analyzed for total antibody titer to Plasmodium falciparum and were used for identifying protective antigens of the human malaria parasite. Total malarial antibody titers were higher in serum samples from protected monkeys (vaccinated with antigen in an adjuvant) than in those from unprotected monkeys (vaccinated with either antigen or adjuvant only). Parasite proteins were labeled with [3H]isoleucine, solubilized with nonionic detergent, and reacted with immune Aotus sera. Immunoprecipitates obtained were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography. Thirteen protein antigen bands in the molecular weight range 73,000 to 180,000 were resolved. Serum samples obtained from protected Aotus monkeys reacted more intensely with these proteins than samples from unprotected monkeys did. Evidence is presented that the protective antigen is not a single, normally nonimmunogenic, protein that is recognized only in protected monkeys. Rather, the present data indicate that a heightened immune response to multiple proteins correlated with in vivo protection to P. falciparum in Aotus monkeys. This finding may have a significant bearing on strategies for the development of a human P. falciparum vaccine.
Inhibition of mouse peritoneal macrophage DNA synthesis by infection with the arenavirus Pichinde
Authors: Friedlander A M , Jahrling P B , Merrill P , Tobery S
Published: January 2020

Macrophage DNA synthesis and proliferation occur during the development of cell-mediated immunity and in the early nonspecific reaction to infection. Arenaviruses have a predilection for infection of cells of the reticuloendothelial system, and in this study we have examined the effect of the arenavirus Pichinde on macrophage DNA synthesis. We have found that infection of mouse peritoneal macrophages with Pichinde caused a profound dose-dependent inhibition of the DNA synthesis induced by macrophage growth factor-colony stimulating factor. At a multiplicity of inoculum of 5, there is a 75 to 95% inhibition of DNA synthesis. Viable virus is necessary for inhibition since Pichinde inactivated by heat or cobalt irradiation had no effect. Similarly, virus pretreated with an antiserum to Pichinde was without inhibitory effect. Inhibition was demonstrated by measuring DNA synthesis spectrofluorometrically as well as by [3H]thymidine incorporation. The inhibition of DNA synthesis was not associated with any cytopathology. There was no evidence that the inhibition was due to soluble factors, such as prostaglandins or interferon, released by infected cells. These studies demonstrate, for the first time in vitro, a significant alteration in macrophage function caused by infection with an arenavirus. It is possible that inhibition of macrophage proliferation represents a mechanism by which some microorganisms interfere with host resistance.
Trypanosoma rhodesiense infection in mice: sex dependence of resistance
Authors: Greenblatt H C , Rosenstreich D L
Published: January 2020

There is large variation in the survival of inbred mouse strains infected with Trypanosoma rhodesiense (EATRO 1886). Of those strains that survived for at least 22 days postinfection, female mice were markedly more resistant than male mice. The longer a strain survived, the greater was the difference in survival between male and female mice. Parasite counts were higher in male mice than in females, suggesting that the decreased resistance of males was due to their relative inability to control parasite growth. To determine the possible role of an X-linked resistance gene, resistant (C57BL/6) and susceptible (BALB/c) mice were mated, and their F1 progeny were infected with T. rhodesiense. There was no difference in the resistance between reciprocal F1 male mice (C57BL/6 X BALB/c versus BALB/c X C57BL/6), indicating that an X-linked gene does not account for the difference in resistance between susceptible and resistant mice.