bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunization with purified protein antigens from Streptococcus mutans against dental caries in rhesus monkeys
Authors: Lehner T , Russell M W , Caldwell J , Smith R
Published: January 2020

Protein antigens I, I/II, II, and III were prepared from Streptococcus mutans (serotype c). Their immunogenicities and protective effects against dental caries were investigated in 40 rhesus monkeys kept entirely on a human-type diet, containing about 15% sucrose. Antigens I, I/II and, to a lesser extent, antigen II induced significant reductions in dental caries, as compared with sham-immunized monkeys. This was achieved with 1 or 2 doses of antigen, the first of which was administered with adjuvant (Freund incomplete adjuvant or aluminum hydroxide). There was no reduction in caries in monkeys immunized with antigen III. The reduction in caries in the animals immunized with antigens I or I/II was comparable to that in monkeys immunized with whole cells. Protection against caries was associated predominantly with serum and gingival crevicular fluid immunoglobulin G antibodies, which appeared to be directed against the antigen I determinant, but antibodies to antigen II, though not to antigen III, were also protective.
Cytomegalovirus-specific cytotoxicity mediated by non-T lymphocytes from peripheral blood of normal volunteers
Authors: Kirmani N , Ginn R K , Mittal K K , Manischewitz J F , Quinnan G V
Published: January 2020

The cytotoxicity of circulating mononuclear cells from normal volunteers was determined using human leukocyte antigen (HLA)-typed, low-passaged human skin fibroblasts infected with cytomegalovirus as target cells. Peripheral blood lymphocytes from both seropositive and seronegative individuals possessed virus specific cytotoxicity. Although all target cells used were susceptible to virus specific lysis, lymphocytes from some individuals were more active against some target cells than others. This differential cytotoxicity did not follow a consistent pattern of HLA restriction. Some variations in cytotoxic activity were noted on sequential studies of individual volunteers. Studies of fractionated lymphocytes from selected immune and nonimmune individuals demonstrated that cytotoxicity of lymphocytes from both groups was mediated by nonadherent, Fc receptor bearing cells which did not form rosettes with sheep erythrocytes. Repeated washing sometimes decreased cytotoxicity of lymphocytes from immune individuals, and addition of serum containing antibody to cytomegalovirus enhanced cytotoxicity, suggesting antibody dependence. It is concluded that cytotoxic lymphocytes from nonimmune volunteers possessed characteristics of natural killer cells, whereas those from immune volunteers probably consisted of both natural killer cells and antibody-dependent killer cells.
Evaluation of iron dextran and mucin for enhancement of the virulence of Yersinia enterocolitica serotype O:3 in mice
Authors: Smith R E , Carey A M , Damare J M , Hetrick F M , Johnston R W , Lee W H
Published: January 2020

The pathogenic role of Yersinia enterocolitica serotypes O:3, O:8, and O:9 in human infections is well documented. Whereas the virulence of the O:8 strains can be readily demonstrated in mice by 50% lethal dose determinations, the O:3 and O:9 strains have no lethal effect on mice by any route of inoculation. A mouse virulence test for the O:3 and O:9 strains is described. Y. enterocolitica strains were first tested for the presence of virulence-associated plasmid characteristics by auto-agglutination and gel electrophoresis procedures before mouse virulence determinations. The 50% lethal dose of the O:3 strains injected intraperitoneally with 2.5% mucin was about 10(7) colony-forming units. However, histological examinations showed that mucin allowed the growth of Y enterocolitica on the surface of the livers and spleens of the mice without internal lesions. The 50% lethal dose of the same O:3 strains injected intraperitoneally with 1 ml of 10% iron dextran in saline was about 10(5) to 10(6) colony-forming units, and the nonlethal infective dose with typical lesion development was 20 to 200 colony-forming units. The infected mice developed symptoms and extensive liver and spleen lesions which differed from those in mice infected intraperitoneally with the virulent O:8 strains. These results showed that the virulence of the O:3 Y. enterocolitica strains can be measured by intraperitoneal injection with iron dextran. This procedure was used to test the virulence of food isolates, plasmidless strains, and the effect of growth temperatures.
Resistance of peripheral autonomic neurons to in vivo productive infection by herpes simplex virus mutants deficient in thymidine kinase activity
Authors: Price R W , Khan A
Published: January 2020

We used a model involving acute and latent herpes simplex virus (HSV) infections of mouse superior cervical ganglia to assess in vivo neuronal infections with two thymidine kinase-deficient (TK-) mutants of HSV type 1. Despite replication of the TK- HSV strains at the site of inoculation in the eyes, little if any viral replication occurred in the superior cervical ganglia, as assessed by the viral titers of ganglion homogenates, viral antigens in tissue sections, and histopathological evidence of cytopathology or inflammation. Cyclophosphamide-induced immunosuppression and treatment with 6-hydroxydopamine, which enhanced productive infections of superior cervical ganglia with TK+ HSV did not induce TK- HSV ganglionic infections. Latent TK- HSV infections were not detected by cocultivation of ganglion explants. Efforts to infect ganglia in culture after they were removed from animals indicated that superior cervical ganglia, and particularly their neuronal elements, resisted productive TK- HSV infection. These results supported the hypothesis that viral thymidine kinase facilitates acute and reactivated productive HSV infections of neurons.
Alterations of pulmonary defense mechanisms by protein depletion diet
Authors: Jakab G J , Warr G A , Astry C L
Published: January 2020

Pulmonary defense mechanisms were quantitated in mice that were fed a protein-free diet (PFD) for periods of 2 and 3 weeks. Despite the severe weight loss and emaciation induced by the diet, the bactericidal mechanisms in their lungs were preserved against aerogenic challenges with staphylococcus aureus, Proteus mirabilis, and Listeria monocytogenes. Phagocytic assays of alveolar macrophages that were retrieved by pulmonary lavage from PFD-fed animals showed a decrease in Fc receptor-mediated binding activity but no alteration in the ingestion of sensitized erythrocytes. In contrast, the PFD induced defects in both the attachment phase and the engulfment phase of the phagocytic process when the challenge organism was Candida krusei. The PFD suppressed the pulmonary inflammatory response after mice were infected with influenza virus strain PR8; such mice also failed to eliminate infectious virus from their lungs. Virus infection in control mice suppressed pulmonary antibacterial defenses against challenges with S. aureus and P. mirabilis, and defect that was ameliorated in the lungs of PFD-fed mice with viral pneumonia. The data demonstrated that pulmonary defense mechanisms were modulated by a PFD but that the observed effect was dependent on the agent used to test host defenses.
Suppression of
Clostridium difficile
by Normal Hamster Cecal Flora and Prevention of Antibiotic-Associated Cecitis
Authors: Wilson Kenneth H. , Silva Joseph , Fekety F. Robert
Published: January 2020

Administration of normal cecal homogenates decreased numbers of viable
Clostridium difficile
and prevented cecitis in antibiotic-challenged hamsters. Cecal anaerobes appeared to suppress
C. difficile
.
Serological classification of Neisseria gonorrhoeae with monoclonal antibodies
Authors: Tam M R , Buchanan T M , Sandström E G , Holmes K K , Knapp J S , Siadak A W , Nowinski R C
Published: January 2020

Hybrid cells producing monoclonal antibodies against antigens of Neisseria gonorrhoeae were obtained by the polyethylene glycol-mediated fusion of mouse myeloma cells and lymphocytes from mice immunized with gonococcal protein I or outer membrane proteins. From four fusions, 16 phenotypically stable, independently cloned hybrid cell lines were selected for continued study. Each of the cell lines produced a characteristically different monoclonal antibody which reacted in immunoprecipitation assays with a unique antigenic determinant on protein I of the outer membrane complex of the bacteria. In antibody binding, immunofluorescence, and coagglutination assays these antibodies each reacted with a restricted group of N. gonorrhoeae strains. None of the monoclonal antibodies reacted with 17 other different species of Neisseria or with Branhamella catarrhalis. When tested on 34 N. gonorrhoeae reference serotyping strains, the monoclonal antibodies demonstrated serological relationships between the strains which paralleled those observed with conventional polyvalent antisera. These antibodies now provide standardized reagents for the rapid and precise serological characterization of many strains of N. gonorrhoeae.
Murine monoclonal antibodies specific for virulent Treponema pallidum (Nichols)
Authors: Robertson S M , Kettman J R , Miller J N , Norgard M V
Published: January 2020

Murine anti-Treponema pallidum (Nichols) lymphocyte hybridoma cell lines secreting monoclonal antibodies against a variety of treponemal antigens have been generated. Hybridomas isolated were of three major types: those that were directed specifically against T. pallidum antigens, those that were directed against treponemal group antigens (as evidenced by their cross-reactivity with T. phagedenis biotype Reiter antigens), and those that cross-reacted with both treponemal as well as rabbit host testicular tissue antigens. The majority (31 of 39 clones) of these anti-T. pallidum hybridomas, which produced monoclonal antibodies of mouse isotypes immunoglobulin G1 (IgG1), IgG2a, IgG2b, IgG3 or IgM, were directed specifically against T. pallidum and not other treponemal or rabbit antigens tested by radioimmunoassay. Four of these T. pallidum-specific hybridomas secreted monoclonal antibodies with greater binding affinity for "aged" rather than freshly isolated intact T. pallidum cells, suggesting a possible specificity for "unmasked" surface antigens of T. pallidum. Six anti-T. pallidum hybridomas produced complement-fixing monoclonal antibodies (IgG2a, IgG2b, or IgM) that were capable of immobilizing virulent treponemes in the T. pallidum immobilization (TPI) test; these may represent biologically active monoclonal antibodies against treponemal surface antigens. Three other hybridomas secreted monoclonal antibodies which bound to both T. pallidum and T. phagedenis biotype Reiter antigens, thus demonstrating a possible specificity for treponemal group antigens. Five hybridoma cell lines were also isolated which produced IgM monoclonal antibodies that cross-reacted with all treponemal and rabbit host testicular tissue antigens employed in the radioimmunoassays. This report describes the construction and characteristics of these hybridoma cell lines. The potential applications of the anti-T. pallidum monoclonal antibodies are discussed.
Macrophages in resistance to rickettsial infection: strains of mice susceptible to the lethal effects of Rickettsia akari show defective macrophage Rickettsicidal activity in vitro
Authors: Nacy C A , Meltzer M S
Published: January 2020

Activation of macrophages was assessed in strains of mice inoculated intraperitoneally with 1,000 times the 50% lethal dose of Rickettsia akari. Macrophages from mice resistant to R. akari infection (C3H/HeN, C57BL/10J, and BALB/cN) were nonspecifically tumoricidal 2 to 4 days after rickettsial inoculation. Moreover, these macrophages were microbial for R. akari in vitro; cells were resistant to infection with the bacterium and were capable of killing intracellular rickettsiae. In contrast, macrophages from strains of mice susceptible to R. akari (C3H/HeJ, C57BL/10SnCR, and A/J) failed to develop nonspecific tumoricidal activity over the course of lethal disease and became infected with R. akari in vivo within 2 days of rickettsial inoculation. Macrophages from uninfected mice of strains susceptible to R. akari also could not be activated for rickettsicidal or tumoricidal activities by treatment with macrophage-activating agents (Mycobacterium bovis BCG) in vivo or by treatment with lymphokines in vitro.
Phenoloxidase activity and virulence in isogenic strains of Cryptococcus neoformans
Authors: Rhodes J C , Polacheck I , Kwon-Chung K J
Published: January 2020

A naturally occurring Mel- variant of Cryptococcus neoformans was isolated from the wild type. The effect of phenoloxidase activity on virulence was analyzed on genetically constructed Mel+ and Mel- isolates. The traits Mel+ and virulence in mice, as measured by cumulative mortality and replication potential in brain tissue, cosegregated among the progeny of a Mel+ X Mel- cross. Revertants (MelR) isolated during the course of the cumulative mortality experiment were used to compare virulence in isogenic sets of Mel- and MelR. In two separate sets of such isolates, Mel+ phenotype and virulence coreverted. Measurement of substrate uptake and phenoloxidase activity showed that loss of detectable phenoloxidase was the basis for the Mel- phenotype and that enzyme activity reappeared in the MelR isolates. An intermediate phenotype, Melbg, was also described. Cosegregation and coreversion of the melanin phenotype and virulence suggest that phenoloxidase is a virulence factor in C. neoformans.
In vivo induction of anti-herpes simplex virus immune response by type 1 antigens and lipid A incorporated into liposomes
Authors: Naylor P T , Larsen H S , Huang L , Rouse B T
Published: January 2020

To establish the requirements for a potential subunit vaccine against herpes simplex virus (HSV), we analyzed the effects on immunogenicity of incorporating detergent-extracted glycoprotein-enriched HSV type 1 (HSV-1) antigens into liposomes alone or with the adjuvant lipid A. Incorporating HSV-1 antigens into liposomes enhanced their immunogenicity for antibody production as detected by radioimmunoassay. Antibody levels to free and liposome-bound antigens were enhanced by administering lipid A as an adjuvant. The maximum immunogenic effect was obtained by incorporating lipid A into liposomes containing the HSV-1 proteins. Such liposomes induced secondary antibody responses higher than those engendered by virus infection. Whereas infectious virus induced cell-mediated immunity detectable by the delayed-type hypersensitivity reactions and cytotoxic T lymphocyte production, none of the liposome preparations induced cell-mediated immunity.
Mechanism of hemolysis by Renalin, a CAMP-like protein from Corynebacterium renale
Authors: Bernheimer A W , Avigad L S
Published: January 2020

Synergistic hemolysis of sheep erythrocytes caused by Staphylococcus aureus and Corynebacterium renale resulted from the combined action of extracellular staphylococcal sphingomyelinase C and a newly described extracellular agent of C. renale (renalin). The affinity of renalin for ceramide was considered to play a key role in causing hemolysis in erythrocytes in which ceramide had been generated through the action of sphingomyelinase C.
Emetic action of staphylococcal enterotoxin A on weanling pigs
Authors: Taylor S L , Schlunz L R , Beery J T , Cliver D O , Bergdoll M S
Published: January 2020

Peroral and intraduodenal administration of staphylococcal enterotoxin A (SEA) to weanling pigs elicited an emetic response. Peroral administration of an emetic dose of SEA resulted in a single emetic episode occurring 90 to 180 min after dosing. Intraduodenal administration via a surgically implanted catheter of 100 or 150 micrograms of SEA resulted in multiple emetic episodes occurring 150 to 210 min after dosing, suggesting an intestinal site of action for SEA. The 50% emetic dose for perorally administered SEA was between 40 and 50 micrograms for 4.1- to 9.1-kg weanling pigs and 20 micrograms in 0.9- to 2.3-kg weanling pigs. Neurobehavioral responses, including alternating periods of drowsiness and restlessness, staggering, temporary loss of the righting reflex, and refusal to feed were also observed in pigs given an oral dose of SEA. Based on the demonstrated responsiveness of pigs to SEA, pigs should be considered suitable animal models for studies on the sites and mode of action of the toxin.
Purification and properties of glucosyltransferase responsible for water-insoluble glucan synthesis from Streptococcus mutans
Authors: Fukui K , Moriyama T , Miyake Y , Mizutani K , Tanaka O
Published: January 2020

A glucosyltransferase responsible for water-insoluble glucan synthesis was purified from the culture fluids of Streptococcus mutans 6715-15 strain by column chromatography on Toyopearl HW-60 and subsequently on hydroxyapatite. The enzyme preparation gave a single band on analysis by polyacrylamide gel electrophoresis. The pH dependency of the activity showed two optimal peaks at 5.8 and 7.3 and the Km values for sucrose were 1.4 and 3.3 mM at the respective optimal pHs. The molecular weight determined by sodium dodecyl sulfate gel electrophoresis was 180,000. Although the enzyme scarcely synthesized water-insoluble and water-soluble glucans from sucrose, water-insoluble glucan formed from sucrose in the presence of dextran T10 consisted of over 93% alpha-1, 3-glucosidic linkage. Analysis of the structure of water-insoluble glucan indicated that the enzyme catalyzed the formation of branch points in alpha-1,6-glucan (dextran) and transferred the glucosyl moiety of sucrose to the C-3 position of the branching glucose residue of dextran. Since this enzyme has not yet been registered, we named it mutansynthetase (EC 2.4.1.?).
Biological activity of a lipopolysaccharide extracted from Treponema hyodysenteriae
Authors: Nuessen M E , Birmingham J R , Joens L A
Published: January 2020

A lipopolysaccharide (LPS) was obtained from pathogenic Treponema hyodysenteriae by hot phenol-water extraction. Various effects of the LPS on host cells were examined in vitro. Toxicity for mouse peritoneal macrophages was observed after 10 h of incubation at concentrations as low as 15 micrograms of the LPS per ml. Marked enhancement of both complement (C3) and immunoglobulin G-Fc receptor-mediated internalization was noted in macrophages obtained from mice injected 6 days previously with 75 micrograms of the material. Incorporation of [3H]thymidine into murine splenocytes was elevated approximately fourfold when splenocytes were treated with 5 to 10 micrograms of LPS per ml. Incubation of the LPS with normal porcine serum resulted in the generation of a factor(s) that stimulated the migration of porcine leukocytes. Generation of the chemotactic activity was inhibited by heating the serum at 56 degrees C for 30 min before treatment with LPS. The results suggest that T. hyodysenteriae contains an LPS that is biologically active.
Evidence for a protective role of interferon in resistance to murine cytomegalovirus and its control by non-H-2-linked genes
Authors: Grundy J E , Trapman J , Allan J E , Shellam G R , Melief C J
Published: January 2020

Murine cytomegalovirus (MCMV) induces rapid production of a partially pH 2-stable type 1 interferon, the serum level of which is controlled by non-H-2-linked host genes. The production of high, intermediate, and low levels of interferon was found in C3H/He, C57BL/10, and BALB/c mice, respectively, and the use of H-2 congenic mice on the BALB/c or C57BL/10 background showed that H-2-associated genes were not involved. Administration of large (up to 200,000 U) daily doses of partially purified type 1 (alpha plus beta) interferon failed to protect low-producer BALB/c or BALB.K strains from lethal infection. Treatment of the higher (C3H/He) or intermediate (C57BL/10) producer strains with anti-type 1 interferon antibody significantly reduced their resistance to the virus; however, such treatment had no effect on the low-producer BALB/c strain. The decreased resistance of anti-interferon-treated C3H/He mice was accompanied by a transient reduction in serum interferon titers, decreased activation of natural killer cells, a markedly enhanced viremia, and increased viral titers in the liver. These data strongly support a protective role of interferon in defense against MCMV in certain strains of mice. Furthermore, these data suggest that previous observations of a correlation of non-H-2-linked, genetically determined resistance to MCMV with activation of natural killer cells may have its basis in the genetic control of interferon induction by MCMV.
Strains of Neisseria meningitidis isolated from patients and their close contacts
Authors: Frasch C E , Mocca L F
Published: January 2020

Neisseria meningitidis isolates from contacts, mostly family members, of 27 unrelated meningococcal disease patients were examined by serogrouping, serotyping, and a recently described sodium dodecyl sulfate-polyacrylamide gel electrophoresis typing procedure. Most of the isolates were serogroup B or C. Serotyping and sodium dodecyl sulfate-polyacrylamide gel electrophoresis typing now provide a more precise means than serogrouping for determining the epidemiological relationships among patient isolates and those of related carriers. In 70% of the families studied, all contact carriers had strains indistinguishable from that of the patient. In the other 30%, more than one meningococcal strain was recovered from the family. Sixty percent of the carrier isolates were recovered from adults. It was found that, among household contacts, the mother was most likely and the father was least likely to carry the disease isolate. Nonhousehold contacts were least likely to carry the disease isolate.
Defective parvoviruses acquired via the transplacental route protect mice against lethal adenovirus infection
Authors: Lipps B V , Mayor H D
Published: January 2020

Adeno-associated virus type 1 (AAV-1) interfered with the replication of its murine adenovirus (MAV) helper in primary mouse kidney cells and in 1-day-old ICR mice. Mice carrying AAV-1 acquired via the transplacental route were protected against lethal infection with MAV. The replication of AAV-1 in these mice could be triggered by multiple challenges with MAV, and antibodies to AAV-1 were subsequently detected.
Virus inoculation in mice bearing Ehrlich ascitic tumors: antigen production and tumor regression
Authors: Mettler N E , Clarke D H , Casals J
Published: January 2020

Ehrlich ascitic carcinoma, as developed in albino mice, has been used as a source of hemagglutinating and complement-fixing antigens, and it proved to be suitable for one type of antigen, or both, for at least 12 viruses of 16 tested. Hemagglutinins were obtained with members of arbovirus groups A, B, and C; complement-fixing antigens were obtained for at least one member of each antigenic group tested. Ehrlich ascitic tumor was compared with sarcoma 180 as a source of antigens; although sarcoma 180 showed many advantages over Ehrlich tumor, the latter gave, in general, better results for complement-fixing antigens. Oncolytic effect with complete recovery of the mice was observed in some instances. The highest recovery rate resulted with Congo and UNA viruses (40%), and the second highest rate resulted with dengue 2, St. Louis, Hazara, and Uukuniemi viruses (20%). The best survival was observed, in decreasing order, with Congo, St. Louis, dengue 2, Tacaribe, Sindbis, Junin, and Amapari viruses.
P-antigen-recognizing fimbriae from human uropathogenic Escherichia coli strains
Authors: Korhonen T K , Väisänen V , Saxén H , Hultberg H , Svenson S B
Published: January 2020

P-antigen-recognizing fimbriae (P fimbriae) from four pyelonephritogenic Escherichia coli strains and type 1 fimbriae from an E. coli strain and a Salmonella typhimurium strain were purified. The P fimbriae were morphologically similar to type 1 fimbriae. The purified P fimbriae agglutinated neuraminidase-treated human P1 and P2k erythrocytes but not p erythrocytes, which lack all P-blood group-specific glycosphingolipids. However, coating of neuraminidase-treated p erythrocytes with globoside rendered such erythrocytes agglutinable by the P fimbriae. The hemagglutinations were in all instances fully inhibited by the synthetic alpha-D-Galp-(1-4)-beta-D-Galp-1-O-Me glycoside. The binding specificity of the P fimbriae could also be demonstrated by using fimbriae coated onto latex particles and nontreated erythrocytes. It was thus concluded that the P fimbriae recognize and bind to the alpha-D-Galp-(1-4)-beta-D-Galp carbohydrate sequence occurring in the series of P-blood group antigen-specific glycosphingolipids. In contrast to both type 1 fimbriae, all four P fimbriae preparations showed multiple bands in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Antisera were raised in rabbits against the various E. coli fimbriae. In enzyme-linked immunosorbent assays each one of the antisera to the P fimbriae reacted to titers of log 4 to 7 with both the homologous and the heterologous P fimbriae, but not with the type 1 fimbriae of E. coli. In a reciprocal fashion, the antiserum to the type 1 fimbriae of one E. coli strain reacted only with the homologous type 1 but not with any of the P fimbriae preparations.
Effect of L18-MDP(Ala), a synthetic derivative of muramyl dipeptide, on nonspecific resistance of mice to microbial infections
Authors: Osada Y , Mitsuyama M , Une T , Matsumoto K , Otani T , Satoh M , Ogawa H , Nomoto K
Published: January 2020

By subcutaneous treatment with an aqueous solution of 6-O-stearoyl-N-acetylmuramyl-L-alanyl-D-isoglutamine [6-O-CH3-(CH2)16-CO-MurNAc-L-Ala-D-isoGln] [referred to here as L18-MDP(Ala)], an augmentation of the resistance of mice to Escherichia coli, Pseudomonas aeruginosa. Staphylococcus aureus, and Candida albicans infections was observed, but not to infections with Klebsiella pneumoniae and Listeria monocytogenes. Against E. coli infections, L18-MDP(Ala) was highly protective, irrespective of the administration route. Bacteremia occurring at an early phase of such infections was almost completely prevented by subcutaneous treatment 1 day before infection. Single or multiple doses were also effective against C. albicans infection. The phagocytosis of E. coli by mouse peritoneal polymorphonuclear cells was enhanced by treatment with the adjuvant, and the phagocytosis of K. pneumoniae was also enhanced, but only when the mice were treated either with rabbit normal serum or with a specific immune serum. The growth of the fungus in the kidneys was significantly inhibited, and growth was eliminated from the kidneys by treatment with the adjuvant once a day for 4 consecutive days, starting 1 day before infection. However, no growth suppression of L. monocytogenes in the livers or spleens of infected mice was observed when they were treated with a single dose of the adjuvant. This difference may be ascribed to the differences in the effector mechanisms of defense and to the different degree of augmentation of each defense mechanism by L18-MDP(Ala).
Dietary hepatic cholesterol elevation: effects on coxsackievirus B infection and inflammation
Authors: Campbell A E , Loria R M , Madge G E , Kaplan A M
Published: January 2020

Mice made hypercholesterolemic (HC) by diet are highly susceptible to coxsackievirus (CV) B5, whereas normal adult animals remain resistant. In attempting to define those dietary-induced physiological changes which contribute to altered resistance, a strong association between accumulation of intrahepatic cholesterol and increased CV B5-induced mortality was demonstrated, with maximum susceptibility to CV coinciding with a 2.5-fold increase in the ratio of hepatic cholesterol to protein. This metabolic imbalance was associated with a lower clearance rate of CV from the blood and liver of C57BL/6 mice, although virus-specific neutralizing antibody production was unaltered. In addition to CV, HC mice were more susceptible to an intravenous inoculation of Listeria monocytogenes in comparison to controls. The macrophage stimulant Corynebacterium parvum failed to increase resistance of HC mice to a high dose of CV B4 and L. monocytogenes and failed to induce the hepatomegaly, splenomegaly, and cellular infiltrate seen in the liver and spleen of normal animals. Furthermore, the peritoneal monocytic infiltrate induced by thioglycolate in normal animals was absent in HC mice. Results from these experiments suggest that decreased resistance to CV in the HC host is attributed to a defect in the nonspecific immune responses of macrophages and monocytes which are of primary importance in resistance to this virus and other infectious agents.
Respiratory syncytial virus infection in cyclophosphamide-treated cotton rats
Authors: Johnson R A , Prince G A , Suffin S C , Horswood R L , Chanock R M
Published: January 2020

Cotton rats infected intranasally with respiratory syncytial virus and immunosuppressed with cyclophosphamide shed virus for at least 7 weeks. Dissemination of virus beyond the respiratory tract was observed. In contrast, virus was recovered from infected, non-immunosuppressed rats for only 1 week, and only from the respiratory tract.
Herpes simplex virus-specific serum immunoglobulin a: detection in patients with primary or recurrent herpes infections and in healthy adults
Authors: Friedman M G , Kimmel N
Published: January 2020

A sensitive radioimmunoassay was used to determine levels of herpes simplex virus (HSV)-specific immunoglobulin A (IgA) in serial serum samples drawn from patients with primary HSV infections and from persons with recurrent HSV infections, and in single samples from 90 healthy adults. Significantly rising HSV IgA titers were detected in patients with primary infections, whereas those with recurrent infections had nonfluctuating titers. Sera of IgG-seropositive healthy adults were all positive for HSV-specific IgA without special pretreatment.
Nonspecific resistance to infection expressed within the Peyer's patches of the small intestine
Authors: MacDonald T T , Bashore M , Carter P B
Published: January 2020

Intraperitoneal or intraduodenal pretreatment of mice with dead Corynebacterium parvum failed to produce significant nonspecific resistance to Salmonella enteritidis infection in the Peyer's patches of the small intestine. However, mice pretreated with a single oral infection of live Listeria monocytogenes were capable of restricting the growth of S. enteritidis in the Peyer's patches. The ability of L. monocytogenes to induce nonspecific resistance was associated with the ability of this organism to cause an increase in the number of macrophages in the Peyer's patches.
Inhibition of herpes simplex virus multiplication by activated macrophages: a role for arginase?
Authors: Wildy P , Gell P G , Rhodes J , Newton A
Published: January 2020

Proteose-peptone-activated mouse macrophages can prevent productive infection by herpes simplex virus in neighboring cells in vitro whether or not those cells belong to the same animal species. The effect does not require contact between the macrophages and the infected cells, may be prevented by adding extra arginine to the medium, and may be reversed when extra arginine is added 24 h after the macrophages. Arginase activity was found both intracellularly and released from the macrophages. The extracellular enzyme is quite stable; 64% activity was found after 48 h of incubation at 37 degrees C in tissue culture medium. No evidence was found that the inefficiency of virus replication in macrophages was due to self-starvation by arginase. As might be predicted macrophages can, by the same mechanism, limit productive infection by vaccinia virus.
Stimulatory effect of N-acetyl Muramyl dipeptide in vivo: proliferation of bone marrow progenitor cells in mice
Authors: Wuest B , Wachsmuth E D
Published: January 2020

The effects of single and multiple injections of N-acetyl muramyl dipeptide (MDP) on peripheral leukocytes, colony-forming cells (i.e., bone marrow granulocyte-macrophage progenitor cells), and the humoral immune response (to bovine serum albumin) were investigated in mice. Whereas low doses of MDP (0.1 to 1 mg/kg) provoked lymphocytosis, larger doses (10 mg/kg upward) resulted in lymphocytopenia and an increase in the number of young stab neutrophils and monocytes. MDP induced a dose-dependent increase in the number of bone-marrow macrophage progenitor cells, the maximum being reached by a dose around 10 mg/kg. A 50% increase in the maximum effect was produced by a dose around 0.1 mg/kg. The higher the dose, the longer the increase in these progenitor cells persisted. MDP mediated a dose-dependent antibody response to small amounts of bovine serum albumin, correlating with the proliferation of progenitor cells.
Growth inhibition of oral streptococci in saliva by anionic proteins from two caries-free individuals
Authors: Cowman R A , Baron S S , Fitzgerald R J , Danziger J L , Quintana J A
Published: January 2020

Mixed saliva from two caries-free individuals possessed antimicrobial activity toward Streptococcus mutans and S. sanguis. This inhibitory activity was attributed to the presence of a group of four anionic proteins each of which strongly inhibited the growth of the oral streptococci in a saliva protein-based medium but not in a medium containing amino acids as a nitrogen source. These proteins, with isoelectric points of 4.70, 4.90, 4.98, and 5.05, respectively, neither reacted with antisera to immunoglobulin A, G, or M nor appeared to be functionally related to a number of salivary peroxidases, lactoferrin, or lysozyme. On this basis, they may represent a previously unreported group of growth-inhibitory antimicrobial factors occurring in the saliva of some individuals.
Specificity of immunoglobulin E in coccidioidomycosis and correlation with disease involvement
Authors: Cox R A , Baker B S , Stevens D A
Published: January 2020

Serum immunoglobulin E (IgE) antibodies were quantitated in 26 patients with active pulmonary coccidioidomycosis, 59 patients with active disseminated disease, 12 patients in clinical remission, and 91 healthy subjects. Significant differences were obtained in IgE serum levels of patients with active disease versus healthy subjects (P less than 0.0001). Patients with pulmonary coccidioidomycosis did not differ in their IgE levels when compared with patients with disseminated disease. However, serum IgE levels were significantly increased in patients with disease involving two or more organ systems when compared with patients with pulmonary disease or extrapulmonary disease involving a single organ system (P less than 0.02). Total serum IgE correlated with anti-Coccidioides IgE (P less than 0.001), but with only six exceptions, patients with anti-Coccidioides IgE also exhibited IgE antibodies to 1 or more of 12 common allergens. The correlation between hyperproduction of IgE and disease severity coupled with the depressed cell-mediated immune status of patients with this disease suggests a defect(s) in the T-lymphocyte population which functions to regulate IgE synthesis.
Selection of nonmucoid derivatives of mucoid Pseudomonas aeruginosa is strongly influenced by the level of iron in the culture medium
Authors: Boyce J R , Miller R V
Published: January 2020

We investigated the effects of cations on the stability in culture of mucoid strains pf Pseudomonas aeruginosa isolated from patients with cystic fibrosis by studying their effects on the selection of nonmucoid derivatives which arise by spontaneous mutation in cultures of mucoid organisms. Calcium ion concentrations in the range 0.55 to 1.85 mM had no effect on the growth or stability of the mucoid cultures. Higher levels (5.0 mM) inhibited the growth of both mucoid and nonmucoid cells. Likewise, magnesium ion in concentrations of 0.3 to 3.0 mM had no effect. The concentration of iron (either Fe2+ or Fe3+) had a profound effect on the selection of nonmucoid mutants in unshaken cultures of mucoid organisms. In medium containing 0.01 mM iron, nonmucoid mutants rapidly accumulated to a greater than 100-fold-higher frequency than the mucoid forms. Rates of accumulation of nonmucoid derivatives were lower in media containing lower concentrations of iron. The possible role of iron in the selection of nonmucoid cells from a population of mucoid P. aeruginosa is discussed.
Host plasma proteins on the surface of pathogenic Trichomonas vaginalis
Authors: Peterson K M , Alderete J F
Published: January 2020

Sodium dodecyl sulfate-gel electrophoresis and fluorography and fluorography technology revealed that pathogenic Trichomonas vaginalis was able to acquire numerous loosely associated plasma proteins during incubation in normal human plasma. These proteins were readily removed by repeated washing of the parasite in phosphate-buffered saline. Plasma proteins avidly bound to the surface of T. vaginalis were also detected using a highly sensitive and specific agglutination assay with protein A-bearing Staphylococcus aureus pretreated with monospecific antiserum directed against individual human serum proteins. These avidly associated plasma proteins could not be removed by repeated washing in phosphate-buffered saline or by treatment of washed, live organisms with surface-modifying reagents such as trypsin and periodate. A combined radioimmunoprecipitation-gel electrophoresis-fluorography methodology indicated that parasite biosynthesis of hostlike macromolecules was not responsible for the observed agglutination and reinforced the idea of trichosomal acquisition of plasma components. Finally, incubation of trichomonads with plasma in various buffers at different pH values did not alter the agglutination patterns. These and other data suggest that specific membrane sites trichomonal binding of host proteins. The biological significance of our results is discussed.
Reactivation of Rickettsia rickettsii in Dermacentor andersoni ticks: an ultrastructural analysis
Authors: Hayes S F , Burgdorfer W
Published: January 2020

Virulent Rickettsia in Dermacentor andersoni lose their pathogenicity and virulence for guinea pigs when subjected to physiological stresses, such as starvation (overwintering), of its tick vector. However, incubation of infected ticks at an elevated temperature (37 degrees C) for 24 to 48 h or feeding for a time (usually greater than 10 h) induces R. rickettsii to revert to a virulent state, a phenomenon defined as "reactivation." Electron microscopy reveals that the microcapsular and slime layers of R. rickettsii undergo changes dependent upon the physiological conditions within the tick vector. In engorged ticks, the microcapsular layer is readily identified as a discrete layer, approximately 16 nm thick, composed of globular subunits that have a periodicity of approximately 10 nm. The slime layer external to the microcapsular layer forms a discrete electron-lucent zone around the rickettsia. In starved ticks, neither the microcapsular layer nor slime layer remains a discrete entity. Instead, they are shed and form stringy, shredded, and somewhat flocculent strands of low electron density without periodicity. Incubation at 37 degrees C or feeding of starved infected ticks results in the restoration of a discrete microcapsular and slime layer. These reversible structural modifications are linked to physiological changes in the tick host and correlate with reactivation, i.e., restoration of pathogenicity and virulence of R. rickettsii.
Direct activation of the J774.1 Murine macrophage cell line by mycoplasma arthritidis
Authors: Dietz J N , Cole B C
Published: January 2020

Viable Mycoplasma arthritidis and supernatants from M. arthriditis cultures produced marked morphological changes in the J774.1 continuous macrophage line similar to those seen during activation of these cells by Mycobacterium bovis BCG cell walls. The mycoplasma-treated macrophages developed pronounced tumoricidal activity against syngenic 3T12-3 target cells and developed an enhanced capacity for the killing of intracellular listeriae, including both virulent and laboratory-maintained strains. Increased acid phosphatase levels and [14C]glucosamine uptake were also seen. We conclude that mycoplasmas can profoundly alter the functions of macrophages, an event which may not only have in vivo significance with regard to disease pathogenesis, but which may pose considerable problems for in vitro work when unsuspected mycoplasma contamination is present.
Comparison of virulence and colonizing capacity of Escherichia coli K1 and non-K1 strains in neonatal rats
Authors: Scannapieco F A , Guerina N G , Goldmann D A
Published: January 2020

Neonatal rats fed three strains of Escherichia coli K1 at birth had bacteremia rates of 29 to 81%; negligible bacteremia was seen with K92 and an unencapsulated strain. Despite this marked difference in virulence, K1, K92, and the unencapsulated strain all promptly, reliably, and stably colonized the entire alimentary tract, from pharynx to colon.
Infection of marmosets with parainfluenza virus types 1 and 3
Authors: Hawthorne J D , Lorenz D , Albrecht P
Published: January 2020

Infection of wild marmosets (Saguinus mystax) with strains of parainfluenza virus types 1 and 3 resulted in acute respiratory infection. Virus replication in the upper respiratory tract was of a degree similar to that seen in children acutely infected with parainfluenza viruses. Serum antibody developed with both virus types; however, local secretory antibody was not detectable. The infection was transmissible to susceptible animals up to 3 days inoculation of the primary animal.
Glyoxylate metabolism and adaptation of Mycobacterium tuberculosis to survival under anaerobic conditions
Authors: Wayne L G , Lin K Y
Published: January 2020

Tuberculosis is characterized by periods in which the disease may be quiescent or even clinically inapparent, but in which tubercle bacilli persist and retain the potential to reactivate the disease. The present study was carried out in pursuit of an in vitro model which might contribute to the understanding of the physiology of nonreplicating persisters, with oxygen limitation used as the means of inducing this state. When actively growing aerated cultures of Mycobacterium tuberculosis were suddenly placed under anaerobic conditions the bacilli died rapidly, with a half-life of 10 h. When the bacilli were grown in liquid medium without agitation, they adapted to the microaerophilic conditions encountered in the sediment; the adapted bacilli in the sediment did not replicate there but were tolerant of anaerobiosis, exhibiting a half-life of 116 h. Among the early events associated with the adaptation were the synthesis of an antigen designated URB, the function of which is not known, and a fourfold increase in isocitrate lyase activity. The bacilli later exhibited a 10-fold increase in synthesis of a glycine dehydrogenase that catalyzes the reductive amination of glyoxylate, concomitantly oxidizing NADH to NAD. Specific activities of other enzymes studied were either not affected or moderately diminished in the sedimented bacilli. It is proposed that the glyoxylate synthesis in this model serves mainly to provide a substrate for the regeneration of NAD that may be required for the orderly completion of the final cycle of bacillary replication before oxygen limitation stops growth completely. This orderly shutdown is essential to continued survival of M. tuberculosis in a quiescent form.
Resistance to infections in mice with defects in the activities of mononuclear phagocytes and natural killer cells: effects of immunomodulators in beige mice and 89Sr-treated mice
Authors: Morahan P S , Coleman P H , Morse S S , Volkman A
Published: January 2020

Beige mice, which are a homolog of the Chediak-Higashi syndrome, and mice treated with 89Sr to destroy the bone marrow provide animal models of defects in mononuclear phagocyte and natural killer cell functions. The innate resistance of these mice to viruses such as herpes simplex and encephalomyocarditis viruses, however, is normal. Moreover, treatment of the mice with immunomodulators such as Propionibacterium acnes (formerly designated Corynebacterium parvum) and pyran produced a significant increase in resistance to encephalomyocarditis virus. The antiviral effect of P. acnes in 89Sr-treated mice was exhibited during marked monocytopenia and without evidence for an inflammatory influx of macrophages into the peritoneal cavity. Treatment with P. acnes was also effective in increasing the resistance of beige mice to infection with Listeria monocytogenes. Thus, immunomodulators can be effective in mice that exhibit impaired macrophage and natural killer cell functions.
Protection against lethal challenge of BALB/c mice by passive transfer of monoclonal antibodies to five glycoproteins of herpes simplex virus type 2
Authors: Balachandran N , Bacchetti S , Rawls W E
Published: January 2020

Monoclonal antibodies secreted by six hybridomas and recognizing antigenic sites on glycoproteins gC, gAB, gD, gE, and gF of herpes simplex virus type 2 were examined for their ability to protect BALB/c mice from lethal infection by the virus. Administration of monoclonal antibodies to individual glycoproteins intraperitoneally 3 h before footpad challenge with 10 times the 50% lethal dose of virus protected between 35 and 75% of the mice, except for one of two monoclonal antibodies recognizing antigens on gC. The antibodies did not neutralize virus in vitro and protected A/J mice deficient in the fifth component of complement as efficiently as complement-sufficient BALB/c mice. A good correlation was found between protection and titers of monoclonal antibodies assessed by antibody-dependent cell-mediated cytolysis. The results indicate that any of the glycoproteins can serve as antigens for a protective immune response. In addition, the data are compatible with protection being mediated by an antibody-dependent cell-mediated cytolysis mechanism.
Purification of a Protective Antigen from a Saline Extract of
Pasteurella multocida
Authors: Syuto Bunei , Matsumoto Masakazu
Published: January 2020

It has been shown previously that soluble material extracted from
Pasteurella multocida
P-1059 by a 2.5% NaCl solution protects turkeys from generalized septicemia at a subsequent challenge exposure to the organism. In the present study, a protective antigen was purified from the crude soluble material by chromatographic methods. Four protein peaks were obtained by gel filtration with Sephadex G-200. The protective antigen was detected only in the first peak fraction, which contained a substantial amount of carbohydrate. The peak 1 fraction was adsorbed onto DEAE-cellulose and eluted by a linear gradient of NaCl. Fractions corresponding to a single protein peak were pooled and passed through an immunoadsorbent column to remove any possible serum component originating from the growth medium. The purified antigen had a carbohydrate/protein ratio of 1.5 and formed a single precipitin line with rabbit antiserum against the crude material in gel diffusion and immunoelectrophoresis analyses. The antigen produced antibodies in rabbits and turkeys which formed a single precipitin line against the crude material. Upon sodium dodecyl sulfate-polyacryl-amide gel electrophoresis, the purified antigen showed three protein bands, corresponding to molecular weights of 44,000, 31,000, and 25,000, and one carbohydrate band. The carbohydrate band did not correspond to any of the three protein bands. Upon isoelectric focusing gel analysis, the purified antigen showed two bands (pI = 3.5 to 4.0 and 4.5 to 5.5), but the two bands were antigenically identical by isoelectric focusing crossed immunoelectrophoresis. The 50% protective dose of the purified antigen was between 10 and 50 μg of protein in trials where two doses were given at 14-day intervals to 10- to 20-week-old turkeys.