bluuebunny/crossref_metadata_2025 huggingface dataset:
Murine malaria: genetic control of resistance to Plasmodium chabaudi
Authors: Stevenson M M , Lyanga J J , Skamene E
Published: January 2020

Strain variation in the level of resistance to malaria was investigated in inbred strains of mice after infection with Plasmodium chabaudi. When infected intraperitoneally with 10(6) P. chabaudi-parasitized erythrocytes, mice of 11 inbred strains could be separated into two groups by using survival time as the criterion; C57BL/6J, C57L/J, DBA/2J, CBA/J, and B10.A/SgSn mice were found to be resistant to P. chabaudi, whereas A/J, DBA/1J, BALB/c, C3H/HeJ, AKR/J, and SJL/J mice were susceptible. An examination of F1 hybrids revealed that resistance was dominant over susceptibility. A segregation analysis of backcross and F2 progeny derived from susceptible A/J and resistant B10.A/SgSn parental mice suggested that host resistance in this strain combination was genetically controlled by a single, dominant, non-H-2-linked gene. Inheritance of resistance was autosomal, but expression of the trait was influenced by the sex of the host, female mice being more resistant than male mice. Phenotypic expression of the resistance gene was apparent within 6 days of infection as a significant difference between resistant and susceptible mice in the level of parasitemia. A preliminary analysis of the mechanism of resistance showed that compared with susceptible A/J mice, resistant B10.A/SgSn hosts had an augmented erythropoietic response during the course of malaria, as well as phenylhydrazine-induced anemia. These results suggest that the ability to replace destroyed erythrocytes quickly and efficiently may determine host survival after infection with P. chabaudi.
In vitro studies on the adjuvanticity of Brucella fractions
Authors: Serre A , Vendrell J P , Huguet M F , Cannat A
Published: January 2020

Two Brucella fractions, the murein-linked fraction PI and the murein-free fraction SF, behave as in vitro adjuvants for primary anti-sheep erythrocyte responses: added to Mishell and Dutton-type cultures of spleen cells from B6/DB F1 mice they significantly enhance the number of direct anti-sheep erythrocyte PFC observed on day 5. They exert both nonspecific, polyclonal activating effects and antigen-dependent specific adjuvanticity. These two functions, however, differ in their dose responses and in their cellular requirements and can therefore be dissociated. Thus, polyclonal activation requires high doses of the "adjuvant fraction," is enhanced by adherent-cell depletion, and is not impaired by T-cell depletion. Specific adjuvanticity, on the other hand, requires lower doses of the adjuvant fractions (very high doses are in fact suppressive) and is T-cell and adherent-cell dependent. Moreover, adjuvanticity can be transferred to unstimulated spleen cells (or restored in adherent-cell-depleted populations) by PI- or SF-stimulated adherent cells or by the filtered supernatants of such cultures; adjuvant-soluble factors are therefore involved in the phenomena of adherent, T- and B-cell cooperation required for the adjuvanticity of Brucella fractions.
High-level induction of gamma interferon with various mitogens in mice pretreated with Propionibacterium acnes
Authors: Okamura H , Kawaguchi K , Shoji K , Kawade Y
Published: January 2020

Various T-cell mitogens induced high levels of circulating gamma interferon (IFN-gamma) in mice that had been pretreated with Propionibacterium acnes. Administration of lipopolysaccharide, a B-cell mitogen, to these mice also caused pronounced production of IFN-gamma in addition to IFN-alpha and IFN-beta. The enhanced induction was most marked at about 1 week after the pretreatment.
Molecular heterogeneity of heat-labile enterotoxins from human and porcine enterotoxigenic Escherichia coli
Authors: Tsuji T , Taga S , Honda T , Takeda Y , Miwatani T
Published: January 2020

The heat-labile enterotoxins produced by human enterotoxigenic Escherichia coli (LTh) and porcine enterotoxigenic E. coli (LTp) were purified to homogeneity, and their molecular properties were compared with those of purified cholera enterotoxin (CT). On polyacrylamide gel disk electrophoresis without sodium dodecyl sulfate, LTh, LTp, and CT differed in mobility, suggesting differences in their ionic charges. The pI values of LTh, LTp, and CT were 7.50, 8.10, and 6.80, respectively. On sodium dodecyl sulfate-polyacrylamide gel slab electrophoresis, the B subunit and A1 and A2 fragments of LTh, LTp, and CT differed in mobility, suggesting that they differed in molecular size. Their molecular sizes seemed to decrease in the following order: B subunit, LTh greater than LTp congruent to CT; A1 fragment, LTp greater than LTh congruent to CT; A2 fragment, LTh congruent to CT greater than LTp. Amino acid compositions of LTh, LTp, and CT were also compared.
Relationship between the mouse colonizing ability of a human fecal Escherichia coli strain and its ability to bind a specific mouse colonic mucous gel protein
Authors: Cohen P S , Rossoll R , Cabelli V J , Yang S L , Laux D C
Published: January 2020

Escherichia coli F-18, isolated from the feces of a healthy human, is an excellent colonizer of the large intestines of streptomycin-treated CD-1 mice. E. coli F-18 Col-, a poor mouse colonizer relative to F-18, lacks a 3 X 10(7)-dalton plasmid present in E. coli F-18. Both strains are human type A erythrocyte hemagglutination negative, have identical surface hydrophobicities, contain the same number of lipopolysaccharide molecules with the same O-side chain length, and have identical amounts of capsule. Differences between the two strains were observed. The relative amounts of specific outer membrane proteins differed, and E. coli F-18 was less motile than E. coli F-18 Col-. The abilities of the two strains to bind mouse large intestine mucous gel was also examined. Although each strain was able to use mucous gel as the sole source of carbon and nitrogen with equal ability, E. coli F-18 bound between two and three times more mucous gel than did E. coli F-18 Col-. Most of the difference in mucous gel binding ability of the two strains was accounted for by the greater ability of E. coli F-18 lipopolysaccharide to bind a single 26,000-dalton mucous gel protein. E. coli J5-3, a typical K-12 strain that is also a poor colonizer relative to E. coli F-18, was identical to E. coli F-18 Col- with respect to mucous gel binding ability.
Genetic transformation of putative cariogenic properties in Streptococcus mutans
Authors: Perry D , Wondrack L M , Kuramitsu H K
Published: January 2020

Rough colonial morphology and bacteriocin production, two properties which may be associated with the cariogenicity of Streptococcus mutans, were transformed into several strain GS-5 mutants defective in each respective property. Transformation was determined by observing the frequency of cotransfer of these properties with different reference markers. The rough colonial transformants were identical to the parental GS-5 strain with respect to ability to synthesize water-insoluble glucans and undergo in vitro sucrose-dependent colonization of glass surfaces. Alterations in the growth medium and the concentration of the initial cell inoculum resulted in an approximate 10-fold increase in the frequency of transformation of strain GS-5 compared to previous observations.
Immunobiological activities of synthetic lipid A analogs and related compounds as compared with those of bacterial lipopolysaccharide, re-glycolipid, lipid A, and muramyl dipeptide
Authors: Kotani S , Takada H , Tsujimoto M , Ogawa T , Mori Y , Sakuta M , Kawasaki A , Inage M , Kusumoto S , Shiba T , Kasai N
Published: January 2020

Thirteen acylated and phosphorylated derivatives of beta-1,6-linked glucosamine disaccharide (lipid A analogs), which were synthesized after the structural model of Salmonella-type lipid A, and seven similar derivatives of glucosamine monosaccharide (lipid A-related compounds) were studied for their immunobiological activities. These included mitogenicity and polyclonal B cell activation enhancement of migration of monocytes and polymorphonuclear leukocytes derived from human peripheral blood, stimulation of guinea pig peritoneal macrophages, activation of human complement, and stimulation of serum antibody production and induction of delayed-type hypersensitivity against ovalbumin in guinea pigs. Comparisons were made with lipid A, RE-glycolipid, lipopolysaccharide of natural sources, and a well-known synthetic adjuvant, N-acetylmuramyl-L-alanyl-D-isoglutamine. Some of the lipid A analogs were found to manifest the mitogenic, polyclonal B cell-activating macrophage-stimulating, complement-activating, and immunostimulating activities, although the observed activities were generally far less than those of natural products in intensity and efficiency. Other immunobiological effects exhibited by most of the synthetic lipid A analogs were the enhancement of migration of monocytes and polymorphonuclear leukocytes. It is premature to draw definite conclusions on structure-activity relationships, since a few compounds which were active in some assay systems were scarcely active in other assays. However, an indisputable fact was that beta-1,6-glucosamine disaccharide 1 alpha,4'-diphosphate, which carries two amide-bound (R)-3-hydroxytetradecanoyl and three ester-bound tetradecanoyl residues, and thus has the structure most closely resembling natural lipid A among test compounds in this study, was definitely active in all of the present assay systems. However, its potency was generally much less than natural products. Some of glucosamine monosaccharide derivatives, especially N-(R)-3-[(R)-3-hydroxytetradecanoyloxy]tetradecanoyl glucosamine, also exerted all of the in vitro activities described above. This fact suggests that a glucosamine disaccharide structure may not necessarily be a prerequisite as far as the in vitro immunobiological activities tested are concerned.
Lyme disease spirochetes and ixodid tick spirochetes share a common surface antigenic determinant defined by a monoclonal antibody
Authors: Barbour A G , Tessier S L , Todd W J
Published: January 2020

Ixodid tick-associated spirochetes have been implicated as the etiological agents of Lyme disease. We raised a murine monoclonal antibody (H5332) against a spirochete, strain B31, isolated from Ixodes dammini ticks. In indirect immunofluorescence assays and western blot analyses, H5332 reacted with whole cells or isolated components of not only strain B31 but also spirochetes isolated from Ixodes ricinus ticks, a field mouse, a raccoon, and patients with Lyme disease. In contrast, H5332 did not bind to representative borreliae, treponemes, and leptospires. Using indirect immunofluorescence assays and immune electron microscopy, we found the H5332 determinant to be diffusely distributed over the surface of prefixed spirochetes but to be aggregated in patches when the organisms were incubated with H5332 and a second ligand before fixation. Radioimmunoprecipitation and western blot studies revealed the H5332 determinant to be either on or tightly associated with an abundant outer membrane protein with an apparent subunit molecular weight of 31,000.
Development and characterization of monoclonal antibodies to Marek's disease tumor-associated surface antigen
Authors: Liu X F , Lee L F
Published: January 2020

Four monoclonal antibodies, A35, B94, EB29, and G152, against Marek's disease tumor-associated surface antigen have been developed and their specificities studied against a panel of Marek's disease and lymphoid leukosis primary tumors; Marek's disease, and lymphoid leukosis, and reticuloendotheliosis lymphoblastoid cell lines; and normal chicken cells. A35 and G152 are of the immunoglobulin M class, and B94 and EB29 are of the immunoglobulin G1 subclass.
Replication at body temperature selects a neurovirulent herpes simplex virus type 2
Authors: Thompson R L , Stevens J G
Published: January 2020

A prototype strain of herpes simplex virus type 2 (HG-52) replicated at 31 degrees C was avirulent when inoculated intracranially into mice. This property was not altered after serial passage of the agent at 31 degrees C, but the virus became virulent after passage at 37.5 degrees C. The selection was not merely for an agent which replicated more efficiently at the higher temperature, but for viruses with enhanced capacity to replicate in the brains of mice. Virulent descendants of plaque-purified avirulent stocks were obtained in each instance attempted.
Effect of antithymocyte serum on the course of chlamydial genital infection in female guinea pigs
Authors: Rank R G , Barron A L
Published: January 2020

The treatment of female guinea pigs, infected in the genital tract with the chlamydial agent of guinea pig inclusion conjunctivitis, with rabbit anti-guinea pig thymocyte serum extended the course of the infection by 20 to 30 days. The rabbit anti-guinea pig thymocyte serum was shown to suppress delayed hypersensitivity responses to the guinea pig inclusion conjunctivitis agent and the contact allergen oxazolone. The appearance of antibody in genital secretions was delayed, but the infection persisted at low levels even when normal serum and secretory antibody titers were attained, indicating that cell-mediated immunity may play a role in the resolution of chlamydial genital infections.
Toxicity but not arthritogenicity of Mycoplasma arthritidis for mice associates with the haplotype expressed at the major histocompatibility complex
Authors: Cole B C , Thorpe R N , Hassell L A , Washburn L R , Ward J R
Published: January 2020

The use of inbred and congenic mouse strains established that toxicity and death induced by Mycoplasma arthritidis associates with the haplotype expressed at the murine major histocompatibility complex. Mice bearing H-2k and H-2d are susceptible, whereas those bearing H-2b are much more resistant. Mice susceptible to toxicity exhibited massive peritoneal adhesions and a decreased ability to clear organisms from the peripheral circulation. However, the severity of acute arthritis developing over a 3-month period was not statistically related to the haplotype expressed at the major histocompatibility complex. Lymphocyte activation in vitro by a soluble T-cell mitogen is also dependent on a similar haplotype expression.
Nonspecific induction of immunoglobulin M antibodies to periodontal disease-associated microorganisms after polyclonal human B-lymphocyte activation by Fusobacterium nucleatum
Authors: Mangan D F , Won T , Lopatin D E
Published: January 2020

The production of antibodies to oral bacteria was determined in lymphocyte cultures stimulated with sonicated Fusobacterium nucleatum, a potent inducer of polyclonal B-cell activation. After 9 days the cultures were examined by a microenzyme-linked immunosorbent assay for immunoglobulin M (IgM) antibodies to F. nucleatum, Bacteroides gingivalis, Actinomyces viscosus, and Streptococcus sanguis. Antibodies to these four bacteria were detected in cultures stimulated with polyclonal B-cell activation-inducing concentrations of F. nucleatum. However, significant concentrations of antibodies to F. nucleatum, but not to the other three microorganisms, were produced in cultures that received suboptimal polyclonal B-cell activation-inducing doses of F. nucleatum. Absorption studies indicated the specificity of the antibodies to each of the bacteria tested. IgM antibody production induced by F. nucleatum was enhanced by the addition of T cells. The production of IgM antibodies to the bacteria was reproducible in cultures from a single person tested on 3 consecutive days. The concentration of antibodies in replicate cultures, however, fluctuated greatly. To obtain consistent responses on successive days, multiple replicate cultures were required. These results suggest that F. nucleatum, which is frequently present in subgingival plaque, could induce the production of antibodies not only to F. nucleatum, but also to other microorganisms associated with periodontal diseases.
Analysis of the bimodal chemiluminescence pattern stimulated in human neutrophils by chemotactic factors
Authors: Bender J G , Van Epps D E
Published: January 2020

Chemotactic factors, which are important in attracting neutrophils to inflammatory sites, have also been shown to stimulate oxidative metabolism, resulting in increased chemiluminescence and release of superoxide anion (O2-). We observed a unique bimodal chemiluminescence pattern upon stimulation with either the complement-derived factor C5a or formyl-methionyl-leucyl-phenylalanine. A sharp peak of activity occurred within 1 to 2 min, and a second more extended peak was seen between 3 and 6 min. Enhancement of both peaks occurred when the cells were pretreated with cytochalasin B. Expression of both peaks was found to be related to cell density, and expression of the second peak was not dependent upon extracellular metabolites released during the first peak. Cells preincubated in luminol and then thoroughly washed responded with only a single peak coincident with the second peak. Together these findings indicate that the first peak is extracellular in origin, whereas the second peak is cell associated. Studies with scavengers of oxygen intermediates and inhibitors of myeloperoxidase for the oxidation of luminol, which may occur in part through the formation of HOCl as well as through a non-HOCl-mediated mechanism. Evidence for a non-HOCl-mediated mechanism comes from experiments in which luminol, myeloperoxidase, and O2- generated by xanthine-xanthine oxidase produce luminescence in the absence of chloride ion. These studies provide further insight into the sequence of events which occur during the stimulation of neutrophils with chemotactic factors and the nature of neutrophil chemiluminescence.
Induction of selective biological responses to chemoattractants in a human monocyte-like cell line
Authors: Kay G E , Lane B C , Snyderman R
Published: January 2020

The availability of monocyte cell lines that can be induced to differentiate in a predictable fashion can provide important tools for the study of the biochemical mechanisms of specific cellular responses. The U937 human monocyte cell line was previously shown to differentiate into chemotactically responsive cells when incubated with supernatants of lectin-stimulated lymphocytes (conditioned medium). Considering the heterogeneous nature of stimulated lymphocyte supernatants, attempts were made to identify well-defined agents that could reproducibly induce U937 cell differentiation. Both dimethyl sulfoxide and dibutyryl cAMP induced expression of receptors for the N-formylated oligopeptide chemoattractants in U937 cells. Unstimulated U937 cells contained no detectable receptors. After cells were exposed to 1 mM dibutyryl cAMP, 1.3% dimethyl sulfoxide, or 5% conditioned medium for 72 h, the average number of oligopeptide chemoattractant receptors per U937 cell was 33,000, 4,000, and 3,400, respectively. Specific binding proteins for the chemoattractants were identified by covalent affinity labeling on the differentiated U937 cells as well as on normal human monocytes. Cells exposed to conditioned medium responded chemotactically, secreted lysosomal enzymes, and formed superoxide anion when incubated with the chemoattractant. Treatment of U937 cells with dibutyryl cAMP resulted in the most reproducible and rapid increase in the number of chemoattractant receptors as well as in chemotactic responsiveness. The receptors on dibutyryl cAMP-treated cells and on dimethyl sulfoxide-treated cells initiated chemotaxis and lysosomal enzyme secretion in response to chemoattractants, but not the formation of superoxide anion. These findings demonstrate that development of the chemotactic and respiratory burst functions during the differentiation of a monocyte-like cell line can occur independently.
Opsonic activity of blister fluid from burn patients
Authors: Deitch E A
Published: January 2020

The combination of skin loss and immune depression after thermal injury predisposes burn patients to an increased risk of infection. Since the commonest site of infection in the burn patient is the burn wound itself, we elected to study the opsonic activity of locally produced blister fluid, from 18 thermally injured patients, for the two most common organisms colonizing the burn wound (Pseudomonas aeruginosa and Staphylococcus aureus). Blister fluid was as good an opsonin source for staphylococcus as normal serum. In contrast, the blister fluid did not support either the phagocytosis of the intracellular killing of P. aeruginosa. The poor opsonic activity of blister fluid for P. aeruginosa did not appear to be due to the presence of an inhibitory factor(s) since the addition of normal serum restored the opsonic activity of the blister fluid to normal. The concentrations of immunoglobulins and the complement components C3 and C4 in the blister fluid samples were less than half the level of those in normal serum. The opsonic activity of the blister fluid could not be restored to normal by the addition of either immunoglobulin or heat-inactivated serum (56 degrees C for 30 min). Thus, the opsonic factor(s) missing from the blister fluid was heat labile and thus probably represents complement components. That blister fluid had impaired opsonic activity for P. aeruginosa but not for S. aureus indicated that a local humoral defect may be responsible, at least in part, for the high incidence of gram-negative organisms, especially pseudomonads, colonizing the burn wound after thermal injury.
Antibody-independent immunity to reinfection malaria in B-cell-deficient mice
Authors: Grun J L , Weidanz W P
Published: January 2020

Immunity to "reinfection malaria" or "premunition" was studied in B-cell-deficient mice which had previously experienced acute malaria caused by the avirulent plasmodia Plasmodium yoelii or P. chabaudi or by the lethal P. vinckei. Such mice resisted challenge infection with large numbers of homologous parasites but differed in their capacity to resist challenge with heterologous species. Mice immune to P. yoelii resisted infection with P. chabaudi but developed acute-type, albeit nonlethal, infections when challenged with P. vinckei. Whereas mice immune to P. chabaudi resisted challenge with P. vinckei and vice versa, they developed fulminating malaria and died when infected with P. yoelii. The data suggest that immunity to reinfection malaria in B-cell-deficient mice, although antibody independent, is mediated by different mechanisms of resistance depending upon the plasmodial species used to initiate acute infection. Additional evidence supporting this concept was gained from preliminary experiments in which immunity to reinfection was measured by the ability of chronically infected mice to control endogenous parasites at low levels. B-cell-deficient mouse strains showed genotypic differences in their ability to develop immunity to reinfection with P. yoelii. In contrast, the same mouse strains uniformly developed immunity to reinfection with P. chabaudi. These findings suggest that different genetic loci control resistance to reinfection malaria caused by different species of plasmodia. Finally, B-cell-deficient mice acutely infected with lethal plasmodia, P. vinckei or P. berghei, died at the same time or earlier than similarly infected immunologically intact mice, indicating that "early death" in virulent malarial infections is an antibody-independent phenomenon.
Inhibition of human polymorphonuclear leukocyte respiratory burst, bactericidal activity, and migration by pneumolysin
Authors: Paton J C , Ferrante A
Published: January 2020

The in vitro effects of pneumolysin, a sulfhydryl-activated toxin produced by Streptococcus pneumoniae, on various functions of human polymorphonuclear leukocytes (PMNLs) was investigated. Treatment of PMNLs with highly purified toxin significantly inhibited respiratory burst (in response to stimulation), ability to kill opsonized pneumococci, chemotaxis, and random migration. These inhibitions were observed at very low toxin doses (less than or equal to 1 hemolytic unit (2 ng) per 10(6) PMNLs), which had no effect on PMNL viability. These results suggest that pneumolysin could function in pathogenicity by interfering with the ability of PMNLs to migrate toward and kill pneumococci.
Colonial opacity variation in Mycoplasma pulmonis
Authors: Liss A , Heiland R A
Published: January 2020

Colonial size and opacity variation were observed in four independently isolated strains of the murine pathogen Mycoplasma pulmonis. Selecting colonial opacity variants of similar size, we identified opaque and transparent stable variants. Opaque colony-derived broth cultures shed transparent colonies at a rate of about 1.2 X 10(-8) per CFU per generation. The reverse conversion was about two orders of magnitude less frequent. Appearance of opacity and plating efficiency of each pure culture were altered by changing the serum source used to supplement the growth medium. Horse or sheep serum was most efficient at accentuating visualization of opacity differences. Fetal bovine serum was least efficient. In two M. pulmonis strains, each opacity variant showed a distinctive polypeptide profile, as displayed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In the same strains, distinctive intrastrain differences were found by agarose gel electrophoresis to display the DNA fragments produced after digestion by several endonucleases. Each pure culture variant retained these differences in DNA even when grown in a medium supplemented with a serum which did not accentuate visualization of the opacity phenotype. Characterization of variants in 30 other M. pulmonis strains is in progress.
Postphagocytic detection of glycopeptidolipids associated with the superficial L1 layer of Mycobacterium intracellulare
Authors: Tereletsky M J , Barrow W W
Published: January 2020

The superficial L1 layer of Mycobacterium intracellulare serovar 20 was detected by immunocytochemical procedures based on C-mycoside glycopeptidolipid (GPL) antigens. Specific immune serum was produced by injecting a GPL-methylated bovine serum albumin complex into rabbits with Freund incomplete adjuvant. The resulting antibodies were used to label serovar 20 with goat anti-rabbit immunoglobulin G (IgG) conjugated with either fluorescein or ferritin. The labeled GPL antigens were then detected by fluorescent and electron microscopy. With these procedures, it was possible to observe the superficial distribution of the GPL antigens on serovar 20 and to confirm their intraphagosomal location within the macrophages after phagocytosis. These immunocytochemical procedures now make it possible to monitor these mycobacterial antigens during phagocytosis and may be helpful in determining their role in pathogenesis.
Murine peritoneal macrophages support murine cytomegalovirus replication
Authors: Shanley J D , Pesanti E L
Published: January 2020

Because there have been different conclusions regarding the susceptibility of murine macrophages to murine cytomegalovirus (MCMV) infection and replication, we have undertaken a detailed comparison of MCMV infection of macrophages with that of a permissive cell line, mouse embryo cells. Although both cell lines undergo productive infections with MCMV, there are marked differences in certain aspects of the viral replication which may account for some of the different conclusions regarding the MCMV cycle in macrophages. Although both cell lines produce MCMV after infection, the time course of the infection differed markedly between the cell types. Similarly, the proportion of infected macrophages that are releasing infection virions is much smaller than the proportion of a comparably infected mouse embryo cell culture. Tissue culture passage of MCMV first enhanced (after one passage) and then reduced the infectivity of the virus for macrophages in vitro. The delayed time course and lesser production at early intervals after infection of macrophage cultures could not be attributed to demonstrable inhibitors or to replication in contaminating fibroblasts in the macrophage cultures.
Comparison of primary skunk brain and kidney and raccoon kidney cells with established cell lines for isolation and propagation of street rabies virus
Authors: Umoh J U , Blenden D C
Published: January 2020

Cell cultures prepared from skunk kidney, raccoon kidney, and skunk brain were compared with CER, murine neuroblastoma (C1300, clone NA), baby hamster kidney (BHK-21, S-13), and dog kidney (MDCK) cell lines for virus isolation and propagation of street and fixed rabies virus. The skunk brain cells were suitable for efficient replication of all the virus isolates. They were comparable to CER and murine neuroblastoma cells for virus isolation and propagation. None of the other cell cultures was satisfactory. Further work is under way to refine the skunk brain cell cultures.
Induction of oral tolerance in mice unresponsive to bacterial lipopolysaccharide
Authors: Saklayen M G , Pesce A J , Pollak V E , Michael J G
Published: January 2020

C3H/HeJ lipopolysaccharide (LPS)-unresponsive and closely related C3H/HeSn LPS-responsive mice were rendered tolerant to hen albumin by antigen feeding before parenteral immunization. Both single and multiple feedings of antigen were effective in inducing tolerance to hen albumin in LPS-responsive and -unresponsive strains of mice. Our data demonstrate that ability to respond to LPS is not a prerequisite for induction of oral tolerance to a soluble protein antigen.
Age-related loss of Lyt-1,2 cells in C58 mice results in susceptibility to lactic dehydrogenase virus-induced polioencephalomyelitis
Authors: Bentley D M , Watson S R , Morris R E
Published: January 2020

C58 mice (aged greater than or equal to 5 months) are susceptible to age-dependent polioencephalomyelitis, a paralytic central nervous system disease induced by lactic dehydrogenase virus. Susceptibility results from the loss of protective T cells. Data are presented showing a positive correlation between the age-related loss of Lyt-1,2 cells and the development of susceptibility to neuroparalytic lactic dehydrogenase virus infection.
Hemolysis determinant common to Escherichia coli strains of different O serotypes and origins
Authors: de la Cruz F , Zabala J C , Ortiz J M
Published: January 2020

Ten Escherichia coli hemolytic strains, isolated from various types of human infection and belonging to at least six different O serotypes were analyzed. In all these strains, our results are consistent with the hly genetic determinant being located on the bacterial chromosome. An hly-specific probe (plasmid pAN215) was used to detect homologous fragments in the strains analyzed by the Southern blotting technique. It was found that all 10 strains contain sequences that hybridize against the probe (greater than 85% homology) and thus contain hly genetic determinants very similar to those found on Hly plasmids. These results strongly suggest that there is a unique ubiquitous genetic determinant responsible for the hemolytic phenotype in E. coli.
Induction of endotoxin tolerance with nonpyrogenic O-antigenic oligosaccharide-protein conjugates
Authors: Lindberg A A , Greisman S E , Svenson S B
Published: January 2020

We prepared a dodecasaccharide, specific for the O-antigenic polysaccharide chain of Salmonella typhimurium (O-antigens 4 and 12), by the partial hydrolysis of the O-polysaccharide chain, utilizing bacteriophage 28B endo-alpha-L-rhamnosidase. The dodecasaccharide was shown by chemical and spectroscopical analyses to be totally devoid of lipid A and core oligosaccharide. By coupling this dodecasaccharide to human serum albumin, a glycoconjugate (DODECA-4809-ITC-HSA) was prepared and found to be (i) nonpyrogenic, (ii) unable to gelate a Limulus amoebocyte lysate, and (iii) unable to induce early-phase pyrogenic tolerance to endotoxin. Rabbits immunized either intravenously (with the glycoconjugate suspended in saline) or intrapopliteally (with the glycoconjugate suspended in Freund complete adjuvant) developed a significant although modest pyrogenic tolerance against challenge with the O-antigenic homologous S. typhimurium lipopolysaccharide (P less than 0.025 and P less than 0.01 for immunized and control rabbits, respectively). The evoked tolerance was O-antigen specific since no pyrogenic tolerance against challenge with lipopolysaccharide from S. thompson (possessing identical lipid A and core oligosaccharide structures but differing in the O-antigen polysaccharide chain) could be seen (P greater than 0.1). These results demonstrate that a nonpyrogenic O-antigenic polysaccharide hapten, when coupled to an immunogenic carrier protein, evokes immune responses which mediate significant, although modest, late-phase tolerance and is capable of partly reducing the pyrogenic activity of the O-antigenic homologous lipopolysaccharide.
Evidence that a non-O1 Vibrio cholerae produces enterotoxin that is similar but not identical to cholera enterotoxin
Authors: Yamamoto K , Takeda Y , Miwatani T , Craig J P
Published: January 2020

Cholera-like enterotoxin produced by a non-O1 strain of Vibrio cholerae, S7 (S7 enterotoxin), isolated from human diarrheal stool, was purified, and its physicochemical, biological, and immunological properties were compared with those of cholera enterotoxin from V. cholerae O1 569B (CT) and an enterotoxin produced by another non-O1 V. cholerae (E8498 enterotoxin) reported previously (Yamamoto et al., Infect. Immun. 39:1128-1135, 1983). The purified S7 enterotoxin had physicochemical properties different from those of CT and E8498 enterotoxin. S7 enterotoxin had greater relative mobility in conventional polyacrylamide gel disc electrophoresis and a lower isoelectric point, and its B subunit was smaller than those of CT and E8498 enterotoxin. The results of sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis suggested that the size of the aggregate of the B subunits of S7 enterotoxin is larger than that of CT and E8498 enterotoxin. The biological and immunological properties of S7 enterotoxin were indistinguishable from those of CT and E8498 enterotoxin. These results indicate that non-O1 vibrios may produce more than one kind of cholera-like enterotoxin: one which is identical to CT (E8498 enterotoxin type) and another which is not identical to CT (S7 enterotoxin type).
Systemic candidosis in silica-treated athymic and euthymic mice
Authors: Lee K W , Balish E
Published: January 2020

Intravenous silica injections were used to assess the role of macrophages in the resistance of BALB/c nude and euthymic mice to systemic candidosis. CFU of Candida albicans in the kidneys, livers, and spleens of saline- or silica-treated mice were enumerated at various times after inoculation with 10(4) viable yeast cells. The number of C. albicans organisms recovered from the kidneys of silica-treated euthymic mice was similar to the number recovered from saline-treated controls during the first 3 days of infection; however, at every assay period thereafter, the number of organisms recovered from the kidneys of silica-treated mice was dramatically reduced (100- to 1,000-fold). Conversely, silica-treated nude mice were no more susceptible to systemic candidosis than were saline-injected nude mice. Silica treatment did not alter the ability of treated or control mice to clear C. albicans from the liver and spleen. These results demonstrate that macrophages play an important role in susceptibility to Candida infections.
Different virulence of influenza A virus strains and susceptibility to pneumococcal otitis media in chinchillas
Authors: Giebink G S , Wright P F
Published: January 2020

We have previously shown that chinchillas infected with a multiply passaged laboratory strain of influenza A/NWS/33 (H1N1) develop negative middle-ear pressure; polymorphonuclear leukocyte oxidative, bactericidal, and chemotactic dysfunction; and increased susceptibility to pneumococcal otitis media. Because influenza A virus strains show different virulence in humans, three such strains were compared in the chinchilla model. Negative middle-ear pressure and tympanic membrane inflammation developed significantly more often in chinchillas infected with wild-type H3N2 virus than with either wild-type H1N1 virus or an attenuated, cold-adapted H3N2 vaccine strain, CR29. Marked depression in polymorphonuclear leukocyte chemiluminescent activity also developed significantly more often in H3N2 infected animals than in H1N1- or CR29-infected animals. Intranasal challenge of influenza virus-infected animals with type 7 Streptococcus pneumoniae resulted in a significantly greater occurrence of pneumococcal otitis media in H3N2-infected animals than in H1N1-, CR29-, or non-influenza-infected control animals. Clearance of pneumococci from nasal washings of animals infected with wild-type H3N2 was significantly delayed in comparison with the other groups. Thus, the previously demonstrated increased susceptibility to otitis media among children infected with H3N2 influenza virus may relate to the capacity of this strain to induce negative middle-ear pressure, polymorphonuclear leukocyte dysfunction, and alteration in the mucosal clearance of pneumococci.
Plasmid-mediated and temperature-regulated surface properties of Yersinia enterocolitica
Authors: Martinez R J
Published: January 2020

Enteropathogenic strains of Yersinia enterocolitica harbor a virulence plasmid which codes for a series of novel outer membrane proteins. The expression of these proteins on the outer membrane is temperature regulated: when cells are grown at 25 degrees C, these proteins are not exposed on the outer membrane, whereas they occur in high copy number when cells are grown at 37 degrees C. The majority of these proteins are externally exposed on the cell surface as evidenced by their susceptibility to proteolysis by exogenously added proteases. The expression of the plasmid-mediated proteins on the outer membrane does not favor adherence of the bacteria to intestinal epithelial cells in vitro. Cultures grown at 25 degrees C adhered to Henle cell monolayers, whereas those grown at 37 degrees C did so much less effectively. The presence of the proteins on the bacterial surface appears to be involved in rendering the cells resistant to the bactericidal effects of serum, i.e., 37 degrees C-grown cells were resistant to serum killing, and removal of the outer membrane proteins with pronase rendered them sensitive. Evidence is presented which strongly suggests that the plasmid-mediated proteins are synthesized and expressed on the cell surface either during or after transit of the ingested bacteria to the lamina propria. Some properties afforded to the cells by the outer membrane proteins are described.
Genetics of digalactoside-binding adhesin from a uropathogenic Escherichia coli strain
Authors: Normark S , Lark D , Hull R , Norgren M , Båga M , O'Hanley P , Schoolnik G , Falkow S
Published: January 2020

The uropathogenic strain Escherichia coli J96 mediates mannose-resistant hemagglutination owing to production of a digalactoside-binding adhesin. A cosmid clone from this strain has been isolated that, when harbored in E. coli K-12, expressed Pap pili and this adhesin (R. Hull et al., Infect. Immun. 33:933-938, 1981). By transposon mutagenesis and by the construction of a number of hybrid plasmid derivatives, we have demonstrated that about 8.5 kilobases of DNA is required to generate a mannose-resistant hemagglutination-positive phenotype in E. coli K-12 strain P678-54. The structural gene for the Pap pili monomer, papA, has been identified and mapped close to the promotor-proximal end of the Pap operon. Although strain P678-54 that harbored a Tn5 insertion within papA showed a mannose-resistant hemagglutination-positive phenotype, it was negative in a competitive enzyme-linked immunosorbent assay with anti-Pap pilus serum. This could mean that a Pap adhesin is encoded by a region on the Pap operon that is distinct from papA.
Natural killer cell activity in renal transplant recipients receiving cyclosporine
Authors: Gui X E , Rinaldo C R , Ho M
Published: January 2020

Normal subjects (n = 11) had a mean circulating natural killer (NK) cell activity of 188 lytic units per 10(7) peripheral mononuclear blood leukocytes. This activity was significantly enhanced by in vitro incubation with 500 U of alpha-interferon (+207 lytic units). The mean NK activity of renal transplant recipients on azathioprine (n = 17) or on cyclosporine (n = 17) studied at various times after transplantation was significantly decreased, as was the ability of interferon to enhance NK activity. In the cyclosporine group, interferon could not enhance NK titers 1 to 6 weeks after transplantation when the patients were on the highest doses of cyclosporine (mean, 1,002 mg/day) or when they were viremic for cytomegalovirus. After 18 weeks, when the patients received 546 mg/day or when viremia was no longer detected, the ability of interferon to enhance NK activity was more normal. Cyclosporine and cytomegalovirus infection may have a greater effect on the action of interferon on NK activity than on the NK titer per se. This defect may diminish the reserve of NK cells and contribute to post-transplant immunosuppression.
Nasopharyngeal flora and acute otitis media
Authors: Long S S , Henretig F M , Teter M J , McGowan K L
Published: January 2020

A semiquantitative nasopharyngeal culture was found to be sensitive and specific in predicting middle ear pathogens in children with acute bacterial otitis media. In nasopharyngeal specimens with growth of at least 1,000 colonies, the tympanocentesis isolate was present and was either the predominant isolate or accounted for 50% of growth in 16 of 16 children. Data suggest that virulence of nasopharyngeal organisms plays a role in the pathogenesis of acute otitis media. Qualitative differences were found in the nasopharyngeal flora of children with bacterial otitis media as compared with children with clinical otitis media and sterile tympanocentesis cultures, children with uncomplicated upper respiratory illness, and healthy children. Abundant growth of Haemophilus influenzae (greater than or equal to 50% total colony count) was associated with children with bacterial otitis media, and abundant Branhamella catarrhalis was associated with the others (P less than or equal to 0.01). Abundant growth of Streptococcus pneumoniae occurred frequently and regardless of clinical category. Antibiotic treatment of children with otitis media resulted in rapid quantitative and qualitative changes in nasopharyngeal flora.
Interleukin 2 enhances natural killer cell activity through induction of gamma interferon
Authors: Weigent D A , Stanton G J , Johnson H M
Published: January 2020

Highly purified interleukin 2 (IL 2), free of interferon activity, enhanced natural killer (NK) cell activity against tumor cells in mouse spleen cell cultures and in human peripheral lymphocyte cultures in a manner similar to that of interferon (IFN). We determined that IL 2 enhanced NK activity indirectly in a cascade manner by the induction of gamma IFN (IFN-gamma) in the cultures, which actually mediated the enhanced killing. Accordingly, lymphocyte cultures treated with IL 2 alone produced 10 to 100 U of IFN per ml in 6 to 24 h of culture. The IFN was typed as IFN-gamma by specific antibodies. Specific antibodies either to natural IFN-gamma or to a synthetic peptide corresponding to the human IFN-gamma N-terminal amino acids, when added to cultures treated with IL 2, completely blocked IL 2 enhancement of NK cell activity for both the mouse and human systems. IL 2-induced proliferation was not affected by the antibodies. Thus, the enhancement of NK cell activity by IL 2 is completely mediated by IL 2-induced IFN-gamma. The findings clearly indicate a cascade effect whereby one lymphokine (IL 2) induces the production of another. The latter lymphokine (IFN-gamma) then mediates an important biological effect (natural killing).
Natural cell-mediated cytotoxicity against Candida albicans induced by cyclophosphamide: nature of the in vitro cytotoxic effector
Authors: Baccarini M , Bistoni F , Puccetti P , Garaci E
Published: January 2020

We have recently reported the in vivo modulation of resistance to experimental Candida albicans infection by cyclophosphamide (150 mg/kg intraperitoneally) in mice and have shown that increased resistance to the microbial challenge occurs 12 to 21 days after treatment with the drug (Bistoni et al., Infect. Immun. 40: 46-55, 1983). The event is accompanied by the appearance of a highly candidacidal cell population in the spleen and the activation of a subpopulation of natural cytotoxic effectors reactive in vitro against YAC-1 tumor cells. We now provide evidence that these anti-YAC-1 cytotoxic effectors are clearly distinct from the cyclophosphamide-induced candidacidal effectors, which seem to belong to a macrophage-monocyte lineage. The enhanced cytotoxic activity induced by cyclophosphamide was not restricted to C. albicans but was also exerted against a panel of Candida strains.
Nonspecific suppressive effect of bovine herpesvirus type 1 on bovine leukocyte functions
Authors: Filion L G , McGuire R L , Babiuk L A
Published: January 2020

The effect of bovine herpesvirus type 1 on the specific and nonspecific immune response of calves was examined. Animals with or without prior aerosol exposure to Pasteurella haemolytica serotype A1 were aerosol challenged with 10(8) PFU of virus. Blood and serum samples were taken before and after virus challenge for determining cell-mediated, humoral, and neutrophil responses. A significant depression of the blastogenic responses to phytohemagglutinin, P. haemolytica, and Pasteurella multocida and of neutrophil chemotactic response was observed 4 to 7 days after challenge. However, the antibacterial activity of neutrophils was not significantly affected by virus exposure. Anti-bovine herpesvirus type 1 antibody responses were detected 11 days postchallenge. A significant elevation of the anti-P. haemolytica antibody response (day 0 versus day +11) was detected in animals previously exposed to P. haemolytica.
Differential effects of gamma interferon on expression of HLA class II molecules controlled by the DR and DC loci
Authors: Ameglio F , Capobianchi M R , Dolei A , Tosi R
Published: January 2020

Interferon-gamma affected the expression of the products of the immunoassociated antigen complex by a differential modulation of DR- and DC-locus-controlled molecules. In melanoma M14 cells treated with interferon-gamma, levels of DR molecules were increased two- to threefold, whereas levels of DC molecules were increased six- to sevenfold. Similar effects were induced on the two allelic products of each locus.