bluuebunny/crossref_metadata_2025 huggingface dataset:
Macrophage Dependence of Polyriboinosinic Acid-Polyribocytidylic Acid-Induced Resistance to Herpes Simplex Virus Infection in Mice
Authors: Martinez Douglas , Lynch Robert J. , Meeker Jeff B. , Field A. Kirk
Published: January 2020

The relative contributions of macrophages and lymphocytes to the induction of resistance to primary herpes simplex virus type 1 (HSV-1) infection by polyriboinosinic-polyribocytidylic acid complex [poly (I:C)] were investigated in C58 mice. The induction of resistance was found to be strongly dependent on macrophages compared to lymphocytes. Macrophage-deficient (silica-treated) mice produced less interferon and were not as responsive to prophylactic treatment of HSV-1 infections with poly (I:C) as were either normal, lymphocyte-deficient (cyclophosphamide-treated), or T-lymphocyte-deficient (anti-thymocyte serum-treated, adult-thymectomized) mice. Silica and cyclophosphamide treatments reduced the therapeutic activity of poly (I:C), whereas T-cell depletion did not have a significant effect. Similarly, the protection of mice with exogenous interferon was markedly reduced in silica-treated mice and moderately reduced in cyclophosphamide-treated mice, but unaffected in T-cell-deficient mice. Furthermore, suppression of HSV-1 plaque formation was obtained by cocultivation of infected mouse fibroblast monolayers with peritoneal (macrophage-rich) cells, but not with splenic (lymphocyte-rich) cells, from poly (I:C)-treated mice. Peritoneal cells did not protect heterologous (human) fibroblasts, suggesting that the protection of mouse embryo fibroblasts is mediated by interferon. Collectively, the data indicate that macrophages are required for the production of poly (I:C)-induced interferon and that macrophages and perhaps B-lymphocytes are important for mediating the protection against HSV-1 infection after interferon has been produced.
Identification of a cytotoxin produced by Legionella pneumophila
Authors: Friedman R L , Iglewski B H , Miller R D
Published: January 2020

Culture filtrates of Legionella pneumophila were cytotoxic for Chinese hamster ovary cells. The cytotoxin was found to be methanol soluble, heat stable, and stable from pH 5 through 8.
Effect of polychlorinated biphenyl on viral infections in mice
Authors: Imanishi J , Nomura H , Matsubara M , Kita M , Won S J , Mizutani T , Kishida T
Published: January 2020

Mice that were fed a diet containing 400, 200 or 100 microgram of polychlorinated biphenyls (PCB) per g were significantly more susceptible to Herpes simplex virus than mice that were fed a PCB-free diet. The mortality of mice that were fed a diet containing 400 or 200 microgram of PCB per g and infected with ectromelia virus was higher than that of normal control mice infected with virus. There was no significant difference in inducibility of interferon by polyinosinic acid-polycytoidylic acid between PCB-fed mice and control mice.
Chemotaxin-induced changes in cyclic adenosine monophosphate levels in human neutrophils
Authors: Marx R S , McCall C E , Bass D A
Published: January 2020

Incubation of the chemotactic agent N-formyl-methionyl-leucyl-phenylalanine with human neutrophils produced a rapid elevation of the intracellular level of cyclic adenosine monophosphate (cAMP). This cAMP spike occurred within 30 s after exposure and returned to normal by 5 min.
Immunochemical characterization of cross-reactivity of pneumococcal group 9 capsular polysaccharide types 9N, 9A, 9L, and 9V
Authors: Szu S , Lee C J , Carlo D , Henrichsen J
Published: January 2020

The chemical composition and immunochemical characterization of the four cross-reactive pneumococcal capsular polysaccharides within group 9 (types 9N, 9A, 9L, and 9V) were investigated. Their serological reactions were studied by using unabsorbed antisera prepared by immunizing rabbits with pneumococci of each of the four group 9 capsular polysaccharide types. Type 9A antiserum showed the most extensive cross-reactions with the four group 9 polysaccharides. Absorption with type 9N, 9L, or 9V polysaccharide removed 63, 96, or 87%, respectively, of the heterologous antibodies from the type 9A antiserum. All four of the group 9 polysaccharides contained glucose, N-acetylmannosamine, and glucuronic acid. In addition, types 9N and 9L had N-acetylglucosamine, and types 9A, 9L, and 9V contained galactose. Reduction of the uronic acid residues of the type 9 polysaccharides removed most of their homologous and much of their heterologous reactivities, indicating an important role for the uronic acid component in their antigenicity. The four group 9 polysaccharide preparations had comparable molecular sizes and only traces of protein and nucleic acid. Further studies to evaluate the most protective type among the group 9 strains to be included in the current pneumococcal vaccine are discussed.
Use of 51Cr-labeled mononuclear cells for measuring the cellular immune response in mouse lungs
Authors: Zarkower A , Scheuchenzuber W J , Ferguson F G
Published: January 2020

Spleen cells labeled with 51Cr were used in sensitized syngeneic mice to measure the degree of mononuclear cell infiltration into antigen-challenged tissues. With this method, increased cellular infiltration was found after footpad challenge of mice sensitized with sheep erythrocyte, Escherichia coli, and BCG antigens. Cellular response also was determined by using this technique in the lungs of mice sensitized with sheep erythrocytes and BCG. This procedure offers the opportunity to measure cellular infiltration, whether due to cellular or humoral influences, in tissues not easily accessible to conventional immunological manipulation.
Occurrence of antibodies against insect virus proteins in mammals: simple model to differentiate between passive exposure and active virus growth
Authors: Moore N F , McKnight L , Tinsley T W
Published: January 2020

Antibodies against an "enterovirus-like" virus of insects, cricket paralysis virus, occur in the sera of domestic animals. When these antibodies were used in combination with the immunoprecipitation of radiolabeled virus proteins from infected Drosophila cells in culture, it could be demonstrated that the animals were exposed to preformed virus.
Induction and suppression of cross-reactive antituberculosis immunity after Mycobacterium lepraemurium infection of mice
Authors: Lefford M J , Logie P S
Published: January 2020

Mice immunized with 10(8) live Mycobacterium lepraemurium in the footpad showed increased resistance to infection with BCG or M. tuberculosis R1Rv. This resistance could be transferred adoptively with lymphoid cells, signifying that the immunity was cross-reactive rather than nonspecific. Adoptive cross-reactive immunity to M. tuberculosis was also conferred by spleen cells from mice immunized with large doses of living or dead M. lepraemurium intravenously, a route of immunization that suppresses the induction of cell-mediated immunity to that organism. The presence of specific suppressor activity was sought in mice immunized intravenously with M. lepraemurium. It was found that mice preimmunized intravenously with living or dead M. lepraemurium and then infected with BCG did not confer levels of adoptive antituberculosis immunity as high as those conferred by mice immunized with BCG alone. Similarly, a mixture of BCG-sensitized and M. lepraemurium-sensitized cells did not convey as much immunity as BCG-sensitized cells alone, signifying suppression of the effector lymphocytes.
Binding of radiolabeled Staphylococcus aureus delta-toxin to human erythrocytes
Authors: Nolte F S , Kapral F A
Published: January 2020

The addition f [3H]isoleucine to a chemically defined medium resulted in the production of delta-toxin (DT) with a high specific radioactivity (0.47 microCi/mg). The purified tritium-labeled toxin ([3H]DT) was found to migrate in sodium dodecyl sulfate-polyacrylamide gel electrophoresis as a single band with a molecular weight of 1,600. Upon electrofocusing, [3H]DT yielded one major peak (pI = 5.90) and two minor peaks (pI = 5.10, 6.95) of radioactivity. The percentage of [3H]DT associated with pelleted fractions of intact erythrocytes or erythrocyte ghosts remained fairly constant over a 100-fold range of toxin concentrations. Erythrocyte ghosts, however, bound more [3H]DT than did intact erythrocytes when exposed to the same concentration of toxin. Erythrocytes maintained in isotonic sucrose were more susceptible to toxin than erythrocytes suspended in saline, but did not bind more [3H]DT. The binding of [3H]DT to erythrocyte ghosts was found to be temperature dependent from 0 to 20 degrees C but was constant from 20 to 50 degrees C.
Immunohistological study of the anatomic relationship of toxoplasma antigens to the inflammatory response in the brains of mice chronically infected with Toxoplasma gondii
Authors: Conley F K , Jenkins K A
Published: January 2020

The relationship of toxoplasma antigen(s) to the origin and long-term persistence of the mononuclear cell inflammatory infiltrate that is present in the brains of mice chronically infected with Toxoplasma gondii was studied by using the peroxidase-antiperoxidase immunohistochemical staining technique. C3H/Km mice were infected with the avirulent C37 strain of T. gondii and sequentially sacrificed over the ensuing 107 days. Comparable sections of each brain were prepared for routine light microscopy. Antisera to toxoplasma made in rabbits were used for immunohistological staining, and adjacent slides were also stained with conventional histological stains. The peroxidase-antiperoxidase stain demonstrated toxoplasma tissue cysts, tachyzoites, and intra- and extracellular antigen-antibody reaction products. Early infection was characterized by small tight clusters of free tachyzoites gaining access to brain substance in the absence of an inflammatory response. Once there was disruption of neural parenchyma, a mononuclear cellular infiltrate rapidly ensued. After the first days of infection, mononuclear cells were always present in all infected brains and were anatomically associated with some component of toxoplasma antigen(s). The histological picture of late infection suggested that recurrent episodes of hematogenous dissemination of tachyzoites occurred in infected mice and that such episodes were at least partially responsible for persistence of an antigenic stimulus.
Serum inhibition of merozoite dispersal from Plasmodium falciparum schizonts: indicator of immune status
Authors: Green T J , Morhardt M , Brackett R G , Jacobs R L
Published: January 2020

Specific immune serum was found to inhibit the dispersal of the merozoites from mature schizonts, thus interfering with their subsequent reinvasion of new host erythrocytes. This phenomenon is viewed as a protective mechanism against malaria which can be measured in vitro and reflects the immune status of the donor.
Vascular permeability activity of botulinum C2 toxin elicited by cooperation of two dissimilar protein components
Authors: Ohishi I , Iwasaki M , Sakaguchi G
Published: January 2020

Botulinum C2 toxin has vascular permeability as well as lethal activities. Both activities are elicited by cooperation of two dissimilar protein components, designated components I and II, which individually have very low activities. The vascular permeability activity of C2 toxin, demonstrated as blueing response after intravenous injection of Evans blue, was markedly enhanced by treatment with trypsin and was abolished by neutralization with either anti-component I or II serum. Inflammatory reactions, such as edema, congestion, and hemorrhage, were found at the site of intradermal injection of trypsinized C2 toxin. No vascular permeability activity was demonstrated by the intradermal injection of the toxin of Clostridium botulinum types A through F. These results indicate that C2 toxin has a novel biological activity, which is not possessed by the neurotoxin elaborated by C. botulinum types A through F. This suggests that C2 toxin causes lethality in a different way from that of botulinum neurotoxin, which is known to inhibit the presynaptic release of acetylcholine at the neuromuscular junction.
Role of natural killer cells in Pichinde virus infection of Syrian hamsters
Authors: Gee S R , Chan M A , Clark D A , Rawls W E
Published: January 2020

Pichinde virus produced a fatal infection in adult MHA hamsters but not LSH hamsters after intraperitoneal inoculation. After footpad inoculation, an 8-day swelling response was observed in LSH but not MHA hamsters; however, both strains survived infection by this route. Examination of the kinetics of viral replication in the two hamster strains inoculated by the two routes revealed a correlation between infectious centers and natural killer activity in cells obtained from spleens and popliteal lymph nodes. A subpopulation of cytolytic and infected cells which sedimented at about 3.0 to 4.5 mm/h in albumin gradients was found in greater numbers in MHA than in LSH hamsters. These data suggest that one factor contributing to the fatal outcome of Pichinde virus infection in MHA hamsters is the presence of excessive numbers of splenic target cells which possess properties of natural killer cells.
Effect of bacterial aggregation on the adherence of oral streptococci to hydroxyapatite
Authors: Liljemark W F , Bloomquist C G , Germaine G R
Published: January 2020

Several in vitro assay systems to measure the adherence of human dental plaque bacteria to solid surfaces such as teeth, glass, and hydroxyapatite have been published. In many studies a variety of macromolecular solutes have been used to study the adherence process. Often these solutes are able to aggregate the test bacterial and thus may alter the outcome of adherence experiments. In this study, the effects of the aggregation of Streptococcus sanguis on adherence to spheroidal hydroxyapatite is described. Adherence of preformed aggregates and of bacteria which were aggregating during the adherence reaction was examined. Bacteria were aggregated with whole saliva, concanavalin A, and wheat germ lectin. Further effects of the coaggregation of S. mitis and Actinomyces viscosus to saliva-coated spheroidal hydroxyapatite are presented. These studies suggest that formation of large aggregates resulted in a decrease in the numbers of organisms which adhered. In contrast, the formation of small aggregates actually increased the numbers of bacteria that adhered. All increases in adherent bacteria occurred at low concentrations of aggregating substance in which visible bacterial aggregation was not evident. The data indicate that adequate dose-response experiments must be performed to ensure that solutes used as probes to study adherence mechanisms do not affect the adherence simply as a result of aggregation of the test microorganisms.
Influence of oxygen on respiration and glucose catabolism by Treponema pallidum
Authors: Barbieri J T , Cox C D
Published: January 2020

Oxygen consumption by Treponema pallidum was observed to be glucose dependent. Treponemes consumed O2 to a low dissolved O2 concentration of 0.01 mumol of O2 per ml when respiration ceased. A fermentative degradation of glucose occurred during the maintenance of treponemes at 0.01 mumol of O2 per ml. Although the initial rate of respiration was independent of the dissolved O2 concentration, the respiration rate decreased upon prolonged incubation at 0.20 mumol of O2 per ml as compared with the respiration rate at 0.7 mumol of O2 per ml. Oxygen was determined to be the major electron acceptor during the oxidative metabolism of glucose. Acetate formation paralleled the respiration rate of the treponemes, whereas lactate production appeared to be independent of respiration. Accumulation of pyruvate occurred at 0.20 mumol of O2 per ml but not at 0.07 mumol/ml. Analyses of enzyme activities in cell-free extracts from treponemes maintained at either 0.07 or 0.20 mumol of O2 per ml for 4 h revealed a loss of pyruvate decarboxylase activity at the higher dissolved O2 concentration, suggesting the inactivation of pyruvate oxidase.
Susceptibility differences of inbred strains of mice to blastomycosis
Authors: Morozumi P A , Halpern J W , Stevens D A
Published: January 2020

The susceptibility of inbred strains of mice to pulmonary blastomycosis was studied to derive information relevant to host resistance and genetic background. Initial studies with eight strains with various H-2 backgrounds revealed the C3H/HeJ strain to be highly susceptible and DBA/1J mice to be resistant. These observations were confirmed with various challenge inocula. These differences were not dependent on the size of the challenge, the strain of Blastomyces dermatitidis, host age, or ability of the challenge to penetrate to the lower airways. Differences between the susceptible and resistant strains in lymphocyte proliferation in vitro and delayed-type hypersensitivity in vivo after nonlethal subcutaneous infection were not demonstrated; the susceptible strain made a significantly greater antibody response to blastomyces antigens as determined by an enzyme-linked immunosorbent assay. The resistance of the C3H/HeN strain of mice, which differs from the C3H/HeJ in sensitivity to lipopolysaccharide and lacks the macrophage cytotoxicity defect of the latter, suggests that the susceptibility of C3H/HeJ mice is not related to their C3H background or the H-2 locus. As the A/HeJ strain, which also has a macrophage cytotoxicity defect, was found in this study to be the second most susceptible strain, this also suggests macrophages as the subject for further study with respect to the mechanism of genetic resistance to this infection.
Influence of H-2 and non-H-2 genes on resistance to murine cytomegalovirus infection
Authors: Grundy J E , Mackenzie J S , Stanley N F
Published: January 2020

The resistance of adult mice to acute lethal infection with murine cytomegalovirus is controlled by genes linked to the H-2 complex. The k haplotype is approximately 10 times more resistant than the b or d haplotypes. Susceptibility is inherited as a completely dominant trait. At least two genes within the H-2 complex are involved, one mapping to the K/IA subregion and the other to the D subregion. The data suggest that interactions may occur between these K- and D-end genes which further affect resistance to the virus. The precise mechanism of H-2 gene control of resistance to murine cytomegalovirus remains to be elucidated. Non-H-2 linked genes also affect resistance to the virus, particularly in the C57BL genetic background, which is associated with an increased resistance to murine cytomegalovirus. Newborn mice of all strains are equally susceptible: both the H-2- and the non-H-2-associated resistances develop in the first few weeks of life and are retained up to at least 18 months of age.
Murine Immunoprotective Activity of
Klebsiella pneumoniae
Cell Surface Preparations: Comparative Study with Ribosomal Preparations
Authors: Fournier Jean-Michel , Jolivet-Reynaud Colette , Riottot Marie-Madeleine , Jouin Hélène
Published: January 2020

Cell surface preparations and ribosomal preparations were extracted from
Klebsiella pneumoniae.
Agar gel diffusion with antisera to cell surface preparations or ribosomal preparations indicated common antigenic components among the preparations. Lipopolysaccharide and capsular polysaccharide were identified in the cell surface preparations. These results and the previous identification of lipopolysaccharide and capsular polysaccharide in ribosomal preparations suggest that these antigens are responsible for the immunochemical cross-reactivity observed among these two bacterial extracts. Active protection could be induced in mice by these two preparations. On a dry-weight basis, cell surface preparations provided better immunoprotective activity than did ribosomal preparations. However, the 50% protective dose of both preparations is practically the same on the basis of their capsular polysaccharide content. These results are consistent with the hypothesis that the immunoprotective moiety of ribosomal preparations is the contaminating cell surface antigens. Furthermore, the low level of nucleotidic components detected in purified cell surface preparations led us to infer that the immunoprotective activity of capsular polysaccharide may not be dependent on the adjuvant activity of ribonucleic acid. The involvement of capsular polysaccharide in the immunoprotective capacity of cell surface preparations is demonstrated either by using a degradation of this antigen by
K. pneumoniae
bacteriophage K2-associated glycanase or by using a preparation extracted from a noncapsulated mutant of
K. pneumoniae.
Nevertheless, the low protective ability of purified capsular polysaccharides is in contrast to its greater activity when induced in bacterial cell surface preparations. The protective activity of
K. pneumoniae
capsular polysaccharide may be dependent on its association with other surface antigenic components present in cell surface preparations or may be dependent on its native form in the bacterial cell surface.
Glucan-enhanced immunogenicity of killed erythrocyte stages of Plasmodium berghei
Authors: Holbrook T W , Cook J A , Parker B W
Published: January 2020

Intravenous injections of glucan simultaneously with Formalin-killed erythrocytic stages of Plasmodium berghei elicited a greater degree of resistance in mice against subsequent infection with viable parasites than injections of killed erythrocytic stages alone. In two experiments with P. berghei strain NK 65, 100% of mice immunized with the glucan-dead parasite preparation survived challenge, whereas only 28.6% of mice receiving dead parasites alone survived. In the third experiment, using P. berghei strain NYU-2, the same proportion of mice survived after immunization with glucan and dead parasites as with dead parasites alone (i.e., 10 of 11 in each group), but mice immunized with the glucan-dead parasite preparation experienced parasitemias of significantly less intensity and shorter duration than mice which received only dead parasites before infection. Inoculation of glucan alone or with normal erythrocytes conferred no protection against challenge.
Protection of rabbits against experimental pasteurellosis by a streptomycin-dependent Pasteurella multocida serotype 3:A live mutant vaccine
Authors: Lu Y S , Pakes S P
Published: January 2020

Pasteurella multocida (serotype 3:A) was isolated from a rabbit with clinical signs of suppurative rhinitis. This P. multocida strain was mutagenized with N-methyl-N'-nitro-N-nitrosoguanidine to obtain a genetically stable streptomycin-dependent mutant, from which a life vaccine was prepared. Pasteurella-free rabbits were inoculated intranasally three times at weekly intervals and challenged intranasally with a virulent serotype 3:A rabbit P. multocida isolate 2 weeks after the third vaccination. The rabbits were killed 2 to 3 weeks later. The vaccine did not cause clinical disease, death, or gross or microscopic lesions. Furthermore, the vaccine protected the challenge rabbits from developing clinical disease, death, and gross lesions. However, mild focal lung lesions were noted in several of the vaccinated-challenged animals. In contrast, nonvaccinated-challenged rabbits developed pyrexia and anorexia. Furthermore, three of four of these rabbits died with severe gross lesions including pyothorax, suppurative pericarditis, and fibrinopurulent pneumonia. Microscopically, the four nonvaccinated rabbits had moderate to severe suppurative pneumonia and mild to moderate suppurative rhinitis, and two had mild tympanitis. The mutant vaccine did not appear to colonize the nasal cavities. The vaccine prevented the colonization of the virulent challenge organism in lungs, liver, spleen, genital tracts, and blood, but not the nasal cavities.
Studies of phospholipase C (heat-labile hemolysin) in Pseudomonas aeruginosa
Authors: Berka R M , Gray G L , Vasil M L
Published: January 2020

The chromogenic substrate p-nitrophenylphosphorylcholine was used to measure phospholipase C (heat-labile hemolysin) production by clinical strains of Pseudomonas aeruginosa. Analysis of strains from various types of infection showed that phospholipase C production by urinary tract isolates was significantly greater than that by lung, blood, or other isolates (e.g., wounds, etc.). The above method was also found to be effective for the isolation of several classes of phospholipase C mutants.
Correlation between in vivo anti-Pseudomonas and anti-Candida activities and clearance of carbon by the reticuloendothelial system for various muramyl dipeptide analogs, using normal and immunosuppressed mice
Authors: Fraser-Smith E B , Waters R V , Matthews T R
Published: January 2020

A linear correlation coefficient analysis, comparing in vivo anti-infective and reticuloendothelial stimulating activity of several different analogs of N-acetylmuramyl-L-alanyl-D-isoglutamine (muramyl dipeptide) suggests that the macrophage is an important target cell for these immunomodulating compounds. The increase in protection against infections of Candida albicans or Pseudomonas aeruginosa in normal or immunosuppressed mice after treatment with 18 different glycopeptides was found to correlate with the degree of clearance of colloidal carbon particles from the blood by the reticuloendothelial system after treatment with the same muramyl dipeptide analogs. The compound which gave the greatest protection in all four assays was N-acetylmuramyl-L-alpha-aminobutyryl-D-isoglutamine followed by N-acetyl-nor-muramyl-L-alanyl-D-isoglutamine. Both analogs were better than the parent muramyl dipeptide. Whether macrophage stimulation alone is responsible for the anti-infective properties of these compounds has not yet been determined.
Persistent infection with bovine herpesvirus type 1: rabbit model
Authors: Rock D L , Reed D E
Published: January 2020

Persistent infection with bovine herpesvirus type 1 (BHV-1) was established in all rabbits after conjunctival inoculation of virus. Spontaneous reactivations of BHV-1 with and without the appearance of recurrent ocular lesions were observed in persistently infected rabbits. BHV-1 was reactivated predictably and shed from all persistently infected rabbits after the administration of dexamethasone. During all reactivations, BHV-1 isolation was restricted to the inoculated eye.
Failure of bacterial lipopolysaccharide to elicit a cytostatic effect on Plasmodium vinckei petteri in C3H/HeJ mice
Authors: Rzepczyk C M , Clark I A
Published: January 2020

Malarial parasites, Plasmodium vinckei petteri, taken from lipopolysaccharide (LPS) high-responder (C3H/HeJGiFWeHi) mice which had been injected 7 to 8 h previously with either Escherichia coli LPS B or LPS W incorporated the purine nucleotide precursor hypoxanthine more slowly in an in vitro assay than parasites taken from saline-injected controls. In contrast, malarial parasites taken from LPS low-responder C3H/HeJ mice after injection of either LPS B or LPS W did not show reduced levels of hypoxanthine incorporation. These differing results with LPS high- and low-responder mouse strains demonstrated that the cytostatic effect on the parasites seen in the high-responder strain was not due to the direct action of LPS and implied that the cytostasis was mediated via host lymphoreticular cells. Furthermore, the failure of LPS B, a lipid A-associated protein-containing LPS preparation, to elicit a cytostatic effect on P. vinckei petteri in C3H/HeJ mice suggested that the LPS-induced effector mechanisms acting against malarial parasites may be similar to those reported against bacteria and tumors.
Modulation of the host immune response as a result of Chlamydia psittaci infection
Authors: Lammert J K , Wyrick P B
Published: January 2020

After intraperitoneal injection of mice with infectious, inactivated, or envelope preparations of the elementary body of Chlamydia psittaci, lymphocyte transformation of spleen cells to the mitogens concanavalin A, phytohemagglutinin, and lipopolysaccharide was significantly reduced 1 and 2 weeks postinjection. Lymphocyte response returned to the control values by 4 weeks. Similarly, transformation of cells by chlamydial antigen was not detected until 4 weeks postinjection. Injection of the noninfectious intracellular reticulate body, in contrast, had little effect on transformation of cells to concanavalin A. When control spleen cells were incubated with infectious or inactivated elementary bodies in vitro, response to all three mitogens was also reduced. The sooner the organisms were added after the addition of mitogen, the greater the reduction in transformation. Incubation with elementary body envelopes and reticulate bodies had no effect on lymphocyte transformation of the spleen cells to concanavalin A. The relationship between the observed ability to reduce the response in the in vitro assay of lymphocyte transformation and the actual in vivo establishment of infection is discussed.
Atrophy of the thymic cortex in mice with granulomatous schistosomiasis mansoni
Authors: Wellhausen S R , Boros D L
Published: January 2020

Thymic histopathology and granulomatous hypersensitivity were examined in CBA/J mice infected with varying numbers of Schistosoma mansoni worms. At the acute phase (8 weeks) of infection, the thymi of infected mice showed depletion of cortical lymphocytes that resulted in loss of distinction in the corticomedullary region. The degree of cortical depletion correlated directly with the intensity of infection, as assessed by total egg burden of the liver. Adrenalectomy of heavily infected mice 5 to 6 weeks after infection did not alter the course of cortical lymphocyte depletion. Thymus mass was diminished by as much as 80% in heavily infected mice. However, the thymi of lightly infected mice which survived 20 weeks of infection did not differ in histology or total tissue mass from age-matched uninfected controls. Adult thymectomy at 3 weeks of infection did not abrogate the spontaneous modulation (diminution) of granuloma formation in 20-week infected mice, although spleen cells from these mice failed to adoptively transfer suppression. Heavily infected mice which did not survive beyond the acute phase (8 to 9 weeks) of infection displayed a diminished granulomatous response that was partially restored by thymectomy carried out at 5 to 6 weeks of infection. Spleen cells from heavily infected mice (8 weeks) adoptively suppressed the granulomatous response in lightly infected recipients. It is concluded that histological changes observed in the thymus concurrent with egg dissemination and granulomatous hypersensitivity correlated with T cell-mediated regulatory events.
Chronic, patent Plasmodium berghei malaria in splenectomized mice
Authors: Eling W M
Published: January 2020

It was shown that splenectomized mice could develop a certain resistance to Plasmodium berghei but usually no real immunity, since the infection became chronic, often with high parasitemias. A patent infection lasting at least 2 weeks was necessary for the development of this degree of protection. Prolonged suppression to subpatent levels (sulfonamide treatment), rather than radical cure (chloroquine), after 2 weeks of patency yielded a higher proportion of mice resistant to superinfection. An increasing proportion of B10LP, but not C57BL/Rij or BALB/c, mice cleared their chronic infection spontaneously in time. Chronic patent infections were accompanied by anemia, elevated serum glutamate oxaloacetate transaminase levels, indicating liver pathology, and decreased immune reactivity, but the magnitude to these pathological changes was limited compared with changes in primary, lethal infections in intact controls. Parasitemia and pathology did not always develop synchronously.
Susceptibility to enteric botulinum colonization of antibiotic-treated adult mice
Authors: Burr D H , Sugiyama H
Published: January 2020

The relationship between the indigenous intestinal microflora of adults and their resistance to the enteric botulinum infection of infant botulism was studied. Orogastric challenges of 10(5) type A Clostridium botulinum spores were given to adult mice whose gut flora had been altered by feedings of a mixture of erythromycin and kanamycin sulfate. From 80 to 100% of mice became infected when challenged 15 to 60 h after antibiotic administration. The mean infective dose of 2 X 10(4) spores per mouse for challenges given 23 h after antibiotic administration contrasted with the failure of 10(6) spores to infect control mice. Botulinum-colonized mice remained asymptomatic, although colonization lasted up to 5 days, and total botulinum toxin in the gut on days 3 and 4 postchallenge averaged 3,400 and 2,200 mouse intraperitoneal mean lethal doses. The mean infective dose for inocula placed in the colon of antibiotic-treated mice was 10(3) spores per mouse, and C. botulinum multiplied in the cecum as well as in the colon.
Application of RNase T1 one- and two-dimensional analyses to the rapid identification of foot-and-mouth disease viruses
Authors: La Torre J L , Underwood B O , Lebendiker M , Gorman B M , Brown F
Published: January 2020

The analysis of several isolates of foot-and-mouth disease virus by RNase T1 fingerprinting of the 32P-labeled RNA is described. It has been shown that use of the 35S induced RNA instead of the virus particle RNA has two advantages. (i) About 40 times more radioactivity is incorporated into the induced RNA. (ii) The RNA can be prepared much more rapidly, thus increasing the value of the technique in rapid diagnosis. One-dimensional maps, in which the RNase T1 oligonucleotides are separated according to size, have been shown to provide a valuable screening method for distinguishing between viruses. Those viruses giving similar one-dimensional maps also gave similar two-dimensional maps. The value of using the length of the polycytidylic acid tract of foot-and-mouth disease virus as a diagnostic tool is also discussed.
Interferon independence of genetically controlled resistance to flaviviruses
Authors: Brinton M A , Arnheiter H , Haller O
Published: January 2020

Flavivirus-resistant C3H/RV mice injected with sheep anti-interferon globulin and then infected with either West Nile or yellow fever virus survived and displayed no disease symptoms. Also, treatment of embryo fibroblast cultures prepared from C3H/RV or congenic susceptible C3H/HE mice with anti-interferon serum resulted in an increased yield of West Nile virus from both types of cultures, but the amount of infectious virus produced by resistant cultures remained 1 to 1.5 logs lower than that produced by susceptible cell cultures. These results indicate that the mode of expression of the flavivirus resistance gene differs significantly from that of the Mx gene conferring resistance to influenza virus-induced disease in A2G mice.
Influenza A virus-induced polymorphonuclear leukocyte dysfunction in the pathogenesis of experimental pneumococcal otitis media
Authors: Abramson J S , Giebink G S , Quie P G
Published: January 2020

The role of influenza A virus-induced polymorphonuclear leukocyte and eustachian tube dysfunction in the pathogenesis of acute purulent otitis media was studied in chinchillas. Polymorphonuclear leukocyte function, middle ear pressure, and the incidence of pneumococcal otitis media were observed after intranasal inoculation with influenza A virus, Streptococcus pneumoniae, or both. Results showed that depressed negative middle ear pressure and polymorphonuclear leukocyte chemiluminescence and chemotactic activity occurred after influenza inoculation, but not after inoculation with pneumococcus alone. The greatest incidence of pneumococcal otitis media occurred when the pneumococcus was inoculated just before the time of influenza-induced polymorphonuclear leukocyte dysfunction and negative middle ear pressure. Animals that had unilateral tympanostomy tubes placed before inoculation of influenza with pneumococcus showed no difference in the occurrence of pneumococcal otitis media in ventilated and nonventilated ears, suggesting that polymorphonuclear leukocyte dysfunction contributes more to the pathogenesis of pneumococcal otitis media than does negative middle ear pressure in this animal model.
Corticosterone regulation of the effector function of malarial immunity during pregnancy
Authors: van Zon A A , Eling W M , Hermsen C C , Koekkoek A A
Published: January 2020

In the experimental Plasmodium berghei mouse model, as in human malaria, reduced maternal responsiveness and even loss of immunity were observed during pregnancy. Loss of immunity in the second half of pregnancy occurred during a period of elevated plasma corticoid levels. Further analysis showed that plasma corticoid levels were significantly higher in immunodepressed mice than in mice that remained immune throughout pregnancy. Plasma corticosterone levels differed increasingly from those in mice with persistent immunity towards recrudescence. In nonimmune infected controls, however, only a slight increase in plasma corticosterone, already present during the subpatent period, was measured. Blocking the maternal corticoid production by adrenalectomy delayed the increase of plasma corticosterone (fetoplacental origin) and reduced the number of mice that lost immunity during pregnancy considerably. The role of various plasma corticoid levels in the regulation of effector function of immunity during pregnancy is discussed.
Energy metabolism of the contagious equine metritis bacterium
Authors: Lindmark D G , Jarroll E L , Timoney P J , Shin S J
Published: January 2020

The energy metabolism of the English E-CMO strain of contagious equine metritis bacterium was studied in whole cells and cell extracts. This bacterium appears to have an active Krebs cycle and probably obtains energy by oxidative phosphorylation since glycolysis and the hexose monophosphate pathways appear to be absent. These conclusions are based on the findings that [U-14C]glucose incorporation by this bacterium is below the level of detection, and that respiration is stimulated by Krebs cycle intermediates (i.e., malate, citrate, and succinate), but not by glucose, fructose, maltose, or sucrose. Furthermore, support comes from the fact that enzymes generally associated with the Krebs cycle and electron transport (i.e., malate dehydrogenase, succinate dehydrogenase, isocitrate dehydrogenase, fumarate hydratase, malate dehydrogenase [decarboxylating], cytochrome oxidase, superoxide dismutase, NADH dehydrogenase, and catalase) were detected. Those enzymes normally associated with glycolysis and the hexose monophosphate pathways (i.e., hexokinase, glucose 6-phosphate dehydrogenase, fructose biphosphate aldolase, glycerol 3-phosphate dehydrogenase, phosphoenolpyruvate carboxykinase, pyruvate kinase, phosphate acetyl transferase, acetate kinase, alcohol dehydrogenase, and lactate dehydrogenase) were below the level of detection.
Ultrastructural localization of interferon receptors on the surfaces of cultured cells and erythrocytes
Authors: Kushnaryov V M , Sedmak J J , Bendler J W , Grossberg S E
Published: January 2020

The bindings sites for interferon (IFN) on the limiting cell membranes of human and mouse fibroblasts and erythrocytes were revealed by an indirect immunoferritin technique. Mouse IFN-beta and human IFN-beta of high specific activity were used with the corresponding purified antibodies. Species-specific IFN binding was demonstrated by ferritin deposition on human erythrocytes and fibroblast membranes treated with human IFN and on mouse erythrocytes and fibroblast membranes treated with mouse IFN, but not on human erythrocytes or fibroblast membranes treated with mouse IFN. IFN binding sites on fibroblasts were located on regions of membranes between microvilli, whereas diphtheria toxin receptors were demonstrated mainly on microvilli. IFN binding altered the diphtheria toxin after IFN treatment. This reduced toxicity correlated with a decrease in the quantity of receptors for diphtheria toxin on the cell membrane. Thus, the species-specific binding of IFN appears to depend on membrane receptors in discrete regions of the limiting membrane which are present not only on functionally responsive fibroblasts but also on erythrocytes.
Membrane alteration responsible for the induction of gamma interferon
Authors: Dianzani F , Monahan T M , Santiano M
Published: January 2020

Induction of gamma interferon in human lymphoid cells cultures appears to be dependent upon specific membrane-mediated events and calcium flux. Since blastic response had been observed after enzymic oxidation of membrane-bound galactose residues, we used this system to study the nature of membrane alterations responsible for the activation of interferon induction. The results of these experiments suggest that a membrane oxidation is essential for interferon induction and depletion of calcium abolishes interferon production. In addition, we have shown that interferon induction by concanavalin A, phytohemagglutinin, and staphylococcal enterotoxin A, but not by galactose oxidase is prevented by cleavage of N-acetylneuraminic acid residues. Thus, interferon induction in human lymphoid cell cultures by galactose oxidase, concanavalin A, phytohemagglutinin, staphylococcal enterotoxin A, and NaIO4 appears to reside in terminal oligosaccharides of the cell membrane. How this specific membrane event relates to the derepression of the interferon locus is being actively pursued.
Antigenicity of Neisseria gonorrhoeae outer membrane protein(s) III detected by immunoprecipitation and Western blot transfer with a monoclonal antibody
Authors: Swanson J , Mayer L W , Tam M R
Published: January 2020

Some properties of gonococcal outer membrane III were studied by using a monoclonal antibody (2E6) in Western blot transfer and immunoprecipitation reactions. By Western blot, the 2E6 monoclonal had a single antigenic target: outer membrane protein III. All three gonococcal strains examined exhibited identical reactivities for their protein(s) III with this monoclonal. When 125I-labeled gonococci were incubated with monoclonal antibody 2E6, lysed in Zwittergent, and antibody-antigen complexes were immunoprecipitated with protein A-Sepharose, both outer membrane proteins I and III were present in the immunoprecipitates regardless of the gonococcal strain used. Exposure of gonococci to Iodogen and 2-mercaptoethanol influences the electrophoretic migration characteristics of protein(s) III in polyacrylamide gel electrophoresis with sodium dodecyl sulfate; the antigenicity of protein(s) III was unaltered when assessed by Western blot transfer after reaction with Iodogen or 2-mercaptoethanol. These data demonstrate that outer membrane protein III is a surface-exposed antigenic moiety common to diverse strains of gonococci.
Effect of estradiol on chlamydial genital infection of female guinea pigs
Authors: Rank R G , White H J , Hough A J , Pasley J N , Barron A L
Published: January 2020

Female guinea pigs were treated daily with 1 mg of beta-estradiol-3-benzoate intramuscularly beginning 14 days before intravaginal inoculation with the chlamydial agent of guinea pig inclusion conjunctivitis and continuing during the course of the infection. Treatment with estradiol was found to markedly influence the course of genital infection with the chlamydial agent of guinea pig inclusion conjunctivitis, producing infections of greater intensity and longer duration than those in control animals. Moreover, pathogenesis was altered in that ascending infection was observed, resulting in endometritis, cystic salpingitis, and cystitis. Infection in the controls was limited to the cervix and vagina. Estradiol treatment increased the apparent number of infected cells in the cervix and vagina as detected by histopathology and immunofluorescent staining. Humoral and cell-mediated immune responses to the chlamydial agent of guinea pig inclusion conjunctivitis were comparable in estradiol-treated and untreated animals. These data indicate that hormonal manipulation may have profound effects on the course of chlamydial genital infections.
In Vitro Inhibition of
Pseudomonas aeruginosa
Elastase by Metal-Chelating Peptide Derivatives
Authors: Kessler Efrat , Israel Mary , Landshman Nahum , Chechick Aaron , Blumberg Shmaryahu
Published: January 2020

Pseudomonas aeruginosa
elastase is a zinc metalloendopeptidase, probably responsible for the tissue destruction observed during infections with this organism. The elastase of a virulent
Pseudomonas aeruginosa
strain (Habs serotype 1) was isolated and found to have a molecular weight of 35,000; it readily degraded elastin and cartilage proteoglycans. A series of amino acid and peptide derivatives containing the metal-chelating moieties hydroxamate, phosphoryl, or thiol were synthesized and tested as potential inhibitors of the enzyme. Inhibition constants (

K
i

s) for the compounds were determined with the chromophoric substrate furylacryloyl-glycyl-
l
-leucyl-
l
-alanine. The hydroxamic acid derivatives of benzyloxycarbonyl-glycine, benzyloxycarbonyl-
l
-leucine and benzyloxycarbonyl-
l
-phenylalanine had inhibition constants in the range of 11 to 28 μM. The 2-mercaptoacetyl derivatives of
l
-leucyl-
d
-phenylalanine and
l
-leucyl-
l
-phenylalanine had

K
i

values of 34 and 1.5 μM, respectively, demonstrating the stereospecificity of the inhibition. The most potent inhibitors tested were 2- mercaptoacetyl-
l
-phenylalanyl-
l
-leucine and phosphoryl-
l
-leucyl-
l
-phenylala-nine (

K
i

= 0.2 μM). Similar compounds lacking the metal-chelating moiety were about 3 orders of magnitude poorer inhibitors. When the inhibition of the enzyme activity towards azocasein, elastin, or cartilage was examined, inhibitor concentrations approximately 50-fold higher than the respective

K
i

s were required to obtain 60 to 90% inhibition. Virtually complete inhibition was achieved with these substrates at inhibitor concentrations 500-fold higher than the respective

K
i

s (0.1 to 14 mM). Although, 2-mercaptoacetyl-
l
-phenylalanyl-
l
-leucine and phosphoryl-
l
-leucyl-
l
-phenylalanine exhibited the same affinity to the enzyme, the latter was inferior in inhibiting cartilage proteoglycan degradation. 2-Mercaptoacetyl-
l
-phenylalanyl-
l
-leucine represents a class of potent elastase inhibitors that might prove useful in the management of
P. aeruginosa
infections.
Immunological and Physicochemical Characterization of Heat-Labile Enterotoxins Isolated from Two Strains of
Escherichia coli
Authors: Clements John D. , Flint Dianne C. , Klipstein Frederick A.
Published: January 2020

Heat-labile enterotoxins from
Escherichia coli
strains of human and porcine origins had identical subunit composition, arrangement, and size in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Immunological differences recently described by others were shown to reside exclusively in the B subunits.
Isolation and characterization of the sheep erythrocyte receptor for acholeplasmal lipoglycans
Authors: Al-Samarrai T H , Smith P F , Lynn R J
Published: January 2020

A receptor specific for lipoglycans from Acholeplasma axanthum and Acholeplasma granularum was isolated from sheep erythrocyte stroma by extraction with n-pentanol and permeation chromatography. The purified receptor appeared as one band on sodium dodecyl sulfate-polyacrylamide gels and stained with Coomassie blue, periodate-Schiff reagent, and Sudan black. It was distinct from the erythrocyte receptor for gram-negative lipopolysaccharides and the glycophorin receptor for certain species of Mycoplasma. Periodate oxidation and trypsin did not affect the receptor activity in intact erythrocytes, but the purified receptor was susceptible to proteolytic digestion. Specific receptors, sensitive to trypsin digestion, could be isolated from rabbit kidney and cultured rabbit epidermal cell membranes. These could be distinguished from the receptor from erythrocytes by their solubility in n-pentanol. The segment of the lipoglycan molecule which binds to these receptors was not lipoidal in nature and was distinct from the specific antigenic determinants of the lipoglycans.