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In Vitro Investigation of Host Resistance to Toxoplasma gondii Infection in Microglia of BALB/c and CBA/Ca Mice

Freund, Yvonne R.; Zaveri, Naunihal T.; Javitz, Harold S.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /02/2001 Português
Relevância na Pesquisa
45.52%
Toxoplasmic encephalitis (TE) is a life-threatening disease of immunocompromised individuals and has increased in prevalence as a consequence of AIDS. TE has been modeled in inbred mice, with CBA/Ca mice being susceptible and BALB/c mice resistant to the development of TE. To better understand the innate mechanisms in the brain that play a role in resistance to TE, nitric oxide (NO)-dependent and NO-independent mechanisms were examined in microglia from BALB/c and CBA/Ca mice and correlated with the ability of these cells to inhibit Toxoplasma gondii replication. These parameters were measured 48 h after stimulation with lipopolysaccharide (LPS) gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), or combinations of these inducers in T. gondii-infected microglia isolated from newborn mice. CBA/Ca microglia consistently produced less NO than did BALB/c microglia after stimulation with LPS or with IFN-γ plus TNF-α, and they inhibited T. gondii replication significantly less than did BALB/c microglia. Cells of both strains treated with IFN-γ alone significantly inhibited uracil incorporation by T. gondii, and NG-monomethyl-l-arginine (NMMA) treatment did not reverse this effect. In cells treated with IFN-γ in combination with other inducers...

Hypoglycemia in mice injected with interferon inducers is not mediated by interferon.

Vignaux, F; Gresser, I
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /08/1981 Português
Relevância na Pesquisa
35.67%
Injection of mice with several viral and nonviral inducers of interferon resulted in a marked hypoglycemia. Interferon is not responsible for this effect since inoculation of a potent antiserum to interferon (which neutralized the endogenous interferon) did not prevent hypoglycemia and administration of potent interferon preparations did not lower blood sugar. Hypoglycemia induced by Newcastle disease virus and polyriboinosinic-polyribocytidylic acid was further exacerbated by injection of insulin.

Combined Antiviral Effects of Interferon, Adenine Arabinoside, Hypoxanthine Arabinoside, and Adenine Arabinoside-5′-Monophosphate in Human Fibroblast Cultures

Bryson, Yvonne J.; Kronenberg, L. H.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /02/1977 Português
Relevância na Pesquisa
45.6%
Adenine arabinoside and human interferon are currently being evaluated in clinical trials against herpes- and poxvirus infections. Interferon production is also a normal antiviral response. It is therefore important to examine the combined actions of interferon and antiviral arabinosides for possible synergy or antagonism. We have examined the antiviral activities of human fibroblast interferon, adenine arabinoside, hypoxanthine arabinoside, and adenine arabinoside 5′-monophosphate individually, using plaque inhibition of vaccinia and herpes simplex type 2 viruses in human skin fibroblast cultures. By combining doses of interferon and arabinosides that, acting alone, give intermediate degrees of plaque inhibition, we were able to compare the combined antiviral activity with that calculated from the activity of each inhibitor alone, assuming that the activities are statistically independent. Our results show that the plaque-inhibitory activities of interferon and the arabinosides tested are statistically independent. The results also show that the arabinosides do not destabilize the antiviral state previously induced by interferon, and that interferon pretreatment does not interfere with subsequent arabinoside action in infected cells. We have also found that arabinosides do not affect the induction of interferon synthesis by either Newcastle disease virus or double-stranded ribonucleic acid...

Effects of Oxyamylose and Polyacrylic Acid on Foot-and-Mouth Disease and Hog Cholera Virus Infections

Leunen, Joseph; Desmyter, Jan; De Somer, Pierre
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /02/1971 Português
Relevância na Pesquisa
45.56%
Two interferon-inducing polycarboxylates were tested for antiviral activity on foot-and-mouth disease (FMD) virus infections in mice, guinea pigs, and swine. Polyacrylic acid, given intraperitoneally, had a protective effect on infection by FMD virus administered in the peritoneal cavity of mice and in the foot pad of guinea pigs. Chlorite-oxidized oxyamylose (COAM) was effective in mice at a dosage of 2 mg/kg. Swine were not protected against naturally transmitted FMD by 120 mg/kg of COAM nor by polyacrylic acid. Swine were not totally unresponsive to COAM since it delayed symptoms of hog cholera. Interferon was not detected in the serum of COAM-treated swine. With FMD virus, an example was found of activity of interferon inducers in experimental hosts and lack of activity in a natural host.

Inducers of Interferon Inhibit the Mitotic Response of Liver Cells to Partial Hepatectomy

Jahiel, Rene I.; Taylor, David; Rainford, Norbert; Hirschberg, Stephen E.; Kroman, Rayna
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /04/1971 Português
Relevância na Pesquisa
35.7%
Partially hepatectomized mice were injected with inducers of interferon, and the mitotic activity of liver cells was measured. The inducers were polyriboinosinic·polyribocytidylic acid, poly(I·C), Newcastle disease virus, and statolon. Each inhibited the mitosis of liver cells. Poly(I·C) was effective in doses as low as 1 μg per mouse. Polyriboinosinic acid, poly(I), had no inhibitory effect. These results extend the spectrum of action of inducers of interferon to inhibition of mitotic division of an aneoplastic, nonaneuploid mammalian cell.

Interferon System in Cells from Human Tumors and from Persons Predisposed to Cancer

Worthington, Michael; Aaronson, Stuart A.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /03/1971 Português
Relevância na Pesquisa
45.66%
In the present study, the interferon system was evaluated in fibroblasts from persons predisposed to leukemia or other cancers, in fibroblasts from persons with neoplastic disease, and in human tumor cells. Of 31 normal fibroblast strains from patients with tumors or diseases associated with a high incidence of malignancy, only one cell strain had a poor response to either of the two interferon inducers used, polyinosinic-polycytidylic acid and Chikungunya virus. On the other hand, cell cultures of five human tumors were much less sensitive to the antiviral effect of these interferon inducers and of human interferon and produced less interferon in response to Chikungunya virus than any of the nontumor tissues studied.

Comparative Production of Interferon by Human Fetal, Neonatal, and Maternal Cells

Carter, William A.; Hande, Kenneth R.; Essien, Boniface; Prochownik, Edward; Kaback, Michael M.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /05/1971 Português
Relevância na Pesquisa
45.57%
Production of interferon was studied in fibroblasts cultured from human fetal, neonatal, and maternal tissue. Human fetal and maternal cells were paired to diminish genetic variability. Fetal cells displayed an increased response to two inducers of interferon, virus and synthetic double-stranded ribopolynucleotide. Fetal cells released 300-fold more interferon than maternal cells on exposure to poly rI:rC. This enhanced capacity for interferon production was consistent in cultures developed from fetal skin obtained between the 10th and 20th gestational week. The response was relatively stable, persisting in cells cultured for 18 generations (about 14 weeks). On infection with Newcastle disease virus, fetal cells produced, on the average, 4 to 6.5 times more interferon than maternal or neonatal cells. The virus was adsorbed with equal efficiency by each type of cell. Increased production is apparently independent of the rates of overall protein synthesis, since fetal and maternal cells have very similar rates of total protein synthesis.

Effect of Interferon and Interferon Inducers on Infections with a Nonviral Intracellular Microorganism, Rickettsia akari1

Kazar, J.; Krautwurst, P. A.; Gordon, F. B.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /06/1971 Português
Relevância na Pesquisa
65.72%
The effect of mouse interferon (IF) on the multiplication of Rickettsia akari in homologous (L-929) cell cultures and the effect of IF inducers on R. akari infection in mice were investigated. There was a reduction in the proportion of cells containing rickettsiae in IF-treated cultures and in the yield of rickettsiae from these cultures, as compared with those from infected cultures without IF. Trypsin treatment and heating for 1 hr at 65 C destroyed this antirickettsial activity of the IF preparation, whereas ultracentrifugation (105,000 × g for 90 min) and acidification at pH 2.0 did not affect it. There was no evidence that mouse IF inactivated R. akari directly, nor did it have an inhibitory effect on multiplication of R. akari in heterologous chick embryo cell or monkey kidney cell cultures. Susceptibility of R. akari to the action of IF was about 16 times less than that of Chlamydia trachomatis and 256 times less than the susceptibility of vesicular stomatitis virus. Mice were not protected from infection with R. akari by intraperitoneal injection with IF inducers, Newcastle disease virus (108.3 plaque-forming units/0.2 ml) or polyriboinosinic acid-polyribocytidylic acid complex (poly I:C, 200 μg/0.2 ml), within 24 hr before or 24 hr after intraperitoneal challenge. The yields of R. akari harvested from the spleens...

Effect of Interferon and Interferon Inducers on Infections with a Nonviral Intracellular Microorganism, Chlamydia trachomatis1

Kazar, J.; Gillmore, J. D.; Gordon, F. B.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /06/1971 Português
Relevância na Pesquisa
65.66%
The effect of mouse interferon (IF) on the multiplication of Chlamydia trachomatis (strain MRC-1/G) in homologous (L-929) cell cultures and the effect of the IF inducers Newcastle disease virus (NDV) and polyriboinosinic acid-polyribocytidylic acid complex (poly I:C) on the experimental infection of mice with aerosolized C. trachomatis (strain MoPn) were investigated. Treatment of infected cell cultures with IF reduced the number of cells containing chlamydial inclusions and depressed the yield of chlamydiae as determined by titrations for infectivity. Growth of chlamydiae was reduced when cultures were exposed to IF 6 or 18 hr before infection, and slight reduction of the yield was also detectable in cell cultures treated with IF at early intervals (0 or 4 hr) after chlamydial infection. No effect of IF on penetration of chlamydiae into mouse cells was observed, whether phagocytic cells from peritoneal washings or L-929 cells were used, indicating that the inhibitory effect of IF occurs after chlamydiae enter the host cell. Additional evidence was obtained that a significant effect of IF occurs at an early stage in maturation of the intracellular chlamydiae. In mice exposed repeatedly to NDV aerosols and challenged with aerosolized MoPn 8 hr after the first exposure to NDV...

Hyporeactivity of Infection: Potential Limitation to Therapeutic Use of Interferon-Inducing Agents

Stringfellow, D. A.; Glasgow, L. A.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /11/1972 Português
Relevância na Pesquisa
45.57%
Interferon inducers are generally most effective as antiviral agents when used prophylactically. One possible explanation for this is that animals develop a state of hyporeactivity during the course of a virus infection. Such a progressive loss of capacity to produce interferon was observed with a representative group of interferon-inducing agents (polyinosinic-cytidylic acid, Tilorone hydrochloride, New-castle disease virus, or a strain of encephalomyocarditis virus) during the course of a model picornavirus infection in mice.

Natural killer cell in systemic lupus erythematosus. Defects in effector lytic activity and response to interferon and interferon inducers.

Sibbitt, W L; Mathews, P M; Bankhurst, A D
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /05/1983 Português
Relevância na Pesquisa
55.66%
Spontaneous cytotoxicity mediated by natural killer (NK) cells is impaired in several human diseases including systemic lupus erythematosus (SLE). The precise mechanism(s) by which NK activity is suppressed in patients with SLE is generally unknown. The present study was designed to focus on cellular defects per se in NK cells from patients with SLE. It was observed that the usual enhancing effect of interferon (IF) and IF inducers was markedly impaired in SLE patients. Of 24 SLE patients studied, 17 had significantly decreased NK activity relative to controls. NK activity had a significant negative correlation with clinical activity score (r = -0.56, P less than 0.005) but was not correlated with corticosteroid dose, antinuclear antibody titers, total hemolytic complement (CH50), or sedimentation rate. Furthermore, significant depressions in NK activity correlated with variations in disease activity in six patients followed serially. Depressed NK function could not be reversed by prolonged in vitro incubation at 37 degrees C or with protease treatment. Furthermore, depressed NK activity was not altered by removal of glass adherent cells nor was a suppression of NK activity in normal controls seen by the addition of SLE peripheral mononuclear cells. No reversal of depressed activity to normal levels was seen by the addition of indomethacin nor did the supernatants from SLE cell cultures cause a suppression of normal NK function. NK activity in SLE patients did not respond normally to IF inducers (poly-I:C and concanavalin A) even if the SLE patients had normal NK function. The response of SLE cells to exogenous IF was also impaired. The number of effector-target conjugates was quantitated with several target cells (K562...

Effect of Antiviral Agents in Equine Abortion Virus-Infected Hamsters1

Lieberman, Melvin; Pascale, Andrea; Schafer, Thomas W.; Came, Paul E.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /02/1972 Português
Relevância na Pesquisa
35.7%
Equine abortion virus, a member of the herpesvirus group, produces a lethal infection in hamsters. With this system, the protective effect of certain inhibitors of deoxyribonucleic acid viruses, inducers of interferon and exogenous interferon, was evaluated. Of the various agents studied, 9-β-d-arabinofuranosyladenine markedly suppressed mortality, and 5-iodo-2′-deoxyuridine, distamycin A, and N-ethylisatin β-thiosemicarbazone were inactive. Of the inducers tested, statolon, ultraviolet-irradiated Newcastle disease virus, and polyriboinosinic:polyribocytidylic acid (poly I:C) were protective, and endotoxin, polyacrylic acid, and polymethacrylic acid did not protect. Administration of exogenous interferon did not afford protection. Statolon and ultraviolet-irradiated Newcastle disease virus induced circulating interferon in hamsters, whereas poly I:C, endotoxin, and polyacrylic acid did not produce interferon. Because of the severity of the disease produced in hamsters by equine abortion virus, lack of protective activity by an agent in this system should not preclude possible efficacy against other members of the herpesvirus group.

Deoxycytidyl-Deoxyguanosine Oligonucleotide Classes A, B, and C Induce Distinct Cytokine Gene Expression Patterns in Rhesus Monkey Peripheral Blood Mononuclear Cells and Distinct Alpha Interferon Responses in TLR9-Expressing Rhesus Monkey Plasmacytoid Dendritic Cells

Abel, Kristina; Wang, Yichuan; Fritts, Linda; Sanchez, Eleonora; Chung, Eugene; Fitzgerald-Bocarsly, Patricia; Krieg, Arthur M.; Miller, Christopher J.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /05/2005 Português
Relevância na Pesquisa
35.7%
To determine if deoxycytidyl-deoxyguanosine oligonucleotides (CpG ODN) can be used effectively as nonspecific inducers of innate immune defenses for preventative or therapeutic interventions in infectious disease models for nonhuman primates, the present study evaluated the response of rhesus monkey peripheral blood mononuclear cells to three different synthetic CpG ODN classes by defining the cytokine gene expression patterns and by characterizing IFN-α/β responses. Depending on the type and dose of CpG ODN used for stimulation, distinct gene expression patterns were induced. CpG ODN class A (CpG-A ODN) and CpG-C ODN, but not CpG-B ODN, were potent inducers of alpha interferon (IFN-α), and this response was due to IFN-α production by TLR9-positive plasmacytoid dendritic cells. Importantly, there was a dose-dependent increase in IFN-α responses to CpG-A ODN but a dose-dependent decrease in IFN-α responses by CpG-B ODN. The most sustained IFN-α response was induced by CpG-A ODN and was associated with a stronger induction of interferon regulatory factor 7 and the induction of several interferon-stimulated genes. In contrast, and independent of the dose, CpG-B ODN were the weakest inducers of IFN-α but the most potent inducers of proinflammatory cytokines. CpG-C ODN induced cytokine gene expression patterns that were intermediate between those of CpG-A and CpG-B ODN. Thus...

Interrelationships of Interferon and Immunity During Viral Infections

Glasgow, Lowell A.
Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 01/07/1970 Português
Relevância na Pesquisa
45.58%
Interferon is one determinant of host resistance. The immune responses, cellular or humoral, are other components. Cell-mediated responses appear to be involved in host resistance to certain viral infections, particularly the herpesvirus group and vaccinia virus. It is suggested that immune and interferon responses may complement one another and contribute to host resistance. The relative importance of each component depends upon the virus-host interaction. Finally, evidence has been presented which suggests that production of interferon as a result of antigen-sensitized cell interaction may further link these two components of the host response.

Interferon and Interferon Inducers in the Treatment of Malignancies

Levy, Hilton B.; Riley, Freddie; Margolis, Sam
Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 01/07/1970 Português
Relevância na Pesquisa
75.66%
The mechanism of the antitumor action of polyinosinic-polycytidylic acid is probably multifaceted. The compound induces the synthesis of interferon, and interferon probably is active against some tumors. Poly I:poly C alters protein and RNA synthesis in tissue culture. It specifically inhibits such macromolecule synthesis in tumors in vivo, while having less inhibitory action on synthesis in normal organs, or it may actually enhance. Finally, poly I:poly C strongly enhances graft vs. host rejection mechanisms, which may play a role in the rejection of some tumors.

Interferon and Interferon Inducers in Protozoal Infections

Jahiel, Rene I.
Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 01/07/1970 Português
Relevância na Pesquisa
75.83%
Several interferon inducers (Newcastle disease virus, statolon, and poly rI:poly rC) as well as exogenous mouse interferon protect mice from sporozoite-induced Plasmodium berghei malaria, as long as they are administered before the end of the preerythrocytic phase of development of the parasite. The protective effect of the interferon inducers was related to their interferon-inducing effect; the protective effect of the interferon preparations was related to the interferon titer of the preparations, and it exhibited other attributes of interferon such as species specificity. In contrast to sporozoite-induced infection, blood forms-induced P. berghei malaria was only weakly susceptible to the protective effect of interferon inducers. This difference may provide an approach to study the mechanism of protection. The growth in cell cultures of another intracellular protozoon, Toxoplasma gondii, is also inhibited by interferon (22). The fact that P. berghei and T. gondii (as well as another group of intracellular parasites susceptible to interferon, the Chlamydia) have their own ribosomes raises questions, concerning the role of host cell ribosomes in the host cell-parasite relationship of these intracellular parasites and in the mechanism of interferon action against them...

Circulating Interferon Production in the Mouse : Origin and nature of cells involved and influence of animal genotype

De Maeyer, Edward; De Maeyer-Guignard, Jaqueline; Jullien, Pierre
Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 01/07/1970 Português
Relevância na Pesquisa
45.68%
A radiobiological study of circulating interferon production in the mouse was undertaken in the hope of elucidating the site(s) of circulating interferon production. After total body X-irradiation of the animals, different radiosensitivities of circulating interferon production were observed with different viral inducers. Myxovirus-induced circulating interferon production was especially radiosensitive. Moreover, a study of interferon production in syngeneic and xenogeneic radiochimeras demonstrated that cells producing NDV (Newcastle disease virus)-induced circulating interferon were derived from hematopoietic stem cells. In addition, treatment of mice with antilymphocyte serum significantly reduced NDV- and Sendai virus-induced circulating interferon, as opposed to other inducers. Taken together, these results strongly suggest that the lymphocyte is the major source of myxovirus-induced circulating interferon. A survey of interferon production in 12 inbred mouse strains, using NDV as inducer, revealed the existence of low and high producers. A Mendelian analysis carried out with low producing Balb/c and high producing C57BL indicated that the difference between low and high interferon producers was caused by a single, autosomal, codominant factor.

The Defensive Role of the Interferon System

Baron, Samuel
Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 01/07/1970 Português
Relevância na Pesquisa
85.6%
The evidence relating the interferon system to the infectious process has been examined. The available evidence supports the view that the interferon system is an important component of the body's nonimmune defenses, which are probably the major causes of recovery from already established virus infections of body tissues. The interferon system can also serve to limit virus spread through the bloodstream. Factors which may influence the interferon system and thereby influence virus infection have been considered. Finally, evidence is presented which indicates that the interferon system is one of the determinants of virulence of certain viruses and is one of the determinants of some persistent virus infections.

Spontaneous release of interferon gamma by intestinal lamina propria lymphocytes in Crohn's disease. Kinetics of in vitro response to interferon gamma inducers.

Fais, S; Capobianchi, M R; Pallone, F; Di Marco, P; Boirivant, M; Dianzani, F; Torsoli, A
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /04/1991 Português
Relevância na Pesquisa
35.7%
The spontaneous induced release of interferon gamma (IFN gamma) by cultured intestinal lamina propria lymphocytes was investigated in patients with Crohn's disease. In contrast to normal lymphocytes, intestinal lymphocytes from these patients spontaneously released IFN gamma and seemed to contain IFN gamma in their cytoplasm. Autologous peripheral lymphocytes did not release IFN gamma. When stimulated with interferon inducers lamina propria lymphocytes from Crohn's disease tissue showed an increase in IFN gamma release 24 hours after induction with no appreciable further increase over the next two days of culture, while in control cells, either peripheral or intestinal, IFN gamma release progressively increased, peaking 72 hours after induction. These findings indicate that in Crohn's disease the intestinal lymphocytes are stimulated in vivo to produce IFN gamma and that the spontaneous IFN gamma production is compartmentalised to the gut lymphocytes. These data support the concept that locally released IFN gamma has a crucial role in cell interactions in the lamina propria and contribute to the locally occurring immune phenomena in Crohn's disease, including the increased epithelial expression of major histocompatibility complex class II antigens.

Target-Organ Treatment of Neurotropic Virus Disease with Interferon Inducers

Allen, Lois B.; Cochran, Kenneth W.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /11/1972 Português
Relevância na Pesquisa
35.69%
Interferon inducers were used against vaccinial encephalitis to study the target-organ treatment of neurotropic disease and to correlate interferon levels and the antiviral state following such treatment. A 45-μg amount of statolon, 30 μg of polyribinosinic-polyribocytidylic acid complex (poly I·poly C), or 0.0154 HA unit of Sendai virus given intracerebrally protected 100% of mice challenged the next day with 1,000 median lethal doses (LD50) of vaccinia virus. Significant protection against 1,000 LD50 of vaccinia virus persisted for 1, 4, or 3 weeks after poly I·poly C, statolon, or Sendai virus (154 HA units), respectively. These doses of poly I·poly C and statolon were also used to study postinfection treatment. Mice challenged with 1, 10, 100, or 1,000 LD50 were treated intracerebrally with poly I·poly C or statolon 24 or 48 hr later. Significant increases in survival time were seen in mice challenged with 1 to 100 LD50 of vaccinia virus and treated 24 hr later. At challenges of 10 or 100 LD50, statolon was more effective than poly I·poly C in increasing survival times. When treatment was delayed until 48 hr after infection, significant increases in survival time occurred only when the challenges were in the range of 1 to 10 LD50...