Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0009450 (infectious diseases)
83,438 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunosuppression as a consequence of acute and chronic stress can increase the susceptibility of cattle to a range of infectious diseases. In order to develop a panel of immune function assays for investigating the effects of potential stressors on immune competence in cattle, the effect of treatment with short- and long-acting preparations of the synthetic glucocorticoid dexamethasone was examined. Short-acting dexamethasone (dexamethasone sodium phosphate 0.08 mg/kg) followed 37 h later by long-acting dexamethasone (dexamethasone-21 isonicotinate 0.25 mg/kg) was injected intramuscularly and blood was collected to assess immune functions at intervals over the subsequent 11 days from 6 treated and 6 control Hereford steers. Dexamethasone induced leukocytosis (neutrophilia, eosinopenia, lymphopenia, monocytosis), an increased neutrophil:lymphocyte ratio, an elevated percentage of CD4+ lymphocytes, a decreased total CD8+ lymphocyte count, decreased total and percentage WC1+ lymphocytes, an elevated percentage of IL-2 receptor alpha (IL-2Ralpha)+ lymphocytes, and an elevated percentage of B lymphocytes. In vitro chemotaxis of peripheral blood neutrophils to human C5a and ovine IL-8 was increased by dexamethasone treatment. Lymphocyte proliferation in the presence of phytohaemagglutinin, and serum concentrations of IgM, but not IgA or IgG1, were suppressed by dexamethasone treatment, whereas mitogen-induced production of interferon-gamma (IFN-gamma), neutrophil expression of CD18, neutrophil myeloperoxidase activity and natural killer (NK) cell activity were not influenced by dexamethasone treatment. The results indicate the potential for haematology and immune function assays to reflect elevated activity of the hypothalamic-pituitary-adrenocortical axis in cattle. Immunological parameters may thus provide a useful adjunct to cortisol and behavioural observations for assessing the impact of stress on the welfare of cattle.
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PMID:The effect of dexamethasone on some immunological parameters in cattle. 1059 72

Interleukin-12 (IL-12) has been shown to possess potent immunoregulatory and antitumoral effects. We have evaluated the anti-oncogenic potential and the mechanisms of the antitumoral effect of in vivo adenovirus-mediated transfer of IL-12 gene in a murine model of colon cancer. AdCMVIL-12 was constructed to permit coordinated production of p40 and p35 subunits of IL-12 gene to obtain the maximum IL-12 bioactivity. Infection of murine colon cancer CT-26 cells in vitro with AdCMVIL-12 resulted in the production of high levels of IL-12. In vivo gene therapy of colon cancer nodules by intratumoral injection of AdCMVIL-12 induced a local increase in IL-12 and interferon-gamma levels and a complete regression of the tumor in 26 of 34 (76%) mice. Tumor disappeared between days 7 and 10 after vector administration. The antitumoral effect was mediated by CD8+ T cells and was associated with the generation of cytotoxic T lymphocytes against colon cancer cells. Animals that eliminated the tumor were protected against a second administration of neoplastic cells. Treatment with AdCMVIL-12 of one tumor nodule also caused regression of established tumors at distant sites. These data demonstrate that AdCMVIL-12 is a useful therapeutic tool for established colon cancer in mice and should be considered for application in humans.
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PMID:Regression of colon cancer and induction of antitumor immunity by intratumoral injection of adenovirus expressing interleukin-12. 1060 48

We have previously observed that aged lupus-prone (NZB/NZW)Fl (BWF1) mice when infected with Plasmodium chabaudi show an improvement in their clinical lupus-like symptoms. In order to study the mechanisms involved in the long-lasting protective effect of the P. chabaudi infection in lupus-prone mice we analysed specific aspects of the cellular response, namely the profiles of cytokine mRNA expression and cytokine secretion levels in old BWF1 mice, in comparison with uninfected age-matched BWF1 mice and infected or uninfected BALB/c mice. Two months after infection, cells from BWF1 mice were stimulated with concanavalin A (Con A) and demonstrated a recovery of T cell responsiveness that reached the levels obtained with BALB/c cells. Old BWF1 mice showed high levels of interferon-gamma (IFN-gamma) and IL-5 production and correspondingly low levels of IL-2 and IL-4 secretion before infection with P. chabaudi. Infection did not modify the IFN-gamma levels of BWF1 T cells, whereas it considerably increased the secretion of the Th2-related cytokines IL-4, IL-5 and IL-10. In addition, only BWF1 T cells showed increased mRNA expression of tumour necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta). This counter-regulatory cytokine network of infected BWF1 mice may be involved in the improvement of their lupus symptoms. The results of our investigations using the complex model of P. chabaudi infection can be extended and, by using more restricted approaches, it may be possible to explain the multiple regulatory defects of lupus-prone mice.
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PMID:Changes in the cytokine profile of lupus-prone mice (NZB/NZW)F1 induced by Plasmodium chabaudi and their implications in the reversal of clinical symptoms. 1063 72

The CD14 molecule, which is known to be a receptor for endotoxin, is expressed on monocytes and neutrophils. It is found as a soluble CD14 (sCD14) in circulation, and the plasma level has been shown to be increased in some infectious diseases, including sepsis. To investigate the potential significance of circulating sCD14 in Kawasaki disease (KD), the plasma level of sCD14 was measured using ELISA in patients with KD, patients with a Gram-negative bacterial infection (GNBI) including sepsis, patients with viral infection (VI), and healthy controls. We also analysed CD14 receptor expression in monocytes and neutrophils using flow cytometry and a semiquantitative reverse transcription-polymerase chain reaction. Although KD patients had significantly lower counts of peripheral neutrophils and monocytes than GNBI patients, KD patients had significantly higher levels of sCD14 than GNBI. No significant correlations were observed between sCD14 levels and clinical laboratory values or the cytokine (interferon-gamma, tumour necrosis factor-alpha) levels in the acute phase. The mean intensity of CD14 receptor expression on neutrophils markedly increased in the acute phases of KD and GNBI compared with that in their convalescent phases, while that on monocytes decreased. The expression of CD14 mRNA in neutrophils increased in the acute phases of KD and GNBI, while that in monocytes did not decrease but instead remained quite abundant. The present findings suggest that the elevated level of circulating sCD14 appears to be an important parameter for KD and that sCD14 shedding is accompanied by different kinetics regarding the expression of CD14 antigen and CD14 gene between monocytes and neutrophils.
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PMID:Increased levels of circulating soluble CD14 in Kawasaki disease. 1063 78

Differences in the immune response between 2 strains of interferon-gamma knockout mice (BALB/c-GKO and C57BL/6-GKO) infected with Cryptosporidium parvum were examined because the course of infection among these 2 strains is markedly different. Infection of the BALB/c-GKO with C. parvum (2 X 10(6) oocysts/mouse) resulted in slight weight loss, oocyst shedding, and recovery from infection by 2 wk postinfection (PI). Infection with 100 oocysts in the C57BL/6-GKO mice resulted in significant weight loss, oocyst shedding, and death by day 10 PI. Splenocytes from infected mice were able to proliferate in a dose-dependent manner to soluble C. parvum-sporozoite antigen (SAg). In vitro stimulation with SAg resulted in an increase in interleukin (IL)-2, IL-4, IL-5, and tumor necrosis factor-alpha mRNA cytokine expression from splenocytes of infected BALB/cGKO mice. In contrast, only IL-5 mRNA expression was increased in the splenocytes from C. parvum-infected C57BL/6-GKO mice. Phenotypic analysis indicated no significant differences in the splenic cell populations. Previous studies indicated that susceptibility to C. parvum is dependent on CD4+ T cells and interferon-gamma production. The present study indicates that although both of these strains of knockout mice become infected with C. parvum, resolution of infection may be in part dependent on the expression of Th2 cytokines.
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PMID:Cytokine expression and specific lymphocyte proliferation in two strains of Cryptosporidium parvum-infected gamma-interferon knockout mice. 1078 May 49

An interleukin-12 (IL-12) expression plasmid was transferred, using a gene gun, to mice infected with Leishmania major or Trypanosoma cruzi. Transfer of the IL-12 gene to susceptible BALB/c mice resulted in regression of lesion size and reduced the number of parasites in draining lymph nodes (LN) at the site of L. major infection. Coincident with these protective effects, the T-helper type (Th) response shifted towards Th1, as evaluated by cytokine production in vitro and L. major-specific antibody responses. Protective effects of the IL-12 gene were also observed in T. cruzi infection. Treatment of BALB/c mice infected with T. cruzi enhanced the production of interferon-gamma (IFN-gamma) by spleen cells, while suppressed production of interleukin-10 (IL-10) compared with control mice. Administration of anti-CD4 or anti-CD8 monoclonal antibody (mAb) abolished the protective immunity against T. cruzi infection, and treatment with the IL-12 gene could not restore the resistance in these mice. Mice depleted of natural killer (NK) cells with anti-asialo GM1 also became susceptible to infection, while the resistance was restored when these mice were treated with the IL-12 gene. Thus, target cells for the treatment appear to be CD4+ and CD8+ T cells, which are ordinarily activated by NK cells. These results suggest that the transfer of cytokine genes using a gene gun is an effective method for investigating the roles of cytokines and gene therapy in infectious diseases.
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PMID:Gene gun-mediated delivery of an interleukin-12 expression plasmid protects against infections with the intracellular protozoan parasites Leishmania major and Trypanosoma cruzi in mice. 1079 10

From a series of preclinical studies and animal experiments, we have been able to demonstrate that DNA vaccines are a promising tool in strategies for protecting hosts from a variety of infectious diseases. Since the promoter activity of the human cytomegalovirus immediate-early promoter/ enhancer (CMV promoter) is known to be responsive to an elevation in the level of intracellular cAMP, we hypothesized that use of cAMP analogue (8-Bromo adenosine 3'5'-cyclic monophosphate, 8 Br-cAMP) would increase the level of transgene expression supported by the CMV, and enhance the ability of DNA vaccines to evoke an immune response against the transgene product in vivo. To evaluate this hypothesis, immune responses against HIV-1 envelope protein, gp160, an immunogenic HIV-1 component expressed under the control of the CMV promoter, were evaluated in BALB/c mice with or without stimulation by 8 Br-cAMP. DNA vaccine with 8 Br-cAMP was intramuscularly (i.m.) or intranasally (i.n.) administered to BALB/c mice twice on days 0 and 14. Regardless of which route was used, the combination increased the serum IgG antibody (Ab) titer, HIV-1-specific cytotoxic T lymphocyte (CTL) activity and the delayed-type hypersensitivity (DTH) response, compared with the effect of using the vaccine alone. When administered via the i.n. route, the combination also remarkably increased the titer of secretory IgA (sIgA). Moreover, it induced increased production of interferon-gamma with reduction in IL-4 synthesis, and decreased the ratio of serum IgG1/IgG2a. However, these enhancements were not observed when 8 Br-cAMP was coadministered with peptide vaccine or protein antigen. These data suggest that 8 Br-cAMP is able to enhance both humoral and cellular immune responses induced by the DNA vaccine. The induction of T helper type 1 (Th1) immunity against HIV-1 was also enhanced by coadministration of 8 Br-cAMP. A CAT assay study demonstrated that the adjuvant effect of 8 Br-cAMP may be due to the activation of the CMV promoter in the DNA vaccine. The virus challenge experiment in a mouse influenza model also proved our hypothesis.
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PMID:8 Br-cAMP enhances both humoral and cell-mediated immune responses induced by an HIV-1 DNA vaccine. 1080 93

The role of cytokines in the pathogenesis and immunity of Marek's disease (MD), a herpesvirus-induced T-cell lymphoma in chickens, is poorly understood. Two different experiments were used to examine the potential role of particular cytokines in the pathogenesis and immune responses of MD. First, chicken embryo fibroblasts (CEF) were stimulated with lipopolysaccharide (LPS) and/or recombinant chicken interferon-gamma (rChIFN-gamma) and used to develop techniques for examining transcription of IFN-alpha, IFN-gamma, inducible nitric oxide synthase (iNOS), interleukin (IL)-1beta, IL-2, IL-6 and IL-8 by reverse transcription-polymerase chain reaction (RT-PCR). Addition of LPS and/or rChIFN-gamma resulted in the up-regulation of mRNA for iNOS, IL-1beta and IL-6, while IFN-gamma was up-regulated by LPS alone. IL-2 was down-regulated by the treatments. Second, to determine the effects of Marek's disease herpesvirus (MDV) infection on cytokine transcription in vivo, chickens were infected with MDV at 21 days of age and examined at 7 days post-infection (p.i.) (exp. 1) or were infected with MDV at 1 day of age and examined from 3 to 15 days p.i. (exp. 2). In MDV-infected chickens, IFN-gamma transcription was up-regulated as early as 3 days p.i. until the termination of the experiment at 15 days p.i., while iNOS and IL-1beta were up-regulated between 6 and 15 days p.i. Infection of 1-day-old chicks increased levels of mRNA for IFN-gamma and iNOS between 16- and 64-fold at 9 days p.i. These results suggest that IFN-gamma and iNOS may play an important role in the pathogenesis of MD.
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PMID:Expression of cytokine genes in Marek's disease virus-infected chickens and chicken embryo fibroblast cultures. 1080 61

We report a rare case of a male patient without known immunodeficiency consecutively diagnosed with visceral leishmaniasis, brain abscess and cavitating pneumonia in the 3rd decade of life. Chronic granulomatous disease (CGD) was diagnosed by a nitroblue tetrazolium test. A p47-phox mutation of the NADPH oxidase of the leukocytes was suspected by immunoblotting and confirmed by DNA analysis. The patient was homozygous for this mutation while his mother and sister were heterozygous asymptomatic carriers. After the CGD diagnosis the patient started a chronic prophylactic regimen with subcutaneous interferon-gamma (0.05 mg/m2 of body surface/three times a week), and oral trimethoprim-sulfamethoxazole and itraconazole (both at 5 mg/kg/day) with no subsequent infections after 12 months of follow-up.
Infection
PMID:Visceral leishmaniasis and other severe infections in an adult patient with p47-phox-deficient chronic granulomatous disease. 1087 44

Individual and combined effects of several isomers of retinoic acid (RA) and 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) on interferon-gamma (IFN-gamma) secretion by blood mononuclear leukocytes (MNL) from nulliparous and postparturient Holstein cattle were evaluated in vitro. In the first experiment, effects on incubation period (24 to 72 hours) and time of supplementation (0 to 32 hours) with all-trans, 9-cis, 13-cis-, and 9,13-dicis-RAs (0 to 100 nM) on IFN-gamma secretion by pokeweed mitogen (PWM)-stimulated (0 and 10 micrograms/ml) MNL from nulliparous cattle were evaluated. In the second experiment, MNL from postparturient cows (bled at 0, 2, 4, and 16 days postpartum) were stimulated with PWM (0 and 10 micrograms/ml) in the presence of RA isomers (9-cis- or 9,13-dicis-RA; 0 to 100 nM), 1,25-(OH)2D3 (0 to 100 nM), or with combinations of these metabolites. The results show that individual isomers of RA had no effect on IFN-gamma secretion by PWM-stimulated MNL from nulliparous or postparturient cows. Furthermore 1,25-dihydroxyvitamin D3 inhibited IFN-gamma secretion by MNL from nulliparous and postparturient dairy cows; however, the degree of inhibition was greater when 9-cis- and 9,13-dicis-RA were also present in the cultures. Finally mononuclear leukocytes from postparturient dairy cows produced substantially less IFN-gamma than did MNL from nulliparous cattle. It is concluded that retinoic acids individually did not affect the capacity of leukocytes from dairy cattle to secrete IFN-gamma. This result is in marked contrast to studies in monogastric species indicating that RAs inhibit IFN-gamma secretion by peripheral blood T cells. Inhibition of IFN-gamma secretion by 1,25-(OH)2D3 was potentiated by 9-cis- and 9,13-di-cis-retinoics acids, suggesting that an excess of dietary vitamins A and D may compromise further the naturally immunosuppressed postparturient dairy cow. Additional research is necessary to determine if the combined effects of these metabolites on IFN-gamma secretion represent an increased susceptibility of the dairy cow to infectious diseases during the periparturient period. Lower secretion of IFN-gamma by MNL from postpartutient dairy cows, relative to nulliparous cattle, suggests that recently-calved cows are naturally immunosuppressed.
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PMID:Effects of retinoic acid and 1,25-dihydroxyvitamin D3 on IFN-gamma secretion by mononuclear leukocytes from nulliparous and postparturient dairy cattle. 1088 2


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