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141.
Reactive oxygen species (ROS), represented by superoxide, hydrogen peroxide and hydroxyl radicals, have been implicated in many diseases including cancer. ROS have been known to play an important role in the initiation and promotion of multistep carcinogenesis. The cellular antioxidants play a crucial role in protection against neoplastic disease. However, very little is known about the antioxidant defense in cervical carcinoma. This is addressed in the present study. Lipid peroxides, glutathione content and the activities of antioxidant enzymes, together with vitamin C and E content, were estimated in patients who had carcinoma of the cervix, and the values were compared with those of normal women. The results showed a remarkable reduction in the content of glutathione, vitamin E and C. Activities of glutathione peroxidase and superoxide dismutase were also reduced in cervical cancer compared to normal controls (P < 0.001). This reduction was more marked in late stages (III, IV) than in early stages (I, II) (P < 0.001). Glutathione was reduced more in poorly differentiated tumors (grade III) than in well and moderately differentiated ones (grade I, II) (P < 0.05). Levels of lipid peroxides were found to be significantly higher in malignant than in normal tissue samples and their levels were correlated with advanced clinical stage (P < 0.001). Our results suggest impaired antioxidant status in carcinoma of the cervix. This impairment is related to tumor progression. 相似文献
142.
Khaliq A Dunk C Jiang J Shams M Li XF Acevedo C Weich H Whittle M Ahmed A 《Laboratory investigation; a journal of technical methods and pathology》1999,79(2):151-170
Early placental development occurs in an environment of relative hypoxia. Hypoxia promotes angiogenesis and up-regulates vascular endothelial growth factor (VEGF) expression while it down-regulates placenta growth factor (PIGF) that possess 53% homology with VEGF. Morphological studies show poor placental vascular development and an increase in the mitotic index of cytotrophoblasts in intrauterine growth restriction (IUGR). We hypothesized that the reported relatively high oxygen level in the intervillous space in contact with IUGR placental villi will limit angiogenesis by changes in VEGF and PIGF expression and function. Western immunoblot analysis demonstrates a diametric expression of PIGF and VEGF proteins throughout pregnancy with PIGF levels increasing and VEGF levels decreasing, consistent with placental oxygenation. In IUGR placentae, the ratio of PIGF/GAPDH mRNA was increased by 2.3-fold (p < 0.03) and PIGF protein levels were also increased, (p < 0.05) as compared with gestationally-matched normal placentae. PIGF mRNA and protein were localized to the trophoblast bilayer and villous mesenchyme of the human placenta throughout gestation. In vitro studies demonstrated that increasing oxygen tension (hyperoxia) up-regulated PIGF protein in term placental villous explants, whereas hypoxic culture of a term trophoblast choriocarcinoma cell line (BeWo) down-regulated PIGF mRNA and protein and VEGFR-1 (Flt-1) autophosphorylation. The addition of PIGF-1 to a spontaneously transformed first trimester cytotrophoblast cell line stimulated DNA synthesis while PIGF-2 had little effect. VEGF and PIGF exert their biological actions by means of a common receptor VEGFR-1. In the first trimester trophoblast cells, PIGF-1 increased the association of phosphorylated extracellular signal-related kinase (ERK) with VEGFR-1 immunoprecipitates while both PIGF-1 and PIGF-2 also potentiated endogenous VEGF mediated association of phosphorylated extracellular related kinase (ERK) with VEGFR-2 (KDR). More importantly, the addition of PIGF-1 had little effect while PIGF-2 inhibited cell growth in cultured endothelial cells derived from human umbilical vein. Nitric oxide (NO) is reported to promote angiogenesis and PIGF-2 inhibited the basal release of NO from the first trimester trophoblast. The tissue expression and functional studies support the hypothesis of "placental hyperoxia" in early-onset IUGR because hypoxia down-regulates trophoblast PIGF levels, PIGF expression is increased in IUGR, and PIGF-2 inhibits endothelial cell growth. Taken together, these changes provide a cellular explanation for the observed poor angiogenesis in the pathogenesis of IUGR and show that the two PIGF isoforms may modulate trophoblast and endothelial cell function differently, possibly through potentiation of VEGF mediated activation of VEGF-2. 相似文献
143.
Chromosomal aberrations and micronucleus frequency in nurses occupationally exposed to cytotoxic drugs 总被引:4,自引:1,他引:4
Anwar Wagida A.; Salama Somaia I.; Serafy Mostafa M.EI; Hemida Samia A.; Hafez Ahmed S. 《Mutagenesis》1994,9(4):315-317
In this study, we evaluated the effect of low level occupationalexposure of nurses in a medical oncology unit in Cairo, Egypt,to anticancer drugs. Twenty nurses who constantly handled thesedrugs and 20 controls, matched according to age and sex, wereexamined. Metaphase chromosomes were studied. Percentages ofmetaphases with chromosomal aberrations were significantly higher(P < 0.001) in the exposed group (6.1 ± 2.7) versusthe controls (2.6 ± 1.6). The detected chromosomal aberrationswere in the form of chromatid gaps, chromatid breaks and acentricfragments. Micronucleated peripheral blood lymphocytes werealso analyzed in cytochalasin B treated binucleated lymphocytes.There was significant increase in cells with micronuclei (P< 0.001) in nurses (10.05 ± 4.71) in comparison tothe matched control (5.42 ± 2.22) (P < 0.001). Nursesexposed to the cytotoxic drugs for 相似文献
144.
145.
Role of NK cells and gamma interferon in transplacental passage of Toxoplasma gondii in a mouse model of primary infection 总被引:7,自引:0,他引:7
Abou-Bacar A Pfaff AW Georges S Letscher-Bru V Filisetti D Villard O Antoni E Klein JP Candolfi E 《Infection and immunity》2004,72(3):1397-1401
Protective immunity in mice infected with Toxoplasma gondii is mainly mediated by NK cells, CD4 and CD8 T cells, and type 1 cytokines, such as gamma interferon (IFN-gamma). To clarify the roles of NK cells and IFN-gamma in protection against primary congenital toxoplasmosis, we used recombination activating gene 2 knockout (RAG-2(-/-)) mice, which lack T and B lymphocytes, in comparison with the wild-type BALB/c model. RAG-2(-/-) mice had a significantly lower risk of fetal toxoplasmosis than BALB/c mice (25 versus 63.9%; P = 0.003). This protection was associated with an increased number of maternal NK cells, IFN-gamma secretion by spleen cells, and decreased parasitemia. In the RAG-2(-/-) mice, NK cell depletion increased both the rate of fetal infection, to 56.5% (P = 0.02), and the blood parasite burden. Conversely, in the BALB/c mice, this treatment did not modify maternofetal transmission or the blood parasite burden. Neutralization of IFN-gamma in both infected RAG-2(-/-) and BALB/c mice decreased congenital Toxoplasma transmission, contrasting with an exacerbation of maternal infection. These data suggest that a partially protective immunity against congenital toxoplasmosis is achieved due to the increased number of NK cells in RAG-2(-/-) mice. However, it seems that IFN-gamma enhances, directly or indirectly, the transplacental transmission. 相似文献
146.
J. S. Ahmed P. Wiegers S. Steuber E. Schein R. O. Williams D. Dobbelaere 《Parasitology research》1993,79(3):178-182
Theileria annulata andT. parva-infected lymphoblastoid cells were examined for their capacity to produce interferon (IFN). Supernatants of such cells were tested in biological assay for their antiviral activity. OnlyT. parva-infected cells of T-cell origin were capable of producing IFN-gamma. Supernatants of some but not allT. annulata-infected cells showed also antiviral activity, which was greatly reduced after exposure to a pH of 2. Northern-blot analysis of the cells using an IFN-gamma cDNA probe confirmed the results obtained forT. parva-infected cells in a biological assay. No IFN-gamma mRNA was detected inT. annulata-infected cells. The importance of IFN for the pathogenesis of theileriosis is discussed. 相似文献
147.
Mucous membrane pemphigoid (MMP) is an autoimmune mucocutaneous blistering disease characterized by autoantibodies to components within the basement membrane zone. In this study, we report the titers of autoantibodies to antigens in the BMZ, in the sera of 13 patients, treated with intravenous immunoglobulin as monotherapy over a consecutive 18-month period. Using bovine gingiva lysate as substrate in an immunoblot assay, autoantibodies to human bullous pemphigoid antigens (BPAg1 and BPAg2), human beta4 integrin, and laminin 5 were measured. A statistically significant (P < 0.05) decline in the autoantibody titers to beta4-integrin was observed after 3.42 months of initiating the IVIg therapy. These titers were undetectable after 13 months of therapy. The titers of antibodies to BPAg1 and BPAg2 did not correlate with disease activity or response to therapy. Antibodies to laminins were not detected. In patients with MMP, autoantibody titers to beta4-integrin correlate with disease activity and response to therapy. 相似文献
148.
Sellon DC Knowles DP Greiner EC Long MT Hines MT Hochstatter T Tibary A Dame JB 《Clinical and diagnostic laboratory immunology》2004,11(6):1134-1139
Equine protozoal myeloencephalitis is a progressive neurologic disease of horses most commonly caused by infection with the apicomplexan parasite Sarcocystis neurona. Factors affecting neuroinvasion and neurovirulence have not been determined. We investigated the pathogenesis of infection with S. neurona in horses with severe combined immune deficiency (SCID). Two immunocompetent (IC) Arabian horses and two Arabian horses with SCID were infected orally with 5 x 10(5) sporocysts of S. neurona. Four IC horses and one SCID horse were infected intravenously (i.v.) with 5 x 10(8) merozoites of the WSU-1 isolate of S. neurona. Despite prolonged parasitemia and persistent infection of visceral tissues (skeletal muscle, cardiac muscle, lung, liver, and spleen) as demonstrated by PCR and culture, SCID horses did not develop neurologic signs after oral or i.v. infection. S. neurona was undetectable in the neuronal tissues of SCID horses by either PCR, immunohistochemistry, or culture. In contrast, although parasitemia was undetectable in orally infected IC horses and of only short duration in i.v. infected IC horses, four of six IC horses developed neurologic signs. S. neurona was detectable by PCR and/or culture of neural tissue but not visceral tissue of IC horses with neurologic disease. Infected SCID horses are unable to clear S. neurona from visceral tissues, but the infection does not result in neurologic signs; in contrast, IC horses rapidly control parasitemia and infection of visceral tissues but frequently experience neuroinvasion and exhibit clinical signs of neurologic disease. 相似文献
149.
150.
1. Whole-cell current responses to bath application of glycine, beta-alanine, and taurine were studied in medullary neurons cultured from embryonic rats. 2. Two current components were seen in the responses to bath application of agonist, one component that desensitized and another that did not. 3. The two current components have different dose-response characteristics, with the nondesensitizing component being activated more effectively at lower concentrations than the desensitizing component and also reaching its peak at lower concentrations. The agonist concentrations producing half-maximal responses are 26 +/- 4 (SE, n = 6) and 69 +/- 17 (n = 7) microM for the nondesensitizing and desensitizing components, respectively, for glycine; 54 +/- 7 (n = 9) and 127 +/- 37 (n = 7) microM for beta-alanine; and 153 +/- 24 (n = 9) 443 +/- 99 (n = 3) microM for taurine. Thus, for each component, the order of potency is glycine greater than beta-alanine greater than taurine. 4. When total responses to glycine, beta-alanine, and taurine are compared in the same cells, taurine and beta-alanine are less potent agonists than glycine, with relative potencies of 1:0.4:0.1 for glycine-beta-alanine-taurine. 5. The desensitizing component is more sensitive to strychnine than the nondesensitizing one. The strychnine concentrations that block 50% of the response to a control dose of agonist are 15 and 500 nM for the desensitizing and nondesensitizing components, respectively, for glycine; 60 nM and 1 microM for beta-alanine; and 18 and 500 nM for taurine. 6. The complete occlusion between the responses to glycine and beta-alanine or glycine and taurine suggests that these agonists activate the same receptors. 7. The two current components may be manifestations of one receptor population with complicated kinetics or two independent receptor populations. 相似文献