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151.
P-glycoprotein targeting: a unique strategy to selectively eliminate immunoreactive T cells 总被引:4,自引:2,他引:4
T lymphocytes have been found to harbor P-glycoprotein (Pgp) and to demonstrate modulation of its ion channel transporter function according to the state of activation of T lymphocytes. We hypothesized that cytotoxic chemicals that are extruded by Pgp could be used to specifically eliminate immunoreactive T-cell populations. In this study, we evaluated the capacity of 4,5-dibromorhodamine methyl ester (TH9402), a photosensitizer structurally similar to rhodamine, a dye transported by Pgp, and which becomes highly cytotoxic on activation with visible light to selectively deplete alloreactive T lymphocytes. Stimulation of T cells with mitogens or allogeneic major histocompatibility complex-mismatched cells resulted in the preferential retention of the TH9402 rhodamine-derivative in activated T cells, both CD4+ and CD8+. Photodynamic cell therapy of TH9402-exposed T cells led to the selective elimination of immunoreactive T-cell populations. In addition, this treatment preserved resting T cells and their capacity to respond to third-party cells. Inhibition of Pgp enhanced cellular trapping of the dye in nonactivated T cells and resulted in their depletion after exposure to light. Targeting of Pgp-deficient cells may therefore represent an appealing strategy for the prevention and treatment of graft-versus-host disease and other alloimmune or autoimmune disorders. 相似文献
152.
Hegazi RA Mady HH Melhem MF Sepulveda AR Mohi M Kandil HM 《Inflammatory bowel diseases》2003,9(4):230-236
Nonsteroidal anti-inflammatory drugs decrease sporadic colorectal carcinoma and adenomas in patients with familial adenomatous polyposis and in rodent models of sporadic colon cancer and familial adenomatous polyposis. Similarly, selective cyclooxygenase 2 inhibitors decrease adenomas in humans and rodents. However, their effects on chronic colitis and colitis-associated neoplasia are unknown. Interleukin 10-/- mice (C57/B6) were fed regular chow (n = 20) or chow with celecoxib (1,500 ppm, n = 18) or rofecoxib (75 ppm, n = 20) for 12 weeks. Twenty-eight percent of the celecoxib group died versus 5% of the control and rofecoxib groups (p < 0.05 compared with control). Celecoxib and rofecoxib increased the incidence of colitis (26% vs. 92% and 68%, p < 0.01), colitis score (0.4 +/- 0.2 vs. 2.5 +/- 0.3 and 2 +/- 0.4, p < 0.01), aberrant crypt foci (0.5 +/- 0.3 vs. 3.7 +/- 2.6 and 2.8 +/- 0.7, p < 0.01), aberrant crypts per mouse (4.11 +/- 2.1 vs. 41.2 +/- 9.7 and 27.1 +/- 7.5, p < 0.01) and dysplasia (11% vs. 54% and 42%, p < 0.01). Similarly, indomethacin (9 ppm, n = 15) increased colitis score, aberrant crypt foci, and dysplasia after 27 days of treatment. Two selective cyclooxygenase 2 inhibitors exacerbate colitis and premalignant changes in the interleukin 10-/- mouse model of chronic colitis and colitis-associated colon carcinoma. 相似文献
153.
Ioannis?A?Bliziotis Konstantinos?Paraschakis Paschalis?I?Vergidis Antonia?I?Karavasiou Matthew?E?FalagasEmail author 《BMC infectious diseases》2005,5(1):16
Background
Trying to confront with the widespread burden of infectious diseases, the society worldwide invests considerably on research. We evaluated the contribution of different world regions in research production in Infectious Diseases. 相似文献154.
Antiatherogenic effect of Pistacia lentiscus via GSH restoration and downregulation of CD36 mRNA expression 总被引:3,自引:0,他引:3
Dedoussis GV Kaliora AC Psarras S Chiou A Mylona A Papadopoulos NG Andrikopoulos NK 《Atherosclerosis》2004,174(2):293-303
Pistacia lentiscus var. Chia (Anacardiaceae) grows almost exclusively on Chios Island, Greece, and gives a resinous exudate resin used for culinary purposes by Mediterranean people. We investigated the molecular mechanisms through which total polar extract of the resin inhibits oxidized low-density lipoprotein (oxLDL) cytotoxic effect on peripheral blood mononuclear cell (PBMC). Cells exposed to oxLDL underwent apoptosis and necrosis, dependent on the duration of exposure. When culturing cells with oxLDL and the polar extract concurrently, we observed inhibition of both the phenomena. Because under oxidative stress the pro-oxidant systems outbalance the antioxidant, potentially producing oxidative damage and ultimately leading to cell death, we measured the levels of intracellular antioxidant glutathione (GSH). Additionally, we measured CD36 expression, a class B scavenger receptor, on CD14-positive cells, as CD36 has been identified as the oxLDL receptor in macrophages and may play a pivotal role in atherosclerotic foam cell formation. oxLDL decreased GSH levels and upregulated CD36 expression. P. lentiscus extract restored GSH levels and downregulated CD36 expression, even at the mRNA level. In order to find out the biologically drastic constituents of the resin's polar extract, fractions derived from RP-HPLC analysis were examined for their antioxidant effect on oxidatively stressed PBMC. The triterpenoid fraction revealed remarkable increase in intracellular GSH. We suggest GSH restoration and downregulation of CD36 mRNA expression as the pathways via which P. lentiscus triterpenes exert antioxidant/antiatherogenic effect. Additionally, our results provide strong evidence of the resin's antiatherogenic effect; therefore it is credited with beneficial health aspects. 相似文献
155.
Allen NE Key TJ Dossus L Rinaldi S Cust A Lukanova A Peeters PH Onland-Moret NC Lahmann PH Berrino F Panico S Larrañaga N Pera G Tormo MJ Sánchez MJ Ramón Quirós J Ardanaz E Tjønneland A Olsen A Chang-Claude J Linseisen J Schulz M Boeing H Lundin E Palli D Overvad K Clavel-Chapelon F Boutron-Ruault MC Bingham S Khaw KT Bueno-de-Mesquita HB Trichopoulou A Trichopoulos D Naska A Tumino R Riboli E Kaaks R 《Endocrine-related cancer》2008,15(2):485-497
Epidemiological data show that reproductive and hormonal factors are involved in the etiology of endometrial cancer, but there is little data on the association with endogenous sex hormone levels. We analyzed the association between prediagnostic serum concentrations of sex steroids and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition using a nested case-control design of 247 incident endometrial cancer cases and 481 controls, matched on center, menopausal status, age, variables relating to blood collection, and, for premenopausal women, phase of menstrual cycle. Using conditional regression analysis, endometrial cancer risk among postmenopausal women was positively associated with increasing levels of total testosterone, free testosterone, estrone, total estradiol, and free estradiol. The odds ratios (ORs) for the highest versus lowest tertile were 2.66 (95% confidence interval (CI) 1.50-4.72; P=0.002 for a continuous linear trend) for estrone, 2.07 (95% CI 1.20-3.60; P=0.001) for estradiol, and 1.66 (95% CI 0.98-2.82; P=0.001) for free estradiol. For total and free testosterone, ORs for the highest versus lowest tertile were 1.44 (95% CI 0.88-2.36; P=0.05) and 2.05 (95% CI 1.23-3.42; P=0.005) respectively. Androstenedione and dehydroepiandrosterone sulfate were not associated with risk. Sex hormone-binding globulin was significantly inversely associated with risk (OR for the highest versus lowest tertile was 0.57, 95% CI 0.34-0.95; P=0.004). In premenopausal women, serum sex hormone concentrations were not clearly associated with endometrial cancer risk, but numbers were too small to draw firm conclusions. In conclusion, relatively high blood concentrations of estrogens and free testosterone are associated with an increased endometrial cancer risk in postmenopausal women. 相似文献
156.
Rocco IM Santos CL Bisordi I Petrella SM Pereira LE Souza RP Coimbra TL Bessa TA Oshiro FM Lima LB Cerroni MP Marti AT Barbosa VM Katz G Suzuki A 《Revista do Instituto de Medicina Tropical de S?o Paulo》2005,47(5):281-285
This paper reports the isolation of St. Louis encephalitis virus (SLEV) from a febrile human case suspected to be dengue, in S?o Pedro, S?o Paulo State. A MAC-ELISA done on the patient's acute and convalescent sera was inconclusive and hemagglutination inhibition test detected IgG antibody for flaviviruses. An indirect immunofluorescent assay done on the C6/36 cell culture inoculated with the acute serum was positive for flaviviruses but negative when tested with dengue monoclonal antibodies. RNA extracted from the infected cell culture supernatant was amplified by RT-PCR in the presence of NS5 universal flavivirus primers and directly sequenced. Results of BLAST search indicated that this sequence shares 93% nucleotide similarity with the sequence of SLEV (strain-MSI.7), confirmed by RT-PCR performed with SLEV specific primers. Since SLEV was identified as the cause of human disease, it is necessary to improve surveillance in order to achieve early detection of this agent in the state of S?o Paulo and in Brazil. This finding is also an alert to health professionals about the need for more complete clinical and epidemiological investigations of febrile illnesses as in the reported case. SLEV infections can be unrecognized or confused with other ones caused by an arbovirus, such as dengue. 相似文献
157.
Catherine Voisin Antonia SardellaAlfred Bernard 《International journal of hygiene and environmental health》2014,217(1):38-45
Rationale
Irritant chlorination products in swimming pools can cause respiratory problems in swimmers but their possible implication in allergies development is still unclear.Objectives
To assess prospectively whether early-life attendance at chlorinated pools increases the risks of IgE sensitization and of airways inflammation later during childhood.Methods
We conducted a two-year prospective study among 196 kindergarten children (mean age of 5.7 years, 54% of boys). We measured exhaled nitric oxide (eNO) and aeroallergen-specific IgE in nasal mucosa. Parents completed a questionnaire about the child's health, chlorinated pool attendance and potential confounders.Main Results
Ever swimming at indoor or outdoor chlorinated pools before the age of three years was associated with higher odds for new-onset IgE sensitization to house dust mite (adjusted odds ratio [aOR] 2.93, 95% confidence interval [CI] 1.14–7.55) and for new-onset increased eNO (>15 ppb; aOR, 4.54, 95% CI 1.48–13.9). For both outcomes, aORs increased dose-dependently with time spent in chlorinated pools with values reaching, respectively, 3.60 (95% CI 1.21–10.7) and 5.92 (95% CI 1.72–20.5) when the cumulative pool attendance exceeded 60 h These risks appeared independently of each other, of parental history of allergies and of pre-existing diseases, including eczema, which at baseline was more prevalent in early swimmers (aOR, 2.91; 95% CI 1.23–6.89). Such associations were not seen with IgE sensitization to pollen or cat allergens.Conclusion
Attendance at chlorinated swimming pools in early life is associated with higher risks of new-onset airways inflammation and IgE sensitization to house dust mite, independently of other risk factors. 相似文献158.
159.
160.
Carla Bastida Maria Antonia Also Juan Manuel Pericas Emili Letang Montse Tuset Josep Maria Miró 《Enfermedades infecciosas y microbiología clínica》2014