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61.
Karina R B Bastos Renato Barboza Rosa M Elias Luiz R Sardinha Marcos G Grisotto Cláudio R F Marinho Gustavo P Amarante-Mendes José M Alvarez Maria Regina D'Império Lima 《Journal of interferon & cytokine research》2002,22(12):1191-1199
Aiming to clarify the role of endogenous interleukin-12 (IL-12) in protective immunity against blood stages of Plasmodium chabaudi chabaudi (AS), we evaluated the course of infection in IL-12p40 gene knockout (IL-12p40KO) and wild-type (WT) C57BL/6 mice, focusing (1) on the ability of T cells to develop adequate type 1 responses and (2) on the potentiality of macrophages to respond to parasites, interferon-gamma (IFN-gamma), or both. We observed that IL-12p40KO mice develop significantly higher parasitemias during the acute infection, although mice from both groups clear the parasites within a month and similarly eliminate a secondary challenge. Thus, fully protective immunity to P. c. chabaudi can be generated in the absence of IL-12. However, this cytokine may promote parasite control during the early phase of infection. The increased acute parasitemia of IL-12p40KO mice was associated with both impaired IFN-gamma and nitric oxide (NO) response by spleen cells. Because stimulation with recombinant IFN-gamma (rIFN-gamma) failed to improve the NO response in IL-12p40KO macrophages, we investigated whether these cells have an intrinsic defect. Analysis of peritoneal macrophages revealed that IL-12p40KO cells produce higher levels of transforming growth factor-beta1 (TGF-beta1) compared with WT cells and respond to infected erythrocytes or rIFN-gamma by releasing little NO. Moreover, IL-12p40KO macrophages had a severely impaired ability to internalize opsonized infected erythrocytes, suggesting that the low effector profile assumed by these cells may compromise antibody-mediated immunity. Taken together, our results support the idea that the absence of IL-12p40 not only affects IFN-gamma production but also has deep consequences in macrophage effector functions that may contribute to exacerbation of the early phase of P. c. chabaudi malaria. 相似文献
62.
Zheng T Zhu Z Wang J Homer RJ Elias JA 《The Journal of allergy and clinical immunology》2001,108(4):489-496
The evolution of our understanding of IL-11 mirrors, in many ways, the problems that are faced by investigators in the post-genome era and the types of techniques that might need to be used to deal with these issues. IL-11 was discovered as a soluble factor in fibroblast supernatants that stimulated the proliferation of "IL-6-dependent" plasmacytoma cells. It was subsequently demonstrated to be an important stimulator of platelet reconstitution and a pleiotropic regulator of nonrespiratory tissues. In the lung, IL-11 is produced by a variety of structural cells and eosinophils in response to a variety of stimuli, including TGF-beta, major basic proteins, and viruses. IL-11 is also detected in exaggerated quantities at sites of virus infection. Its potential effector functions at these sites were defined with constitutive and inducible overexpression transgenic modeling systems which demonstrated that IL-11 causes nodular mononuclear infiltrates, airway remodeling with subepithelial fibrosis, airways obstruction, and airways hyperresponsiveness and can block alveolar development when expressed during development. In accord with these murine findings, IL-11 is selectively expressed in eosinophils and epithelial cells in patients with moderate and severe asthma where expression correlates directly with disease severity and inversely with FEV(1). Studies using transgenic mice also demonstrated that IL-11 inhibits antigen-induced tissue inflammation. Thus IL-11 might be an important regulator of inflammatory and remodeling responses in the asthmatic airway. 相似文献
63.
64.
Dose-intensive therapy for extensive-stage small cell lung cancer and extrapulmonary small cell carcinoma: long-term outcome. 总被引:1,自引:0,他引:1
Anthony D Elias Arthur T Skarin Paul Richardson Joseph Ibrahim Mary McCauley Emil Frei 《Biology of blood and marrow transplantation》2002,8(6):326-333
Treatment for extensive-stage small cell lung cancer (ES SCLC) or extrapulmonary small cell carcinoma (EPSC) is typically palliative. We set out to determine progression-free survival (PFS) and overall long-term survival of ES SCLC and EPSC patients, physiologically aged < or = 60 years, responding to first-line chemotherapy followed by high-dose combination alkylating agents with hematologic stem cell support. Patients in first-line chemotherapy response underwent stem cell collection (marrow, peripheral blood progenitor cells, or both) followed by high-dose therapy with 1 of 2 regimens: CBP (cyclophosphamide, cisplatin, and carmustine) or ICE (ifosfamide, carboplatin, and etoposide) with or without etanidazole. Involved-field radiotherapy was given to selected patients with oligometastatic disease distributed in sites allowing for reasonable radiation ports, and prophylactic cranial radiotherapy was given upon recovery to patients in complete response (CR) or near-CR. A total of 36 patients were treated. Of 29 patients with ES SCLC, 6 (21%) had achieved CR, 18 near-CR, and 5 partial response prior to high-dose therapy. Of 7 patients with EPSC, 3 (43%) had achieved CR, 3 had achieved near-CR, and 1 had progression of disease prior to high-dose therapy. Thirteen ES SCLC patients received high-dose CBP. Of the remaining 23 patients with SCLC or EPSC, 17 were treated with ICE and 6 with ICE plus etanidazole, a hypoxic cell sensitizer. Treatment-related mortality was 11% (4 of 36 patients). For all patients, the median event-free survival (EFS) was 5 months. The 2- and 5-year survivals after intensification were 12% (95% confidence interval [CI], 5%-31%) and 9% (95% CI, 3%-27%), respectively. Of the 30 patients in or near CR prior to high-dose therapy, 5 remain continuously progression-free (2 ES SCLC, 3 EPSC) for a median of 55 months (range, 1-96 months) after high-dose therapy. By multivariate analysis, factors associated with more favorable EFS were the use of a more aggressive induction regimen (ICE), and the EPSC histology. These factors were also associated with more favorable overall survival. Other factors associated with more favorable overall survival were the use of short induction therapy (< or = 4 cycles) and younger age (<50 years). Except for high-dose ICE with etanidazole, the use of high-dose systemic therapy in ES SCLC and EPSC was associated with low treatment-related morbidity and mortality over the past 5 years. Late complications were infrequent, and most patients returned to full-time work and activity, barring disease recurrence. Nonetheless, few patients with ES SCLC have progression-free long-term survival. We conclude that high-dose therapy is not indicated as an approach for ES SCLC, except as part of an investigative trial. Conversely, 3 of the 7 patients with EPSC remain relapse-free (range, 1-96 months), warranting further phase II evaluation of this approach in this population. 相似文献
65.
K A Elias A K Das D Pardue C B Coulam J K Critser E S Critser 《American journal of reproductive immunology (New York, N.Y. : 1989)》1989,21(3-4):82-86
Published reports of pregnancy associated thrombocytopenia in mice have utilized the Quackenbush strain. The inability of some laboratories to verify this observation in other mouse strains prompted us to report our findings by using Swiss Albino ICR mice. In Exp. 1, pregnant and pseudopregnant mice were bled prior to mating (time 0) and daily on day 1 (vaginal plug) through day 7. In Exp. 2, media from 24 hr cultures of 2-cell mouse embryos or media from unfertilized oocytes were injected into splenectomized mice. Animals were bled at time 0 (before injection) and at 30, 60, and 120 min after injection. In Exp. 3, splenectomized mice were treated with either media from 2-cell stage embryos or with media supplemented with synthetic platelet-activating factor (PAF: 0.05, 0.1 or 0.2 micrograms). Animals were bled as in Exp. 2. Platelet numbers were determined in duplicate from each blood sample by using a hemacytometer. In Exp. 4, antagonist (SRI 63-441) or vehicle was administered to mated mice on days 1 through 4 of pregnancy. Animals were examined on day 8 to determine number of developing conceptuses. In Exp. 1-3, data were analyzed by using ANOVA for repeated measures, and in Exp. 4 data were analyzed by chi-square analysis. In Exp. 1, there was a treatment x time interaction (P less than .06) due to transient thrombocytopenia in pregnant but not pseudopregnant mice.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
66.
Yu H Lee MH Starck L Elias ER Irons M Salen G Patel SB Tint GS 《Human molecular genetics》2000,9(9):1385-1391
The Smith-Lemli-Opitz syndrome (SLOS; also known as the RSH syndrome) is an autosomal recessive genetic disorder, leading to characteristic multi-organ developmental abnormalities, dysmorphic facies, limb malformations and mental retardation. Mutations in the gene for Delta(7)-dehydrocholesterol reductase (Delta(7)-reductase), which catalyzes the last step in cholesterol biosynthesis, cause the disease. We screened 32 patients with SLOS, 28 from the USA and four from Sweden. Twenty-two different nucleotide changes, predicted to be disease-causing mutations, were identified; 20 missense mutations, one nonsense mutation and one splice-site mutation involving the exon 9 acceptor site (IVS8 -1G-->C) were detected. All probands were heterozygous for mutations. Twelve of these mutations have not been reported previously, including missense mutations L148R, F168I, D175H, P179L, P243R, F284L, N287K, F302L, R404S, Y462H, R469P and one nonsense mutation W37X [corrected]. Coupled with previously reported mutations, these findings bring the total of different Delta(7)-reductase mutations to 36. These are distributed throughout the coding sequence of the Delta(7)-reductase gene except exons 3 and 5, with a clustering in exon 9. Three mutations account for 54% of those observed in our cohort, the splice acceptor site mutation IVS8 -1G-->C (22/64 alleles, 34%), T93M (8/64, 12.5%) and V326L (5/64, 7.8%). Severity of SLOS was negatively correlated with both plasma cholesterol and relative plasma cholesterol, but not with 7-dehydrocholesterol, the immediate precursor, confirming previous observations. However, no correlation was observed between mutations and phenotype, suggesting that the degree of severity may be affected by other factors. We estimate that between 33 and 42% of the variation in the SLOS severity score is accounted for by variation in plasma cholesterol. Thus, factors other than plasma cholesterol are additionally involved in determining severity. 相似文献
67.
68.
Condensation of benzamidine hydrochloride with acetanhydride gives 2-methyl-4.6-diphenyl-s-triazine with yields of more than 90%. The corresponding reaction of terephthaldiamidine dihydrochloride leads to poly[(6-methyl-2.4-s-triazinediyl)-1.4-phenylene] of low degree of polymerization, soluble in conc. sulfuric acid. Benzamidine-N-carboxylic acid ethylester is converted to 2-hydroxy-4.6-diphenyl-s-triazine in a yield of 99% by heating. Terephthaldiamidine-di-N-carboxylic acid ethylester decomposes by heat treatment under loss of ethyl carbamate to the insoluble white poly[(6-hydroxy-2.4-s-triazinediyl)-1.4-phenylene]. 相似文献
69.
Ynte M Ruigrok Rim Elias Cisca Wijmenga Gabri?l J E Rinkel 《Cardiovascular pathology》2008,17(1):40-47
BACKGROUND: Genetic factors are likely to be involved in the pathogenesis of intracranial, ascending thoracic aorta, and infrarenal aortic abdominal aneurysms. Common genetic risk factors for these three types of aneurysms have been suggested. This review describes the results of whole-genome linkage studies on intracranial, thoracic aorta, and aortic abdominal aneurysms, and compares the genomic loci identified in these studies in search of possible common genetic risk factors for the three aneurysmal types. METHODS: A literature search of all whole-genome linkage studies performed on intracranial, thoracic aorta, and aortic abdominal aneurysms was performed. The genomic loci identified in these studies were described and compared in search of similarities between them. RESULTS: Five chromosomal regions on 3p24-25, 4q32-34, 5q, 11q24, and 19q that may play a role in the pathogenesis of two or more aneurysmal types were identified: 3p24-25 for thoracic aorta and intracranial aneurysms; 4q32-34 for aortic abdominal and intracranial aneurysms; 5q for thoracic aorta and intracranial aneurysms; 11q24 for thoracic aorta, aortic abdominal, and intracranial aneurysms; and 19q for aortic abdominal and intracranial aneurysms. CONCLUSIONS: Five chromosomal regions that may include common genetic factors for intracranial, thoracic aorta, and aortic abdominal aneurysms were identified. Further studies are needed to explore these chromosomal regions in different aneurysm patient groups and may further help to unravel the disease pathogenesis of aneurysms in general. 相似文献
70.
Kessel A Rosner I Rozenbaum M Zisman D Sagiv A Shmuel Z Sabo E Toubi E 《Journal of clinical immunology》2004,24(1):30-36
Our objectives were (1) to compare lymphocyte subpopulation apoptosis rates in SSc patients versus healthy controls and (2) to compare Bcl-2 and NF-kappa B expression in cultured CD8 lymphocytes of SSc patients versus controls. Peripheral blood samples were obtained from 27 SSc patients meeting the American College of Rheumatology criteria for SSc and 28 healthy individuals. Mononuclear cells were isolated by Ficoll-Hypaque density gradient separation and cultured for 48 hr. For determination of apoptosis within specific cell populations, samples were labeled with PE-conjugated monoclonal antibody to CD8, CD4, and a FITC-conjugated monoclonal antibody to Annexin V. Flow cytometry was carried out with a FACS operating with Cellquest software. CD8+ lymphocytes were positively selected with magnetic microbeads conjugated to antihuman CD8. CD8 T cells were separated, then incubated with activation for 48 hr, and NF-kappa B and Bcl-2 analysis was carried out using Western immunoblotting. The CD4:CD8 ratio was increased in SSc compared to controls (2.6 +/- 1.13 vs.1.87 +/- 0.76; P = 0.018). The spontaneous apoptosis rate of SSc CD8 lymphocytes was increased compared to that of controls of (21.9 +/- 13.7 vs. 13.3 +/- 9.9; P = 0.019). No difference was found in the rate of CD4 apoptosis of SSc patients versus controls (9.8 +/- 5.2 vs. 7.18 +/- 4.89%; P = ns). The expression of NF-kappa B in SSc CD8 lymphocytes was decreased compared with that of CD8 lymphocytes from healthy controls (144 +/- 13 vs. 188 +/- 11; P = 0.018). Whereas expression of Bcl-2 was similar in activated CD8+ T cells of SSc patients and healthy controls, CD8+ T cell apoptosis rate was found to be in reverse correlation with expression of NF-kappa B in these cells ( r = - 0.53, P = 0.029). The increased CD4:CD8 ratio in SSC may result from increased CD8+ T cell apoptosis. Increased SSc CD8 T cell apoptosis is associated with low levels of NF-kappa B. 相似文献