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81.
Riccardo Dolcetti Paola Zancai Roberta Cariati Mauro Boiocchi 《Leukemia & lymphoma》1998,29(3):269-281
Retinoids have been shown to be effective in the chemoprevention and treatment of certain human malignancies. In this review, we will summarize our recent results concerning the effects of retinoids on the proliferation and differentiation of Epstein-Barr virus (EBV)-immortalized lymphoblastoid B-cell lines (LCLs), an in vitro model of EBV-related lymphoproliferative disorders arising in immunosuppressed hosts. Retinoids proved to be powerful inhibitors of the proliferation of EBV-infected LCLs in vitro, with 13-cis-retinoic acid (RA), all-trans-RA, and 9-cis-RA being the most effective compounds. Of note, retinoid-induced growth arrest in vitro appears irreversible at drug concentrations (10--6 mol/L) which may be reached in man after oral systemic therapy. The antiproliferative activity exerted by retinoids on LCLs is a generalized phenomenon usually associated with a progressive accumulation in G0/G1 phases of treated cells. The strong upregulation of p27Kipl invariably observed in cells exposed to retinoids may contribute to the decreased number of cycling cells, probably by inhibiting the transition from the G1 to S phase. Moreover, we obtained evidence indicating that the antiproliferative effects of retinoids are not dependent on the induction of terminal differentiation of EBV-immortalized B lymphocytes. In fact, the modifications induced by retinoids relative to LCL morphology, phenotype (downregulation of CD19, HLA-DR, and s-Ig, and upregulation of CD38 and c-Ig), and IgM production were highly variable among the lines tested and often only slightly relevant. Finally, the antiproliferative activity exerted by retinoids on LCLs is not mediated by a direct modulation of viral latent antigens, since EBNA-2 and LMP-1 downregulation was a late event detected only in some cell lines. These results indicate that retinoids may be useful in the medical treatment of EBV-related lymphoproliferative disorders of immunosuppressed patients, particularly in the earlier phases of these diseases. 相似文献
82.
Polymorphisms of interleukin (IL)-1α, IL-1β, IL-6, IL-10, and IL-18 and the risk of ovarian cancer 总被引:10,自引:0,他引:10
Abigail W. Bushley Robert Ferrell Katharine McDuffie Keith Y. Terada Michael E. Carney Pamela J. Thompson Lynne R. Wilkens Ko-Hui Tung Roberta B. Ness Marc T. Goodman 《Gynecologic oncology》2004,95(3):269-679
OBJECTIVE: Recent studies of ovarian cancer have suggested a role for inflammation in carcinogenesis. Data from a population-based case-control study in Hawaii were examined to assess the relation between polymorphisms in cytokines involved with the inflammatory response, specifically members of the interleukin (IL) family and the incidence of ovarian cancer. PATIENTS AND METHODS: The analysis of 182 epithelial ovarian cancer cases and 219 controls focused on the polymorphisms in the following genes: IL-1alpha, IL-1beta, IL-6, IL-10, and IL-18. Genotype data were obtained from blood samples collected in participants' homes, and reproductive, demographic, and lifestyle histories were collected during interview. RESULTS: There were no significant odds ratios (ORs) for ovarian cancer by allelic variants in any of the IL genes after adjusting for age, ethnicity, education, oral contraceptive pill use, pregnancy, and history of tubal ligation. Although there was a significantly reduced risk of ovarian cancer risk among women with an IL-1alpha (-4845) T allele compared to women with two G alleles (OR: 0.59; 95% confidence interval: 0.37-0.97) after adjustment for age and ethnicity, the trend was not significant (p = 0.10). Further examination of the data suggested that women with at least one IL-18 variant allele (a G to C transition at position -137) were at significantly decreased risk of advanced ovarian cancer (OR: 0.51; 95% confidence interval: 0.28-0.90) compared to women with the IL-18 GG genotype. There was a significant difference in the risk of ovarian cancer associated with the IL-18 C allele by stage at diagnosis (p = 0.04 for homogeneity in the ORs): cases with IL-18 GC or CC genotypes were less likely to be diagnosed at regional/distant stages. Analysis of the data within ethnic subgroups revealed a significant positive association of the heterozygous IL-18 GC genotype with ovarian cancer risk among Native Hawaiian women (OR: 9.96; 95% CI: 1.88-52.90). The OR for ovarian cancer was not significant for Native Hawaiian women homozygous for the IL-18 C allele, but only one case and control had the IL-18 CC genotype. CONCLUSIONS: Overall, this study does not support an association of selected IL-1alpha, IL-1beta, IL-6, IL-10, or IL-18 polymorphisms with the risk for ovarian cancer. However, the IL-18 G137C variant may be a marker for ovarian cancer progression or metastasis. 相似文献
83.
Abnormal vascular tone in infants and children with lung hypoplasia: Findings from cardiac catheterization and the response to chronic therapy. 总被引:2,自引:0,他引:2
Roberta L Keller Phillip Moore David Teitel Samuel Hawgood John McQuitty Jeffrey R Fineman 《Pediatric critical care medicine》2006,7(6):589-594
OBJECTIVE: We describe four cases of chronic pulmonary hypertension in infants and children with chronic lung disease and pulmonary hypoplasia due to severe congenital diaphragmatic hernia (CDH) or congenital cystic adenomatoid malformation (CCAM). We report data from cardiac catheterization under various conditions: baseline respiratory support and room air, hyperoxic and inhaled nitric oxide challenge. We further report cardiac catheterization measures after chronic pulmonary vasodilator therapy with sildenafil alone or a combination of sildenafil and inhaled nitric oxide (three patients). DESIGN: Case series. SETTING: Tertiary academic center. PATIENTS: Infants and children ages 0-11 yrs with CDH (n = 3) or CCAM (n = 1) with evidence of chronic pulmonary hypertension by echocardiogram and cor pulmonale (n = 3). INTERVENTIONS: Catheterization and pulmonary vasodilator therapy. MEASUREMENTS AND MAIN RESULTS: Pulmonary vascular resistance, pulmonary arterial pressure, and changes in these measures were assessed. A 20% change in pulmonary vascular resistance was considered a clinically significant response. Ten catheterizations were performed in four patients. All patients had elevated pulmonary vascular resistance and pulmonary arterial pressures at initial catheterizations and significant vasodilation during inhaled nitric oxide. CONCLUSIONS: Chronic lung disease following pulmonary hypoplasia from CDH and CCAM is associated with abnormal pulmonary vascular tone in infants and children with evidence of chronic pulmonary hypertension. Chronic pulmonary vasodilator therapy may improve pulmonary vascular function and enhance lung growth in infants and children who are treated during their period of potential for rapid lung growth. 相似文献
84.
Evasio Pasini Anna Cargnioni Fiorella Pastore Roberta Razzetti Stefano Bongrani Gian Luca Gitti Roberto Ferrari 《Pharmacological research》2004,49(1):1-5
Neurohormonal activation has been shown to be a major factor in congestive heart failure progression and mortality. The beneficial effects obtained in clinical trials with angiotensin converting enzyme (ACE) inhibitors, beta-blockers and aldosterone antagonists have confirmed this hypothesis. 5,6-Diisobutirroyloxy-2-methyl-aminotetraline hydrochloride (nolomirole) is a selective agonist of prejunctional D(2)-dopaminergic and alpha(2)-adrenergic receptors. The stimulation of these receptors inhibits catecholamine release from sympathetic nerve endings. To confirm that this mechanism can be useful in congestive heart failure, we studied the effects of nolomirole on monocrotaline-induced congestive heart failure. The ACE inhibitor trandolapril was used as reference compound. Rats were given single intraperitoneal injection of either saline (control group; n=20) or monocrotaline (50 mg kg(-1)). Three days later, the monocrotaline-treated animals were randomly allocated (n=50 per group) to oral treatment with distilled water (vehicle group), nolomirole (0.25 mg kg(-1)) twice a day, or trandolapril (0.3 mg kg(-1)) once a day up to sacrifice. On the fourth week after monocrotaline injection, animals with signs of congestive heart failure were sacrificed for evaluation of heart hypertrophy and neuroendocrine alterations. Atrial natriuretic peptide (ANP) and alderosterone were determined by radioimmunoassay in plasma. Tissue norepinephrine concentration was quantified by high-pressure liquid chromatography. Nolomirole and trandolapril significantly reduced (a) hypertrophy of right atria and ventricles, (b) plasma levels of ANP and presence of pleural/peritoneal effusions and (c) norepinephrine depletion of right ventricle. These findings confirmed that nolomirole, like trandolapril, is able to attenuate the heart failure signs in the monocrotaline-induced congestive heart failure model. 相似文献
85.
86.
87.
When tissues are damaged, they usually heal. The cellular responses towards healing require the prior recognition that damage has occurred. High Mobility Group Box 1 protein (HMGB1) is a ubiquitous nuclear protein that is passively released by cells that have died in a traumatic, non-programmed way (necrosis). Several receptors for HMGB1 exist, and upon binding HMGB1 they alert leukocytes to extravasate from the blood into the affected tissue, trigger adaptive immunity and promote the migration and proliferation of cells (including stem cells) to repair the damaged tissue. Significantly, apoptotic cells modify their chromatin so as to bind HMGB1, which is not released. Several cell types (in particular inflammatory cells) when distressed have the ability to secrete HMGB1 actively, via a dedicated pathway, and thus produce a damage signal without dying. Because of its powerful activities, HMGB1 is involved in several disorders, including autoimmune ones. 相似文献
88.
Roberta Cocchiara Giovanna Di Trapani Antonina Azzolina Domenico Geraci 《Journal of immunoassay & immunochemistry》2013,34(4):337-352
Abstract An ELISA assay is described for the measurement of the smIgG. The method is based on the detection of cell-smIgG directly on the same microplate used for the culture. The cells, preincubated at 37°C for one hour, were cultured in the presence of S-ConA and serum-free medium for two days. Using this strategy, the background noise due to non specific adsorbtion of IgG to plastic wells and cytophilic antibodies was eliminated. The cells in the presence of S-ConA and serum-free medium adhered to the plastic wells, and the cell-smIgG were detected using an anti-human IgG covalently linked to alkaline phosphatase or its F(ab')2 fragment. The possibility of measuring the modulation of the expression of the cell-smIgG without any additional manipulation is stressed. 相似文献
89.
90.
This article reviews recent developments in health care law, focusing on controversy at the intersection of health care law and culture. The article addresses: emerging issues in federal regulatory oversight of the rapidly developing market in direct-to-consumer genetic testing, including questions about the role of government oversight and professional mediation of consumer choice; continuing controversies surrounding stem cell research and therapies and the implications of these controversies for healthcare institutions; a controversy in India arising at the intersection of abortion law and the rights of the disabled but implicating a broader set of cross-cultural issues; and the education of U.S. health care providers and lawyers in the theory and practice of cultural competency. 相似文献