Citations of BMS225/2
Preoperative prediction of pediatric patients with effusions and edema following cardiopulmonary bypass surgery by serological and routine laboratory data
Bocsi,József; Hambsch,Jörg; Osmancik,Pavel; Schneider,Peter; Valet,Günter; Tárnok,Attila
Critical Care 2002;6:226-233.
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Abstract
Aim Postoperative effusions and edema and capillary leak syndrome in children after cardiac surgery with cardiopulmonary bypass constitute considerable clinical problems. Overshooting immune response is held to be the cause. In a prospective study we investigated whether preoperative immune status differences exist in patients at risk for postsurgical effusions and edema, and to what extent these differences permit prediction of the postoperative outcome. Method One-day preoperative serum levels of immunoglobulins, complement, cytokines and chemokines, soluble adhesion molecules and receptors as well as clinical chemistry parameters such as differential counts, creatinine, blood coagulation status (altogether 56 parameters) were analyzed in peripheral blood samples of 75 children (aged 318 years) undergoing cardiopulmonary bypass surgery (29 with postoperative effusions and edema within the first postoperative week). Results Preoperative elevation of the serum level of C3 and C5 complement components, tumor necrosis factor-¦, percentage of leukocytes that are neutrophils, body weight and decreased percentage of lymphocytes (all P < 0.03) occurred in children developing postoperative effusions and edema. While single parameters did not predict individual outcome, >86% of the patients with postoperative effusions and oedema were correctly predicted using two different classification algorithms. Data mining by both methods selected nine partially overlapping parameters. The prediction quality was independent of the congenital heart defect. Conclusion Indicators of inflammation were selected as risk indicators by explorative data analysis. This suggests that preoperative differences in the immune system and capillary permeability status exist in patients at risk for postoperative effusions. These differences are suitable for preoperative risk assessment and may be used for the benefit of the patient and to improve cost effectiveness.
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Cytokines and lipid peroxidation in alcoholics with chronic hepatitis C virus infection
Castellano-Higuera,Ana; Gonzalez-Reimers,Emilio; Aleman-Valls,M.Remedios; Abreu-Gonzalez,Pedro; Santolaria-Fernandez,Francisco; Vega-Prieto,Maria Jose De La; Gomez-Sirvent,Juan Luis; Pelazas-Gonzalez,Ricardo
Alcohol and Alcoholism 2008;43:137-142.
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Abstract
A major cause of liver cirrhosis and hepatocarcinoma is chronic infection by hepatitis C virus. Ethanol consumption is the most significant environmental factor that exacerbates the progression of chronic hepatitis C to liver cirrhosis and hepatocarcinoma, perhaps due to increased cytokine secretion together with increased lipid peroxidation. In this study, we compare the intensity of lipid peroxidation (estimated as malondialdehyde (MDA) serum levels), the antioxidant status, (measured as glutathione peroxidase (GPX) and superoxide dismutase (SOD) activities in red blood cells), and levels of cytokines derived from Th1 cells (such as interferon gamma (IFNG)), Th2 cells (such as interleukin (IL)-4), Th3 cells (such as transforming growth factor beta (TGF-{beta})), and IL-6, IL-8, and tumor necrosis factor (TNF)-{alpha} in patients affected by chronic hepatitis C virus infection, 26 drinkers of alcohol and 40 nondrinkers of alcohol. Patients showed significantly higher TNF-{alpha} (Z = 4.92, P < 0.001), IL-8 (Z = 4.95, P < 0.001), IFNG (Z = 2.81, P = 0.005), TGF-{beta} (t = 2.12, P = 0.037), MDA (Z = 5, P < 0.001), but lower IL-6 (Z = 3.61, P < 0.001) and GPX (F = 4.30, P < 0.05) than controls, whereas no differences were observed regarding IL-4 (Z = 0.35, P = 0.72), GPX and SOD activities. Alcoholics showed significantly higher TNF-{alpha}, but lower IL-4, MDA, and GPX, than nonalcoholics. TNF-{alpha} was significantly related to albumin and prothrombin activity, whereas TGF-{beta} was significantly related to MDA levels. Thus, cytokine secretion is altered in HCV infection. This alteration mainly consists of a stimulation of Th1 cytokines and an inhibition--or at least, no stimulation--of Th2 cytokines; these changes are especially marked among alcoholics with HCV infection, and are accompanied by raised TGF-{beta}
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T-cell reactivity to glutamic acid decarboxylase in stiff-man syndrome and cerebellar ataxia associated with polyendocrine autoimmunity
COSTA,M.; SAIZ,A.; CASAMITJANA,R.; CASTANER,M.FERNANDEZ; SANMARTI,A.; GRAUS,F.; JARAQUEMADA,D.
Clinical and Experimental Immunology 2002;129:471-478.
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Abstract
SUMMARY Antibodies to glutamic acid decarboxilase (GAD-Abs) are present in the serum of 60-80% of newly diagnosed type 1 diabetes (DM1) patients and patients with autoimmune polyendocrine syndrome (APS) associated with DM1. Higher titre of GAD-Abs are also present in the serum of 60% of patients with stiff-man syndrome (SMS) and all reported patients with cerebellar ataxia associated with polyendocrine autoimmunity (CAPA). Several studies suggest that GAD-Abs may play a critical role in the pathogenesis of SMS and CAPA but little is known about T-cell responsiveness to GAD-65 in these neurological diseases. To analyse cell-mediated responses to GAD, we studied the peripheral blood lymphocyte proliferation and cytokine responses to recombinant human GAD-65 in 5 patients with SMS, 6 with CAPA, 9 with DM1, 8 with APS and 15 control subjects. GAD-65-specific cellular proliferation was significantly higher in SMS than in CAPA, DM1, APS or controls. In contrast, only T cells from CAPA patients showed a significantly high production of interferon-gamma after GAD stimulation, compared to all other patients and controls. No differences were found for IL-4 production. These results suggest that, despite similar humoral autoreactivity, cellular responses to GAD are different between SMS and CAPA, with a greater inflammatory response in CAPA, and this difference may be relevant to the pathogenesis of these diseases
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TGF-[beta]1 and IL-4 downregulate human papillomavirus-16 oncogene expression but have differential effects on the malignant phenotype of cervical carcinoma cells
Donalisio,Manuela; Cornaglia,Maura; Landolfo,Santo; Lembo,David
Virus Research 2008;132:253-256.
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Abstract
Host immune response to human papillomavirus (HPV) is a crucial factor in viral clearance and control of persistent infections. The existence of an intercellular control mechanism mediated by cytokines to suppress HPV-gene transcription and to prevent malignant conversion of HPV-infected cells, has been postulated. In a previous study, we demonstrated the inhibitory activity of several cytokines on the HPV-16 long control region (LCR)-driven transcription; among these, IL-4 was reported as a LCR inhibitor for the first time and proposed as a candidate for further studies. Here, we addressed the question of whether IL-4 represses HPV-16 oncogene transcription and exerts antitumor activity in HPV-16 positive cervical carcinoma cell lines. Results indicated that downregulation of E6 and E7 levels by IL-4 in CaSki cells is weaker than that exerted by TGF-[beta]1, a known LCR inhibitor, although both cytokines are equally active in suppressing LCR-driven transcriptional activity in a reporter cell line. Moreover, only TGF-beta rescued p53 expression, Rb response pathway, and induced cellular senescence. SiHa cells were unresponsive to both cytokines. These findings suggest that the two cytokines may play a role in the control of HPV infections, however, cervical carcinoma cells developed a partial or a total resistance to their inhibitory activity.
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Oxidative Status and Its Contribution to Extracellular Cytokine Secretion in Children with Acute Lymphoblastic Leukemia
Drabko,Katarzyna; Bojarska-Junak,Agnieszka; Kowalczyk,Jerzy R.
Blood (ASH Annual Meeting Abstracts) 2006;108:4471› Link
Abstract
Recent data suggest that oxidative-antioxidative imbalance may influence cytokine secretion in children with acute lymphoblastic leukemia (ALL). Plasma cytokines concentrations are reported to have an effect on clinical course of the patients with lymphoid malignancies. The aim of the study was analysis of oxidative status (Malonylodialdehyde, MDA) and antioxidant defense (Superoxide dismutase, SOD; glutathione peroxidase, GPX; total antioxidant status, TAS and vitamin E) in peripheral blood and evaluation of plasma concentration of IL-2, IL-4, IL-10 and TNF-alpha in children with acute lymphoblastic leukemia. Material and methods: Study group consisted of 23 newly diagnosed ALL children, including 13 boys and 10 girls, with median age 5 years (range, 0.5-16). Control group consisted of 21 healthy children (11 boys and 7 girls) with median age 7 years (range, 2-17). TAS, SOD, GPX status were estimated using commercially available Randox Laboratories Ltd kits. Vitamin E and MDA plasma concentrations were measured spectrofluorimetrically. Cytokine concentrations were measured by quantitative immunoassay tests: IL-2 and IL-4 plasma levels were assessed using Bender MedSystems test (Vienna, Austria), IL-10 and TNF-alpha by R&D system tests. All assays were performed twice: on diagnosis and 6 weeks thereafter. Results: GPX activity in study group was significantly higher before and during treatment than in control subjects (1.5-fold, p=0.02 and 2-fold, p=0.0007, respectively). MDA concentrations were higher in ALL group before treatment (1.4-fold, p=0.0001) and 6 weeks thereafter (1.2 fold, p=0.01) than in control group. SOD activity, TAS and vitamin E concentrations did not differ between the groups. IL-10 level was found to be significantly increased on ALL diagnosis, but not during therapy, when compared to control group (2-fold, p=0.02). TNF-alpha level was higher in patients before treatment then during treatment (3-fold, p=0.02) and as compare to the controls (2,5-fold, ns). IL-2 and IL-4 plasma concentrations were comparable in all groups in both time points. There was a correlation in children with ALL after 6 weeks therapy between MDA and IL-10 concentrations (r=0.59, p<0,05) as well as MDA and TNF-alpha concentrations (r=0,58, p<0,05). In control group MDA was correlated with IL-10(r=0.59, p<0.05). Median follow-up of the study group is 23 months, and at that time relapses occurred in 3 out of 23 patients. 2-fold decrease in median GPX were observed in patients, who relapsed afterward,. Median IL-10 plasma concentrations in children, who subsequently relapsed were 4-fold higher at diagnosis and 8-fold higher after 6 weeks of therapy then in patients who are still in remission (despite of achieving complete remission by all study group at 6th week of treatment). Conclusions: Oxidation process in plasma of children with ALL is significantly increased on diagnosis. Pro-oxidative status may contribute to IL-10 and TNF secretion and affect efficacy of treatment
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Aqueous and Serum Interferon {gamma}, Interleukin (IL) 2, IL-4, and IL-10 in Patients With Uveitis
Lacomba,Manuel Santos; Martin,Carmen Marcos; Chamond,Rafael Ramirez; Galera,Jose Maria Gallardo; Omar,Mohamed; Estevez,Eduardo Collantes
Archives of Ophthalmology 2000;118:768-772.
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Abstract
Objective To determine the cytokine profile in aqueous humor and peripheral blood from patients with uveitis. Methods Cytokines (interferon [IFN]-{gamma}, interleukin [IL] 2, IL-4, and IL-10) were measured in aqueous humor and peripheral blood samples from 23 patients with uveitis and 16 patients undergoing operation for uncomplicated cataracts (control group) by means of an enzyme-linked immunosorbent assay. Results Aqueous and serum samples from patients with uveitis showed higher levels of IFN-{gamma} and IL-2 than those of controls (P<.001). Similarly, serum IL-10 levels were slightly higher in the uveitis group (P=.002). No differences were found between uveitis and control groups for aqueous and serum IL-4 or aqueous IL-10 levels. In patients with uveitis, IFN-{gamma} levels were significantly higher in serum than aqueous (P<.001), whereas IL-2 levels were higher in aqueous than in serum (P<.001). Serum IFN-{gamma} levels correlated with severe visual damage (r=0.44; P=.03). Conclusions Aqueous and serum levels of IFN-{gamma} and IL-2 were elevated in patients with uveitis, suggesting a predominantly type 1 response (high IFN-{gamma} and low IL-4 levels). Elevated serum IFN-{gamma} level seems to predispose the patient to more serious loss of vision
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LIPID PEROXIDATION AND SERUM CYTOKINES IN ACUTE ALCOHOLIC HEPATITIS
SANCHEZ PEREZ,M.J.; GONZALEZ-REIMERS,E.M.I.L.; SANTOLARIA-FERNANDEZ,F.R.A.N.; DE LA VEGA-PRIETO,MARIA JOSE; MARTINEZ-RIERA,A.N.T.O.; GONZALEZ,PEDRO ABREU; RODRIGUEZ RODRIGUEZ,E.V.A.; DURAN-CASTELLON,M.CARMEN
Alcohol and Alcoholism 2006;41:593-597.
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Abstract
Aims: Increased exposure of Kupffer cells to intestinal-borne Gram-negative bacteria enhances the metabolism and leads to cytokine production by these cells. Activation of Kupffer cells increases free radical release, which may, in turn, enhance cytokine secretion, creating a positive feedback loop, which contributes to liver inflammation. Cytokines act on T cells, inducing their proliferation and secretion of additional interleukins. Lipid peroxidation products (malondialdehyde; MDA) form adducts with proteins and acetaldehyde, triggering a T cell immune response. Controversy exists about the predominance of either Th-1 or Th-2 cellular responses. We performed the present study in order to analyse the cytokine pattern in patients with acute alcoholic hepatitis, its relation to MDA and the relation between all these parameters and liver function and prognosis. Subjects and methods: The study included 53 male alcoholics, 47 followed up for a median time of 32 months, during which 17 of them died. We measured serum MDA, tumour necrosis factor-alpha, interferon gamma (IFNG) and interleukins (IL) 4, 6, 8, and 10. Results: MDA levels were raised in cirrhotics and non-cirrhotics with alcoholic hepatitis, maintaining a relationship with bilirubin and Maddrey index, and with mortality in the univariate analysis. Both IFNG and IL-4 were raised in our patients compared with controls, as well as IL-8, and IL-6, but IL-10 were below the detection limit in the majority of cases, especially in cirrhotics. Using a Cox regression model, Maddrey index displaced MDA in the survival analysis. Conclusions: Our data lend support to the hypothesis that activation of both Th-1 and Th-2 cell subsets take place. MDA levels are raised in alcoholics with alcoholic hepatitis and are closely related to liver function derangement and to survival, although this is displaced by Maddrey index using Cox regression model
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Tuberculosis associated with Mycobacterium tuberculosis Beijing and non-Beijing genotypes: a clinical and immunological comparison
Sun,Yong Jiang; Lim,T.K.; Ong,Adrian Kheng Yeow; Ho,Benjamin Choon Heng; Seah,Geok Teng; Paton,Nicholas I.
BMC Infectious Diseases 2006;6:105› Link
Abstract
The Mycobacterium tuberculosis Beijing genotype is biologically different from other genotypes. We aimed to clinically and immunologically compare human tuberculosis caused by Beijing and non-Beijing strains. Methods Pulmonary tuberculosis patients were prospectively enrolled and grouped by their M. tuberculosis genotypes. The clinical features, plasma cytokine levels, and cytokine gene expression levels in peripheral blood mononuclear cells (PBMC) were compared between the patients in Beijing and non-Beijing groups. Results Patients in the Beijing group were characterized by significantly lower frequency of fever (odds ratio, 0.12, p = 0.008) and pulmonary cavitation (odds ratio, 0.2, p = 0.049). Night sweats were also significantly less frequent by univariate analysis, and the duration of cough prior to diagnosis was longer in Beijing compared to non-Beijing groups (medians, 60 versus 30 days, p = 0.048). The plasma and gene expression levels of interferon (IFN) ¦ and interleukin (IL)-18 were similar in the two groups. However, patients in the non-Beijing group had significantly increased IL-4 gene expression ( p = 0.018) and lower IFN-¦ : IL-4 cDNA copy number ratios ( p = 0.01). Conclusion Patients with tuberculosis caused by Beijing strains appear to be less symptomatic than those who have disease caused by other strains. Th1 immune responses are similar in patients infected with Beijing and non-Beijing strains, but non-Beijing strains activate more Th2 immune responses compared with Beijing strains, as evidenced by increased IL-4 expression
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