Circulating levels of soluble Fas ligand and soluble Fas in patients with chronic obstructive pulmonary disease

Fas- and tumour necrosis factor (TNF) receptor-mediated apoptosis are known to be two principal apoptotic mechanisms in humans. Although there are several distinctions between these two systems, in vitro studies have demonstrated similar hypoxic activation and a functional relationship. Since patients with chronic obstructive pulmonary disease (COPD) show chronic hypoxaemia and the activation of the TNF-alpha system, we investigated whether these pathophysiological changes influence the Fas-Fas ligand system. We measured the circulating soluble Fas ligand (sFas-L) level, an inducer of apoptosis, and the soluble Fas receptor (sFas) level, an inhibitor of apoptosis, in 34 COPD patients and 35 age-matched healthy controls. In addition, we investigated the relationships between the levels of sFas-L or sFas and clinical variables including the TNF-alpha system; circulating TNF-alpha and soluble TNF-receptor (sTNF-Rs: sTNF-R55 and R75) levels, in the COPD patients. Although circulating TNF-alpha, sTNF-R55 and R75 levels were significantly higher in the COPD patients than in the healthy controls, serum level of sFas-L (Fisher's exact probability test; P = 0.26) and plasma level of sFas [COPD patients vs. controls; mean (SD); 3.74 (0.63) vs. 3.67 (0.48) ng/ml; P = 0.89) were not increased in the COPD patients. There was no significant correlation between the levels of sFas-L or sFas and clinical variables in COPD patients. These results suggest that the Fas-Fas ligand system does not independently play an important role in the pathophysiology of patients with COPD.     

Increased circulating levels of soluble Fas ligand are correlated with disease activity in patients with fibrosing lung diseases

OBJECTIVE: The Fas-Fas ligand (FasL) pathway is one of the important apoptosis-signalling molecule systems. We previously determined that this pathway may be involved in the pathogenesis of fibrosing lung diseases. In the present study, we evaluated the clinical significance of the levels of soluble forms of Fas (sFas) and FasL (sFasL) in serum from patients with fibrosing lung diseases. METHODOLOGY: We measured sFas, sFasL, KL-6 (a measure of alveolar type II cell damage), surfactant protein D (SP-D), and surfactant protein A (SP-A) levels in serum from 35 patients with idiopathic pulmonary fibrosis (IPF), 17 patients with interstitial pneumonia associated with collagen vascular diseases (CVD-IP), and 13 normal healthy controls using enzyme-linked immunosorbent assays (ELISA). RESULTS: The serum levels of sFasL were significantly increased in patients with active IPF and CVD-IP, compared with those with inactive disease and controls. There was no significant difference in sFasL levels between patients with inactive disease and controls. Serum sFasL levels were significantly correlated with lactate dehydrogenase and KL-6 levels in IPF. The decrease in sFasL levels following corticosteroid therapy was not correlated with the clinical course of IPF. There was no significant difference in serum sFas levels between IPF or CVD-IP patients and controls. CONCLUSIONS: Although further studies need to be performed on a large number of patients with histologically proven IPF or CVD-IP, it would seem that serum sFasL levels may reflect the activity of IPF and CVD-IP.     

Circulating soluble Fas ligand correlates with disease activity in Graves' hyperthyroidism

Apoptosis of thyrocytes may play an important role in the pathogenesis of autoimmune thyroiditis. Meanwhile, the Fas/Fas ligand (FasL) apoptosis pathway has received much attention in physiological homeostasis and immune regulation in various thyroid diseases, including Graves' hyperthyroidism (GD). FasL is a type II membrane protein of the tumor necrosis factor family, and induces apoptosis when it binds to Fas. Soluble FasL (sFasL) may also exert cytotoxic activity against Fas-expressing cells by producing trimerization of Fas molecule, but soluble Fas (sFas) is an apoptotic inhibitor. To determine the role of circulating sFas/sFasL in modulating disease activity of GD, we examined the circulating levels of sFas/sFasL in GD patients with various levels of anti-thyrotropin-stimulating hormone (TSH) receptor antibodies (TRAb). Serum samples were obtained from 22 consecutive untreated hyperthyroid GD patients with higher TRAb level (63.8% +/- 12.5%, group I) and 22 treated euthyroid GD patients, who were in a state of disease remission, with lower TRAb level (7.9% +/-5.9%, group II). The levels of sFas were significantly higher in group I (1.56 +/- 0.26 ng/mL) than in group II (0.76 +/- 0.26 ng/mL, P <.01). The levels of sFasL were also significantly higher in group I patients (0.153 +/- 0.018 ng/mL) than in group II patients (0.126 +/- 0.012 ng/mL, P <.01). A significant correlation was found between sFasL levels and TRAb activity in all GD patients (r = 0.69, P <.01). Because changes in sFasL levels and TRAb levels occur in parallel, increased serum sFasL in patients with GD may contribute to homeostasis in the thyroid. Serum sFasL may be considered to be a candidate marker for evaluating disease aggression or regression in GD.     

The evaluation of soluble Fas and soluble Fas ligand levels of bronchoalveolar lavage fluid in lung cancer patients

Fas-Fas Ligand (FasL) is one of the major mediator system that activates programmed cell death. Cleavage of membranebound FasL by a metalloproteinase-like enzyme resulted in the formation of soluble FasL (sFasL). sFasL as well as the transmembrane form of FasL binds to Fas and transduces apoptotic signal in Fas-expressing cells. It's suggested that soluble Fas (sFas) and sFasL has an impact on tumor progress and immune escape feature of tumor cells from the host immune system. Since Fas antigen expression in the lungs has been localized to alveolar and bronchial epithelial cells, in this study we aimed to investigate the sFas (pg/mL) and sFasL levels (pg/mL) of bronchoalveolar lavage (BAL) fluid in lung cancer patients. Study population was consisted of 27 patients with lung cancer (mean age 62.9 +/- 10.7 years, 25 control subjects (mean age 47.9 +/- 13.9 years). BAL was performed under local anesthesia, on the unaffected lung of patients; either subsegments of right middle or lingula. BAL sFas and sFasL were evaluated by using ELISA method. The mean levels of sFas was 60.8 +/- 56.8 in lung cancer patient and 39.5 +/- 25.9 in control subjects (p> 0.05). The mean levels of sFasL was 51.6 +/- 39.2 in cancer patient and 41.2 +/- 27.4 in control subjects (p> 0.05). In conclusion, although we did not observe any significant difference between two groups, higher BAL levels of sFas and sFasL levels in lung cancer patients than control subjects, made us thought that apoptosis might have a role development and progression of lung cancer.     

Circulating soluble Fas levels in patients with hepatitis C virus infection and interferon therapy

Background The clinical relevance of the circulating soluble form of the Fas-Receptor (sFas) was investigated in patients with hepatitis C receiving type 1 interferon (IFN) therapy.Methods sFas was quantified by enzyme-linked immunosorbent assay in 66 hepatitis C virus (HCV) carriers and 30 HCV-naive or previously infected controls. The levels were then monitored during enhanced treatment with type 1 IFNs in 15 chronic hepatitis C patients.Results The HCV carriers had high levels of sFas compared with controls (3.8 ± 1.3 vs 2.7 ± 0.8ng/ml; P < 0.001). sFas levels in patients with chronic HCV infection were directly related to serum alanine aminotransferase levels (r = 0.440; P < 0.001) and the histological grade (r = 0.403; P = 0.019). Among necroinflammatory reactions, only piecemeal necrosis showed a correlation with sFas levels (r = 0.556; P = 0.001). Pretreatment sFas levels, however, were not predictive of therapeutic outcomes. A sustained virological response to enhanced IFN therapy showed a relation to only the pretreatment HCV load. Interestingly, circulating sFas was upregulated when IFN- was administered at short intervals (3MU/every 12h). This upregulation was accompanied by parallel aminotransferase elevation, which was observed regardless of a virological response.Conclusions sFas elevation, in parallel with the severity of liver injury, suggests the possible upregulation of hepatic Fas expression and the Fas-mediated pathway in both HCV- and type 1 IFN-induced liver injury. The essential function of sFas to protect hepatocytes against Fas-mediated liver injury was not evident in these clinical settings.     

Increased levels of soluble Fas receptor and Fas ligand in the cerebrospinal fluid of HIV-infected patients

Analyses of serum samples and blood cells have revealed a dysregulation of the Fas/Fas ligand (FasL) system during HIV infection, which may be related to disease progression. As Fas and FasL have been suggested to participate in brain injury in a variety of CNS disorders, the aim of this study was to determine (1) whether soluble Fas and FasL can be detected in cerebrospinal fluid (CSF) samples from HIV-infected patients, (2) whether levels of these molecules are related to disease progression, and (3) whether levels of sFasL are related to other laboratory findings. Soluble Fas was detected in 38 of 56 (68%) and soluble Fas ligand in 17 of 56 (30%) CSF samples from HIV-infected patients. CSF levels of both molecules correlated neither with the CSF-to-serum albumin ratio nor with corresponding serum concentrations. This finding suggests that they are at least in part produced intrathecally. Levels of both CSF sFas and sFasL correlated significantly and inversely with the blood CD4+ cell counts, suggesting that the intrathecal release of both molecules is increased during progression to advanced immunodeficiency.     

慢性心力衰竭患者的血清可溶性Fas配体和可溶性Fas受体

目的 分析血清可溶性Fas配体(sFasL)和可溶性Fas受体(sEas)与慢性心力衰竭(CHF)的相关性。方法采用酶联免疫吸附双抗体夹心法检测33例CHF患者(CHF组,心功能Ⅱ-Ⅳ级,NYHA)血清sFasL和sFas浓度,并与18例心功能Ⅰ级(NYHA)组比较。结果 CHF与心功能Ⅰ级间sFasL浓度无显著统计学差异[231.50±84.50(心功能Ⅱ级216.50±96.00,Ⅲ级226.80±85.70,Ⅳ级244.00±73.00)vs217.50±89.00pg/mL,P>0.05]。而CHF组血清sFas浓度显著高于心功能Ⅰ级组[1353.30±507.71(心功能Ⅱ级1154.85±371.20,Ⅲ级1412.88±493.62,Ⅳ级1875.67±806.10)vs983.11±461.26pg/mL,P<0.05]。结论 血清sFasL与CHF无相关性。而血清sFas与CHF存在显著相关性。且sFas浓度增高的程度与CHF的严重程度相平行,sFas浓度增高可能在CHF发病机制中起重要作用。     

Circulating endothelial progenitor cell levels are higher during childhood than in adult life

Age-related vascular dysfunction contributes to the increased cardiovascular risk in elderly. Endothelial progenitor cells (EPC), a hematopoietic stem cell (HSC) subtype, can improve vascular repair. Therefore, it is hypothesized that a decrease in these circulating progenitor cells during aging plays a role in the enhanced cardiovascular risk. Until now, research has focused on EPC and HSC in the aging adult, but no studies have been conducted in children whereas animal studies specifically suggest a benefit of juvenile bone marrow. We investigated CD34(+)/KDR(+) EPC and CD34(+) HSC numbers by flow cytometry in healthy humans aged 1- to 81-years old. An inverse relation with age was observed for EPC counts [r=-0.37, p=0.007] as well as for HSC counts [r=-0.37, p=0.008]. During childhood significantly higher levels of EPC [p<0.0001] and HSC [p=0.001] were found compared to adults. These findings may have great clinical relevance since increasing circulating EPC levels is a promising therapeutic target to enhance the endogenous regenerative capacity. Better insight in the mechanisms underlying the higher EPC levels in children may provide options to increase EPC counts in adults, thereby potentiating endothelial repair mechanisms.     

Plasma adiponectin levels in newborns are higher than those in adults and positively correlated with birth weight

OBJECTIVE: The aim of this study was to examine plasma adiponectin concentrations during perinatal the period and their correlations with fetal anthropometric parameters and other hormones. DESIGN: Venous cord blood samples were obtained from 59 full-term healthy newborns (36 males and 23 females, gestational age 37.0-41.4 weeks, birth weight 2,146-4,326 g, birth length 44.0-54.5 cm). The blood samples were also obtained from 15 neonates (postnatal day 3-7) whose cord blood had already been collected and the changes in adiponectin concentrations were examined. MEASUREMENTS: The adiponectin concentration was determined by enzyme-linked immunosorbent assay. The leptin concentration was determined by radioimmunoassay. Insulin, GH and IGF-1 concentrations were determined by immunoradiometric assays. RESULTS: The plasma adiponectin concentrations in cord blood ranged from 6.0 to 55.8 microg/ml (median 22.4 microg/ml), which were much higher than those in normal-weight adults (P < 0.0001). In contrast to the findings in adults, these values were positively correlated with birth weight (r = 0.43, P = 0.0005), body mass index (r = 0.44, P = 0.0005), birth weight/birth length ratio (r = 0.46, P = 0.0002) and the leptin concentrations (r = 0.39, P = 0.004). When the effects of fat mass-related anthropometric parameters such as the birth weight/birth length ratio were controlled, plasma adiponectin concentrations had a significant inverse correlation with insulin concentrations (r = -0.35, P = 0.01). There was no significant gender difference in adiponectin concentrations among newborns. The adiponectin concentrations in neonates (postnatal day 3-7) did not change significantly compared with those in cord blood. CONCLUSIONS: In contrast to the findings in adults, these results suggest that the adiponectin concentration increases with the mass of fetal fat.     

Proinflammatory cytokines in sera of elderly patients with dementia: levels in vascular injury are higher than those of mild-moderate Alzheimer's disease patients.

Cognitive functions display a progressive impairment with ageing, and this is thought to be due to the accumulation of neuronal loss or acute and/or repeated microvascular accidents. Chronic damage to the brain cortex lead to decreasing ability of elderly subjects to cope with daily events and ultimately result in loss of self-sufficiency. Since proinflammatory cytokines have been implicated both in cerebrovascular injury due to atherosclerosis and in Alzheimer's disease (AD), we investigated 70 elderly subjects with neurocognitive and functional impairment. Diagnosis was established in 54, the others were included in the "mixed" group. Sera were collected and stored at -70 degrees C until measurement of IL-1beta and TNF-alpha, performed by commercial ELISA kits. Data obtained were analysed with respect to other socio-demographic, psychoneurological and clinical variables.The results show that serum TNF-alpha was lower in mild-moderate AD compared to severe AD and dementias due to vascular disease, as well as the TNF-alpha/IL-1beta ratio. Both cytokines showed a significant relationship with age.Our study suggests that proinflammatory cytokines serum profiles seem to discriminate between mild-moderate AD and vascular or mixed forms of dementia. Furthermore, it offers new evidence of a strong implication of inflammatory mechanisms in atherosclerosis, more than in less severe AD.     

Plasma osteopontin levels are higher in patients with primary aldosteronism than in patients with essential hypertension

BACKGROUND: The incidence of cardiovascular events is higher in patients with primary aldosteronism (PA) than in patients with essential hypertension (EHT). Aldosterone has been shown to play an important role in the development of vascular inflammation and myocardial fibrosis in animal models. Elevated serum inflammatory cytokine is an independent cardiovascular risk factor in patients with EHT. In the present study, we compared levels of inflammatory cytokines between patients with PA and EHT. METHODS: The study subjects were 15 patients with PA and 15 age-matched patients with EHT. Serum interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), high sensitive C-reactive protein (hsCRP), and plasma osteopontin (OPN) levels were measured by enzyme-linked immunosorbent assays. RESULTS: Systolic and diastolic blood pressure (BP) did not differ between the PA and EHT patient groups. Levels of serum IL-6 (P = .563), TNF-alpha (P = .480), and hsCRP (P = .870) did not differ between the two groups. In contrast, plasma OPN levels in patients with PA were significantly higher than those in patients with EHT (P < .0001). There was no relationship between BP and plasma OPN levels in patients with PA. CONCLUSIONS: The present study showed that plasma OPN levels were higher in patients with PA than in patients with EHT.     

胃癌患者血清可溶性FasL的变化及意义

应用双抗体夹心酶联免疫吸附法(ELISA)检测45例胃癌患者血清中可溶性FasL(sFasL)水平,并取30例健康献血员为对照。结果显示,胃癌患者术前血清sFasL为(15.24±1.25)μg/L,30例健康献血员sFasL病理为(4.21±1.13)μg/L。两组比较P<0.01。胃癌患者术前血清sFasL含量[(15.24±1.25)μg/L]显著高于术后(5.36±1.19)μg/L],P <0.01,且分期越高、分化程度越低、有淋巴结转移、肿瘤直径>3cm者,术前血清sFasL越高。提示胃癌患者血清中含有sFasL,且sFasL在胃癌免疫逃逸、反击机制中起重要作用;术前胃癌血清中sFasL水平可作为术后随访和判断预后的一个重要指标。     

Clinical implications of circulating soluble Fas and Fas ligand in patients with acute myocardial infarction.

BACKGROUND: Apoptotic cell death is the major form of myocardial damage produced by coronary ischemic events. OBJECTIVE: To assess whether circulating levels of soluble Fas (sFas), an inhibitor of apoptosis, and sFas ligand, an inducer of apoptosis, in patients with coronary artery disease are greater than normal. METHODS: Forty-seven patients [acute myocardial infarction (AMI) in 17, old myocardial infarction (OMI) in 15, stable angina in 15] and 10 normal control subjects participated in this study. Serum levels of sFas and sFas ligand in all patients were measured, and cardiac catheterizations were performed. RESULTS: Serum levels of sFas were greater than normal only in patients with AMI (4.6 +/- 1.6 ng/ml); the levels were significantly higher than those in patients with OMI (2.1 +/- 0.6 ng/ml) and stable angina (2.2 +/- 0.5 ng/ml), and in normal subjects (2.0 +/- 0.6 ng/ml; P < 0.0001). However, there was no difference among serum levels of sFas ligand for all groups. For patients with AMI, there was no significant correlation between serum levels of sFas and peak levels both of plasma creatine phosphokinase and of plasma myosin light chain type I as clinical indexes of infarct size. However, there were significant correlations between serum levels of sFas and both pulmonary artery wedge pressure (r = 0.767, P = 0.0003) and left ventricular end-diastolic pressure (r = 0.629, P = 0.03). CONCLUSIONS: Circulating sFas increases in concentration in relation to the severity of hemodynamic conditions in patients with AMI, but it is independent from size of infarct. Therefore, circulating sFas could play an important role as the marker of pathophysiologic conditions associated with cardiomyocyte apoptosis in AMI.     

sFas与sFasL在自身免疫疾病中的意义

目的　研究sFas与sFasL在系统性红斑狼疮 (SLE)等自身免疫疾病中的意义及抗单链DNA(ssDNA)抗体与sFas和sFasL介导凋亡的相关性。方法　采用夹心ELISA方法检测 31例SLE病人 ,32例类风湿关节炎 (RA)病人 ,2 0例 1型糖尿病 (IDDM )病人及 5例多发性硬化病 (MS)病人血清中sFas与sFasL含量及抗ssDNA抗体水平。结果　在SLE、RA、IDDM及MS患者血清中的sFas含量 (pg/ml)分别为 2 881± 16 5 3 ,988± 6 96 ,135 2± 413 ,15 40± 5 6 6 ,明显高于正常对照 (P <0 0 0 2 ) ,SLE病人sFas含量高于RA ,MS ,IDDM病人。SLE、RA患者血清sFasL含量 (pg/ml)分别为5 35± 431、12 38± 1184,明显高于正常对照 (P <0 0 2 ) ,MS、IDDM患者血清sFasL含量 (pg/ml)分别为 2 5 1± 140 ,2 11± 73 ,低于正常对照 (P >0 0 5 )。在SLE、RA病人中 ,高浓度sFasL者伴有高浓度sFas。在SLE病人中 ,所有抗ssDNA抗体阳性者均伴有高浓度sFas,所有抗sFas阴性者 ,ssDNA抗体也为阴性。结论　在SLE等疾病中sFas水平明显高于正常人 ,可作为疾病进展与治疗效果的判断指标。抗ssDNA抗体与sFas具有关联性。sFas与sFasL在疾病中的相互作用及动态变化有待进一步研究     

Elevation of soluble Fas and soluble Fas ligand in reactive macrophage activation syndromes

Derailed T-cell activation can give rise to life-threatening macrophage activation, the final common pathway of the different forms of reactive macrophage activation syndromes (rMAS). Besides inappropriate activation of the immune system, impaired termination of immune responses might be another mechanism leading to rMAS. The Fas (CD95)/Fas ligand (CD95 ligand) system functions in turning off immune responses by executing activation-induced cell death (AICD). Soluble Fas (sFas) and Fas ligand (sFasL) can interfere with their corresponding membrane-bound counterparts, qualifying them as potential parameters of impaired immune termination. Hence, sFas and sFasL were analyzed in sera of rMAS patients. We show that soluble Fas/CD95 (sFas) is elevated >2 SD over the mean of controls in all 8 rMAS episodes studied (mean 12.08 +/- 6.12 ng/mL, range 3.7-20.2; controls 2.46 +/- 0.49, range 1.5-2.9). sFasL was detected during five rMAS episodes (0.70 +/- 0.49 ng/mL, range 0.16-1.28; controls all below the limit of detection of 0.1). In addition, both parameters decrease during convalescence, reflecting clinical evolution. In conclusion, sFas seems to be consistently elevated during acute rMAS. sFasL is detected only in a subgroup of our adult rMAS patients extending the recent finding of sFasL elevation in a majority of children with macrophage activation syndromes (Hasegawa et al. Blood 1998;91(8):2793-2799). By interfering with AICD, sFas and sFasL might contribute to the pathogenesis of at least a subset of rMAS.     

Physical training modulates proinflammatory cytokines and the soluble Fas/soluble Fas ligand system in patients with chronic heart failure

OBJECTIVES: We sought to investigate the effects of physical training on circulating proinflammatory cytokines and the soluble apoptosis mediators Fas (sFas) and Fas ligand (sFasL) in patients with chronic heart failure (CHF). BACKGROUND: Recent investigations have shown an overexpression of circulating proinflammatory cytokines and soluble apoptosis mediators in patients with CHF, which may be related to their exercise intolerance and clinical deterioration. METHODS: Plasma levels of tumor necrosis factor-alpha (TNF-alpha), soluble TNF receptors I and II (sTNF-RI and sTNF-RII, respectively), interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), sFas and sFasL were measured in 24 patients with stable CHF (New York Heart Association functional class II/III; left ventricular ejection fraction 23.2 +/- 1.3%) and in 20 normal control subjects before and after a 12-week program of physical training in a randomized, crossover design. Functional status of patients with CHF was evaluated by using a cardiorespiratory exercise test to measure peak oxygen consumption (VO2max). RESULTS: Physical training produced a significant reduction in plasma levels of TNF-alpha (7.5 +/- 1.0 pg/ml vs. 4.6 +/- 0.7 pg/ml, p < 0.001), sTNF-RI (3.3 +/- 0.2 ng/ml vs. 2.7 +/- 0.2 ng/ml, p < 0.005), sTNF-RII (2.6 +/- 0.2 ng/ml vs. 2.3 +/- 0.2 ng/ml, p = 0.06), IL-6 (8.3 +/- 1.2 pg/ml vs. 5.9 +/- 0.8 pg/ml, p < 0.005), sIL-6R (34.0 +/- 3.0 ng/ml vs. 29.2 +/- 3.0 ng/ml, p < 0.01), sFas (5.5 +/- 0.7 ng/ml vs. 4.5 +/- 0.8 ng/ml, p = 0.05) and sFasL (34.9 +/- 5.0 pg/ml vs. 25.2 +/- 4.0 pg/ml, p < 0.05), as well as a significant increase in VO2max (16.3 +/- 0.7 ml/kg per min vs. 18.7 +/- 0.8 ml/kg per min, p < 0.001). Good correlations were found between a training-induced increase in VO2max and a training-induced reduction in levels of the proinflammatory cytokine TNF-alpha (r = -0.54, p < 0.01) and the apoptosis inducer sFasL (r = -0.57, p < 0.005) in patients with CHF. In contrast, no significant difference in circulating cytokines and apoptotic markers was found with physical training in normal subjects. CONCLUSIONS: Physical training reduces plasma levels of proinflammatory cytokines and the sFas/sFasL system in patients with CHF. These immunomodulatory effects may be related to the training-induced improvement in functional status of patients with CHF.     

Two cases of chronic graft-versus-host disease with elevated levels of soluble Fas ligand in serum

It has recently been shown that the Fas-Fas ligand (FasL) system may be one of the pathogeneses for acute graft-versus-host disease (GVHD), and it has been reported that serum soluble Fas ligand (sFasL) increases with the presence of acute GVHD. However, there is no report on a correlation between the Fas-FasL system and chronic GVHD. We present two cases of chronic GVHD with elevated levels of serum sFasL. Its level in each case was high at the onset of chronic GVHD, but it decreased with steroid therapy. Liver dysfunction also improved as the level of serum sFasL decreased. It appears in these cases that the Fas-FasL system was related to the pathogenesis of liver damage.     

Serum selenium levels in hemodialysis patients are significantly lower than those in healthy controls

Serum selenium levels have been thought to be decreased in hemodialysis patients; however, results of previous studies have been inconsistent. Population-based hemodialysis patients (n = 1,041) and randomly recruited healthy controls (n = 384) were enrolled. Serum selenium levels were determined by inductively coupled plasma mass spectrometry and compared in hemodialysis patients and controls using analysis of covariance after adjustment for confounding factors with p < 0.1 as the result of the multiple regression analysis. Age, serum albumin levels, hsCRP levels, LDLC levels, HDLC levels, regular drinking habit and hemodialysis treatment were significantly associated with serum selenium levels in multiple regression analysis. Multivariate-adjusted means (95% CIs) of serum selenium levels were 103 μg/l (101-105) in hemodialysis patients and 117 μg/l (114-121) in controls. Selenium levels in hemodialysis patients were decreased. Whether decreased serum selenium levels contribute to increased risks for morbidity and mortality in hemodialysis patients should be examined.     

An aggressive nasal lymphoma accompanied by high levels of soluble Fas ligand

Fas ligand (FasL), either in the membrane bound form or soluble form, has cytotoxic activity against Fas-expressing cells. We report a case of nasal lymphoma accompanied by liver damage and pancytopenia. The serum level of soluble FasL (sFasL) was very high on admission, but rapidly decreased to normal levels after chemotherapy for lymphoma. Liver damage and pancytopenia also improved with the decrease in serum sFasL. Since Fas is expressed on both hepatocytes and haemopoietic cells, these facts suggest that FasL was expressed on lymphoma cells and directly associated with pathogenesis of liver damage and pancytopenia through its cytotoxic activity.