血浆活性纤维连接蛋白及其降解产物在慢性阻塞性肺病中的意义

血浆活性纤维连接蛋白及其降解产物在慢性阻塞性肺病中的意义丁云红，吕雁群，郭品娥，徐德安，张建荣，张永生为探索血浆纤维连接蛋白（Ｆｎ）降解状态与慢性阻塞性肺疾病（ＣＯＰＤ）之间的关系，我们对８６例ＣＯＰＤ患者血浆活性Ｆｎ及其降解产物进行了测定。８６例均...     

慢性阻塞性肺疾病患者胶原成份改变的临床意义

采用放射免疫法测定慢性阻塞性肺疾病（ＣＯＰＤ）患者血清Ⅲ型前胶原肽（ＰⅢＰ）、透明质酸（ＨＡ）及血浆纤维结合蛋白（Ｆｎ）水平。结果表明，ＣＯＰＤ患者血清ＰⅢＰ、ＨＡ明显高于对照组，而血浆Ｆｎ则显著降低，提示ＰⅢＰ、ＨＡ及Ｆｎ在ＣＯＰＤ患者的致纤维化中具有一定作用，是反映ＣＯＰＤ肺纤维化倾向的一种敏感指标，对判断预后具有临床意义。     

宫颈癌与妇科良性疾病患者血中抗氧化指标的检测及其临床意义

检测了２７例宫颈癌、３０例宫颈炎和３０例子宫肌瘤患者的血清ＳＯＤ及其同功酶、全血ＧＳＨ－Ｐｘ、ＣＡＴ等的活性水平以及血清ＬＰＯ含量。结果表明，与健康对照组相比，宫颈癌患者血清Ｃｕ，Ｚｎ－ＳＯＤ、总－ＳＯＤ（Ｔ－ＳＯＤ）活性明显降低（Ｐ＜０．０１），ＬＰＯ含量明显增高（Ｐ＜０．０５）；宫颈炎患者血清Ｍｎ－ＳＯＤ、Ｔ－ＳＯＤ活性明显降低（Ｐ＜０．０１），全血ＧＳＨ－Ｐｘ活性与血清ＬＰＯ含量明显增高（Ｐ＜０．０１）；子宫肌瘤患者血清Ｍｎ－ＳＯＤ、Ｃｕ、Ｚｎ－ＳＯＤ、Ｔ－ＳＯＤ与全血ＧＳＨ－Ｐｘ活性均明显降低（Ｐ＜０．０１），血清ＬＰＯ含量明显增高（Ｐ＜０．０１）。可见，血清Ｔ－ＳＯＤ活性降低和ＬＰＯ含量升高是宫颈癌、宫颈炎与子宫肌瘤患者自由基代谢紊乱的共同特点，提示体内病理性氧自由基反应和脂质过氧化反应明显增强是上述患者共同的病理基础。     

多发性脑梗塞痴呆患者部分抗氧化指标检测及临床意义

检测配对设计的５４例多发性脑梗塞痴呆患者的５４例健康老年人血浆维生素Ｃ、血浆维生素Ｅ含量及血浆和红细胞超氧化物歧化酶活性、血浆和红细胞过氧化脂质、Ｅ－ＳＯＤ值均显著降低（Ｐ＜０．００１），平均Ｐ－ＬＰＯ和Ｅ－ＬＰＯ含量均显著升高；５４例患者的Ｐ－ＶＣ、Ｐ－ＶＥ含量均与Ｐ－ＳＯＤ、Ｅ－ＳＯＤ值呈直线正相关，均与Ｐ－ＬＰＯ、Ｅ－ＬＰＯ含量呈直线负相关；患者病程与Ｐ０ＶＣ、Ｐ－ＶＥ、Ｅ－ＳＯＤ值呈直线负     

脑中风与红细胞胆固醇,过氧化脂质和超氧化物歧化酶水平关系的研究

检测１０９例脑梗塞、１０５例脑出血患者和１００例健康对照者红细胞胆固醇（Ｅ－Ｃｈ）、血浆和红细胞过氧化脂质（Ｐ－ＬＰＯ、Ｅ－ＬＰＯ）含量及超氧休物歧化酶（Ｐ－ＳＯＤ、Ｅ－ＳＯＤ）活性的结果表明，与对照组比较，脑梗塞组Ｅ－Ｃｈ显著升高，脑出血组Ｅ－Ｃｈ显著降低；２患者组Ｐ－ＬＰＯ、Ｅ－ＬＰＯ显著升高，Ｐ－ＳＯＤ、Ｅ－ＳＯＤ显著降低；Ｅ－Ｃｈ与脑梗塞患者病情及Ｐ－ＬＰＯ、Ｅ－ＬＰＯ、Ｐ－ＳＯＤ、Ｅ－Ｓ     

体外反搏对急性脑梗塞患者血浆ET、MDA及SOD作用的研究

将４２例急性脑梗塞患者随机分为两组，对照组采用常规治疗，预察组在常规治疗基础上加用体外反搏（ＥＣＰ），分别于治疗前和治疗一个疗程后检测患者血浆内皮素（ＥＴ）、丙二醛（ＭＤＡ）及超氧歧化酶（ＳＯＤ）含量。结果显示，两组患者治疗后血浆ＥＴ、，ＭＤＡ含量下降，ＳＯＵ含量升高，以观察组更加明显、血浆ＥＴ与ＭＤＡ含量呈正相关，血浆ＥＴ、ＭＤＡ与ＳＯＤ含量呈负相关，认为ＥＣＰ能够降低急性脑梗塞患者血浆ＥＴ含量     

充血性心力衰竭患者血浆内在素与脂质过氧化的关系

为研究充血性心力衰竭（ＣＨＦ）时血浆内皮素与脂质过氧化的关系，我们观察了４０例ＣＨＦ患者治疗前后及不同心功能状态下血浆内皮素（ＥＴ）和丙二醛（ＭＤＡ）的变化。结果显示：ＣＨＦ患者的血浆ＥＴ及ＭＤＡ均较对照组明显增高（Ｐ＜０．０００１），且其含量均随心功能恶化而增加，治疗后血浆ＥＴ和ＭＤＡ均明显下降，其血浆ＥＴ与ＭＤＡ间呈正相关（Ｐ＜０．０５）。     

高血压患者超氧化物歧化酶,过氧化脂质与性激素的相关性

目的研究高血压患者ＳＯＤ、ＬＰＯ与性激素的相关性。方法分析１３８例中老年高血压（ＨＴ）患者的红细胞铜锌超氧化物歧化酶（Ｃｕ／Ｚｎ－ＳＯＤ）活性、血浆锰超氧化物歧化酶（Ｍｎ－ＳＯＤ）活性、血浆过氧化脂质（ＬＰＯ）含量和血清睾酮（Ｔ）、雌二醇（Ｅ２）经及上述抗经指一激素的相关关系。结果ＨＴ患者红细胞Ｃｕ／Ｚｎ－ＳＯＤ及血浆Ｍｎ－ＳＯＤ活性明显降低，血浆ＬＰＯ含理极显著增加；男性ＨＴ患者Ｔ以及血清睾酮与     

脑梗塞与红细胞胆固醇,血液超氧化物歧化酶,过氧化脂质水平…

检测１０９例脑梗塞患者和１００例对照者红细胞胆固醇（Ｅ－Ｃｈ）含量、务 和红细胞超氧化物歧化酶（Ｐ－ＳＯＤ、Ｅ－ＳＯＤ）活性及血浆和红细胞过氧化脂质（Ｐ－ＰＯ、Ｅ－ＬＰＯ）含量的结果表明，患者组Ｅ－Ｃｈ、Ｐ－ＬＰＯ、Ｅ－ＬＰＯ平均含量皆显著高于对照组（Ｐ〈０．０５－０．００１），Ｐ－ＳＯＤ、Ｅ－ＳＯＤ平均活性皆显著低于对照组（Ｐ〈０．００１）；患者病情随Ｅ－Ｃｈ含量升高而加重，呈直线相关；患者Ｅ－     

不同营养状态COPD肿瘤坏死因子-α测定及其临床意义

目的　研究肿瘤坏死因子－ α（ＴＮＦ－ α） 对慢性阻塞性肺疾病（ＣＯＰＤ） 营养状态的影响。方法　用放免法检测３５ 例不同营养状态的ＣＯＰＤ 患者急性加重期和稳定期血清ＴＮＦ－ α水平。结果　营养正常组（Ａ组） 急性加重期和稳定期ＴＮＦ－ α明显低于中度营养不良组（Ｂ组） 和重度营养不良组（Ｃ 组）（ Ｐ ＜ ０－０５, Ｐ ＜ ０－０１）;Ａ、Ｂ组急性加重期明显高于稳定期（ Ｐ＜０－０５）,而Ｃ组无显著性变化（ Ｐ＞０－０５）。结论　ＣＯＰＤ患者的营养状态与血清ＴＮＦ－ α水平有一定关系,ＴＮＦ－α增高可能导致ＣＯＰＤ患者病情加重和营养状态恶化。     

Plasma fibronectin during myocardial ischemia-reperfusion: Effects of magnesium,diltiazem, and a novel Mac-1 inhibitor

The important role of fibronectin (Fn) has been recognized in patients with ischemic heart disease. However, serial changes of Fn during both brief and prolonged ischemia-reperfusion are poorly known. Plasma Fn was measured during acute myocardial infarction (AMI) and myocardial stunning (MS), and in the absence of myocardial injury. The effects of magnesium (Mg), diltiazem, and a Mac-1 inhibitor on the level of Fn were elucidated. Forty-nine swine underwent prolonged (50 min) or brief (8 min) coronary artery occlusion followed by reperfusion, while six control animals were free of ischemia. During the AMI experiments, plasma Fn underwent a significant progressive increase. Mg or diltiazem similarly affects the plasma Fn, reducing its release during the entire reperfusion period, and did not influence the plasma Fn in the absence of myocardial injury. Contrarily, Mac-1 inhibition resulted in the Fn elevation in controls, and during the occlusion phase, with no significant effect during reperfusion. There were no changes in the plasma Fn during MS, while inhibition of Mac-1 was associated with the significant increase of Fn during ischemia-reperfusion. Ability of Mg, diltiazem, and leumedins to modulate plasma Fn level may have direct clinical implications for the use of these agents in patients with coronary artery disease. Am. J. Hematol. 57:309–314, 1998. © 1998 Wiley-Liss, Inc.     

Clinical significance of fibronectin and protease inhibitors in chronic obstructive pulmonary diseases

Plasma fibronectin (Fn) and protease inhibitors (alpha 2-macroglobulin, alpha 2-MG, antithrombin, AT-III activity and content) were measured in 74 COPD patients and 53 normal controls. It was showed: (1) Fn, alpha 2-MG. AT-III activity were considerably decreased in COPD, when compare with that of controls; (2) there is a negative correlation between the value of PaCO2, r = -0.719, P less than 0.01. It indicated that the Fn, AT-III activity and alpha 2-MG are closely correlated with the extent and degree of respiratory decompensation. Dynamic changes of these parameters are of some prognostic significance in COPD.     

Increased Ed-B fibronectin plasma levels in spondyloarthropathies: comparison with rheumatoid arthritis patients and a healthy population.

OBJECTIVE: To determine, for the first time, plasma levels of general fibronectin (Fn) and two spliced isoforms, Ed-A and Ed-B, in patients with spondyloarthropathy (SpA) in comparison with rheumatoid arthritis (RA) patients and healthy volunteers (HV). METHODS: Plasmas (EDTA) as well as clinical data, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were collected in two groups of 10 patients fulfilling the European Spondylarthropathy Study Group criteria for SpA or the 1987 American College of Rheumatology criteria for RA. Plasmas of 21 blood donors served as controls. Plasma levels of Fns were determined by using an in-house immunocapture ELISA, using monoclonal antibodies (MAbs) against general Fn and its isoforms. RESULTS: Total Fn plasma levels were significantly higher in the SpA group (mean+/-S.D.=1387+/-569 mg/l) than in the RA group (684+/-196 mg/l; P=0.02) and in HV (303+/-211 mg/l; P<0.0001). Ed-A Fn levels appeared higher in SpA (23+/-10.4 mg/l) and RA (32.5+/-16.5 mg/l) groups than in the HV group (2.8+/-0.9 mg/l; P=0.0003 and P<0.0001, respectively), without a significant difference between SpA and RA groups. Ed-B Fn levels were higher in SpA (6.9+/-2.1 mg/l) than in RA (3.2+/-1.9 mg/l; P=0. 02) and HV (1.1+/-0.8 mg/l; P=0.0003) groups. No significant correlation was observed in SpA patients between each Fn level and clinical activity, ESR or CRP levels. CONCLUSIONS: This study showed an increase in plasma levels of Fn and Ed-B Fn in SpA patients compared with RA patients and HV, which could not be attributed solely to systemic inflammation. It may be hypothesized that Ed-A and Ed-B Fn might reflect local turnover in inflamed tissues, and that Ed-B Fn might be particularly involved in the musculoskeletal inflammatory process of SpA.     

Measurements of desmosine and isodesmosine by mass spectrometry in COPD

OBJECTIVES: Application of mass spectrometry (MS) for direct measurements of desmosine (D) and isodesmosine (I) in urine, plasma, and sputum as markers of elastin degradation in patients with alpha(1)-antitrypsin deficiency (AATD) and non-AATD-related COPD. BACKGROUND: In COPD patients, the lungs undergo elastin injury, which can be monitored by measurements of D and I in body fluids as specific markers of elastin degradation using the specificity and sensitivity of MS. METHODS: Acid hydrolysis of blood plasma, 24-h urine and sputum measurements, followed by chromatographic separation for mass spectrometric analysis. RESULTS: Each patient group had levels of plasma D and I that were statistically significantly higher than those of control subjects. AATD patients had higher levels than COPD patients with normal alpha(1)-antitrypsin (AAT) levels. Twenty-four-hour urine measurements demonstrated no significant difference in total levels of D and I among control subjects and patients but showed a free (unbound) concentration of D and I in urine, which was statistically significantly higher in patients with COPD with and without AAT. The D and I levels in the sputum of patients with AATD exceeded the levels in COPD patients with normal AAT levels. CONCLUSIONS: MS allows a sensitive and specific analysis of D and I in body fluids. The quantification of D and I in sputum, along with increases of D and I in plasma and an elevated free component of D and I in urine provide indexes that characterize patients with COPD and can be followed in relation to the course of the disease and/or therapy.     

Fibronectin in acute and chronic inflammation

Recent evidence suggests that fibronectin (Fn), a high molecular weight glycoprotein, may be used as an indicator protein in rats with adjuvant-induced arthritis. Rocket immunoelectrophoresis, using purified goat anti-rat Fn, provided a specific and sensitive means of measuring plasma Fn in rats during the development of various inflammatory disease states. It was shown that normal rat plasma Fn levels of approximately 400 micrograms/ml double within 24 hours after injection of adjuvant. Plasma Fn levels in this model of chronic systemic inflammatory joint disease were tracked for more than 4 months and remained significantly higher than normal. On the other hand, a carrageenan-induced inflammatory response in the pleural cavity of rats resulted in a large local accumulation of leukocytes, but no change in plasma Fn levels. A carrageenan-induced model of acute inflammation resulted in increased paw swelling within 6 hours and enhanced plasma Fn levels within 24 hours; plasma Fn levels returned to normal within 1 week. Quantitation of plasma Fn levels in the rat may provide a useful biochemical parameter for the study of chronic systemic inflammatory diseases.     

The effect of smoking-related hyperhomocysteinemia on spirometric declines in chronic obstructive pulmonary disease in elderly Japanese

Smoking is implicated in chronic obstructive pulmonary disease (COPD) and hyperhomocysteinemia. To elucidate the role of hyperhomocysteinemia in COPD, we examined the relationship between plasma total homocysteine (tHcy) and spirometric declines in patients with COPD. We recruited 7 male never-smokers, 16 male control smokers, and 24 male patients with COPD. We investigated whether or not smoking might induce hyperhomocysteinemia in subjects predisposed to COPD, and then prospectively examined the relationship between plasma tHcy concentration and annual decline in FEV(1.0) in the COPD group. We found that plasma tHcy concentrations declined among groups in the following order: COPD group > control group > never-smoker group. Furthermore, plasma tHcy concentrations in the COPD group were significantly correlated with %FEV(1.0) (r(s) = 0.46). Also, COPD patients with severe airflow limitation showed a significant decrease in PaO2, which might be involved in the decreased tHcy in those patients. The prospective analysis revealed that plasma tHcy concentration, but not a history of smoking, were significantly correlated with the annual decline in FEV(1.0) calculated by the difference in FEV(1.0) between the first examination and an examination the following year (r(s) = 0.40). The present study suggests that smoking might increase plasma tHcy concentrations, leading to spirometric declines in subjects predisposed to COPD.     

Alternatively spliced EDA-containing fibronectin in synovial fluid as a predictor of rheumatoid joint destruction

OBJECTIVES: Fibronectin containing the EDA region (EDA(+)Fn), a molecule important for rheumatoid joint destruction, was measured in relation to the progression of joint destruction in rheumatoid arthritis (RA). METHODS: Total Fn and EDA(+)Fn were measured by ELISA, and the concentrations of Fn in plasma and synovial fluid were compared prospectively for 2 yr with the progression of joint destruction in 41 knee joints of 37 patients with RA. The extent of joint destruction was assessed by the Larsen score and joint space narrowing in X-ray films taken before and 2 yr after measurement of EDA(+)Fn. RESULTS: The concentration of synovial fluid EDA(+)Fn showed a positive correlation with the progression of joint destruction in RA (r=0.78). While total Fn in synovial fluid also showed a correlation with joint destruction (r=0.54), total Fn and EDA(+)Fn in plasma showed no correlation with joint destruction. The concentration of synovial fluid EDA(+)Fn was significantly higher in patients who underwent joint replacement after the measurement of EDA(+)Fn than in those who did not receive surgery (P<0.029). CONCLUSION: Synovial fluid EDA(+)Fn can be a predictor of subsequent joint destruction in RA.     

Diagnostic and therapeutic challenges in patients with coexistent chronic obstructive pulmonary disease and chronic heart failure.

Chronic obstructive pulmonary disease (COPD) and heart failure (CHF) are common conditions. The prevalence of COPD ranges from 20% to 30% in patients with CHF. The diagnosis of CHF can remain unsuspected in patients with COPD, because shortness of breath is attributed to COPD. Measurement of plasma B-type natriuretic peptide (BNP) levels helps to uncover unsuspected CHF in patients with COPD and clinical deterioration. Noninvasive assessment of cardiac function may be preferable to BNP to uncover unsuspected left ventricular (LV) systolic dysfunction in patients with stable COPD. Patients with COPD or CHF develop skeletal muscle alterations that are strikingly similar. Functional intolerance correlates with severity of skeletal muscle alterations but not with severity of pulmonary or cardiac impairment in COPD and CHF, respectively. Improvement of pulmonary or cardiac function does not translate into relief of functional intolerance in patients with COPD or CHF unless skeletal muscle alterations concomitantly regress. The mechanisms responsible for skeletal muscle alterations are incompletely understood in COPD and in CHF. Disuse and low-level systemic inflammation leading to protein synthesis/degradation imbalance are likely to contribute. The presence of COPD impacts on the treatment of CHF, as COPD is still viewed as a contraindication to beta-blockade. Therefore, COPD often deprives patients with CHF due to LV systolic dysfunction of the most beneficial pharmacologic intervention. A large body of data indicates that patients with COPD tolerate well selective beta-blockade that should not be denied to CHF patients with concomitant COPD.     

Diagnostic and therapeutic challenges in patients with coexistent chronic obstructive pulmonary disease and chronic heart failure

Chronic obstructive pulmonary disease (COPD) and heart failure (CHF) are common conditions. The prevalence of COPD ranges from 20% to 30% in patients with CHF. The diagnosis of CHF can remain unsuspected in patients with COPD, because shortness of breath is attributed to COPD. Measurement of plasma B-type natriuretic peptide (BNP) levels helps to uncover unsuspected CHF in patients with COPD and clinical deterioration. Noninvasive assessment of cardiac function may be preferable to BNP to uncover unsuspected left ventricular (LV) systolic dysfunction in patients with stable COPD. Patients with COPD or CHF develop skeletal muscle alterations that are strikingly similar. Functional intolerance correlates with severity of skeletal muscle alterations but not with severity of pulmonary or cardiac impairment in COPD and CHF, respectively. Improvement of pulmonary or cardiac function does not translate into relief of functional intolerance in patients with COPD or CHF unless skeletal muscle alterations concomitantly regress. The mechanisms responsible for skeletal muscle alterations are incompletely understood in COPD and in CHF. Disuse and low-level systemic inflammation leading to protein synthesis/degradation imbalance are likely to contribute. The presence of COPD impacts on the treatment of CHF, as COPD is still viewed as a contraindication to beta-blockade. Therefore, COPD often deprives patients with CHF due to LV systolic dysfunction of the most beneficial pharmacologic intervention. A large body of data indicates that patients with COPD tolerate well selective beta-blockade that should not be denied to CHF patients with concomitant COPD.     

Citrullination of fibronectin in rheumatoid arthritis synovial tissue

OBJECTIVES: Citrullination, catalysed by peptidylarginine deiminase (PAD), is the post-translational modification of peptidylarginine to citrulline, which is intimately involved in the pathogenesis of rheumatoid arthritis (RA). Fibronectin (Fn), a large glycoprotein, is expressed at high levels in arthritic joints and it mediates various physiological processes through interactions with cell-surface integrin receptors and growth factors. We investigated the citrullination of Fn and its potential contribution to the pathogenesis of RA. METHODS: We localized Fn expression and citrullination in RA synovial tissue by immunohistochemistry, immunoprecipitation and western blotting. We also determined levels of citrullinated Fn in plasma from RA patients using sandwich enzyme-linked immunosorbent assay (ELISA). After incubating Fn with rabbit skeletal muscle PAD, we examined the binding ability of citrullinated Fn to vascular endothelial growth factor (VEGF) and integrin beta1 using a solid-phase receptor binding assay as well as the effect of the citrullinated Fn on apoptosis using cultured HL-60 cells. RESULTS: Immunohistochemistry and western blotting analysis indicated that Fn formed extracellular aggregates that were specifically citrullinated in RA synovial tissue. No Fn deposits were observed in synovial tissues of osteoarthritis (OA). Sandwich ELISA detected higher levels of citrullinated Fn in plasma from patients with RA than from healthy controls or those with systemic lupus erythematosus. Following citrullination in vitro, the affinity of Fn for VEGF increased, but binding activity to integrin beta1 decreased and Fn no longer stimulated the apoptosis of monocytes induced from cultured HL-60 cells. CONCLUSIONS: Our results suggest that the citrullination of Fn is a specific event for RA synovium, although others have detected citrullinated total proteins in inflamed synovial tissue of RA and non-RA patients. Citrullination of Fn could alter interactions between Fn and its receptors and growth factors, consequently contributing to mechanisms of RA pathogenesis such as perturbed angiogenesis and apoptosis.