Obesity and the clinical use of serum GGT activity as a marker of heavy drinking

Objective. Gamma‐glutamyl transferase (GGT) is a widely used clinical marker of alcohol abuse. However, although obesity may also elevate serum GGT activities, the effects of overweight on the interpretation of GGT testing have remained poorly defined. Material and methods. GGT activities from 1147 moderate drinkers and 449 abstainers who were classified according to body mass index (BMI) were compared with those of 208 heavy drinkers admitted for detoxification. Results. GGT upper normal limits, defined based on normal weight abstainers (men 53?U/L; women 45?U/L) were lower than those based on moderate drinkers (men 68?U/L; women 50?U/L). The relative increases in GGT activities in male moderate drinkers with overweight (54%) or obesity (125%) exceeded the corresponding changes found in women (25% and 75%, respectively). The BMI‐dependent variation on the sensitivity of GGT for correctly classifying heavy drinkers ranged from 29% to 67%. The rates of false‐positive values in the subgroups from low to high BMI varied from 0% to 27%, respectively. Conclusions. The data indicate that the diagnostic value of serum GGT testing could be improved by using reference data derived from databases of abstainers with normal weight or BMI‐based categorization of reference ranges.     

Dipeptidyl peptidase activity of CD26 in serum and urine as a marker of cholestasis: experimental and clinical evidence.

Dipeptidyl peptidase IV (CD26) is a membrane-associated enzyme that is expressed on the surface of T cells and on the hepatocyte brush border. In a soluble form it is present in serum. CD26 has been implicated in the regulation of T cell activation and in the metabolism of hormones and cytokines. Dipeptidyl peptidase (DPP) activity is elevated in the urine and serum of patients with biliary atresia (BA). To clarify the role of cholestasis in the development of increased serum and urinary DPP/CD26 activity, we studied the mechanism of activity increase in experimentally induced cholestasis of CD26-deficient and wild-type rats. The clinical utility of serum and urinary DPP/CD26 activity measurements was tested in adult and pediatric patients with hepatobiliary diseases and in liver transplant recipients. The results establish CD26-associated serum DPP activity as a novel, clinically useful marker of cholestasis and demonstrate that in contrast with alkaline phosphatase levels, DPP levels do not change in metastatic bone disease. Additionally, DPP activity is useful as a urinary test of cholestasis in infants who are not receiving nephrotoxic medication.     

Serum levels of chitotriosidase as a marker of disease activity and clinical stage in sarcoidosis

BACKGROUND: Sarcoidosis is a systemic granulomatous disease characterized by T-lymphocyte activation and lymphocyte migration into involved organs, usually the lungs. The amounts of a number of biochemical markers, such as angiotensin converting enzyme (ACE) activity, increase in the serum of patients with sarcoidosis. Chitotriosidase is an enzyme secreted by activated macrophages able to catalyze the hydrolysis of both chitin and chitin-like substrates. Chitotriosidase is involved in defense against, and in degradation of chitin-containing pathogens such as fungi, nematodes, and insects. METHODS: Forty-three patients affected by chronic sarcoidosis, in active (23 patients) or inactive (20 patients) phase, were studied. Serum levels of chitotriosidase and ACE activity were evaluated and compared with those of 32 healthy subjects. Serum chitotriosidase concentration and ACE activity were also correlated with radiographic stage of disease. RESULTS: Individuals with chronic sarcoidosis have higher serum chitotriosidase concentrations and ACE activity than those of normal subjects. Sarcoidosis patients in the active phase of the disease had significantly higher chitotriosidase and ACE levels than those in the inactive phase. In contrast to serum ACE activity, a significant relationship between serum levels of chitotriosidase and the four radiographic stages of the disease was observed. CONCLUSION: Although the data need to be validated by further investigation, the observations made in this study seem to indicate that serum chitotriosidase concentrations may be a useful marker for monitoring sarcoidosis disease activity and prognosis.     

BHMT用于检测急性中毒性肝损伤的价值

目的分析甜菜碱高半胱氨酸甲基转移酶(BHMT)用于检测急性中毒性肝损伤的临床价值。方法采用ELISA法检测血清样本中的BHMT,检测样本为健康体检者血清和急性中毒患者血清。结果 ELISA法检测健康体检者血清样本300例,300例健康体检血清中BHMT的平均水平为9.02ng/mL(6.19~12.84ng/mL)。健康人群血清中BHMT水平的95%医学参考值范围为0.00~28.01ng/mL;ELISA法检测43例急性中毒患者的血清样本,经Spearman秩相关分析,提示BHMT和丙氨酸氨基转移酶(ALT)之间有较好的正相关关系(rs=0.757 62,P0.001);ELISA法检测20例肾损伤病例和20例健康体检者血清中的BHMT水平,提示肾损伤患者与健康体检者血清中BHMT水平的差异无统计学意义(P0.05)。结论健康人群血清中BHMT水平的医学参考值范围为0.00~28.01ng/mL;急性中毒患者血清中的BHMT与其对应的ALT之间有很好的正相关关系;BHMT水平的变化可能与肾损伤无关,其反映肝损伤的特异性较好,因此推测BHMT可能是更好的急性肝损伤的血清学标志物。     

Troponin-T as a serum marker for myocardial infarction

We report here our experience with serum troponin T(TnT), measured with the sandwich immunoassay introduced by Boehringer Mannheim as a marker for myocardial infarction. We assayed TnT in serial serum samples from 30 patients with time courses of serum CK, CK-MB, AST, and LD that we consider typical of acute myocardial infarction (MI). In every patient but one, TnT rose in parallel with both CK-MB and AST, but remained elevated significantly longer. The ratios of the elevations of the different markers varied from patient to patient with marked variation in the ratio of TnT to CK-MB. There appeared to be a significant association between the magnitude of that ratio with the level of ALT. J. Clin. Lab. Anal. 11:125–128, 1997. © 1997 Wiley-Liss, Inc.     

Autotaxin as a novel serum marker of liver fibrosis

BackgroundThe clinical significance of autotaxin (ATX), a key enzyme for the production of the bioactive lysophospholipid lysophosphatidic acid remains unknown. Serum ATX enzymatic activity reportedly increases in parallel with liver fibrosis and exhibits a gender difference.MethodsSerum ATX antigen level, measured easier than the activity, was evaluated as a marker of liver fibrosis in 2 cohorts of chronic liver disease caused by hepatitis C virus.ResultsIn the first cohort, serum ATX level correlated significantly with liver fibrosis stage and was the best parameter for prediction of cirrhosis with an area under the receiver operating characteristic curve (AUROC) of 0.756 in male and 0.760 in female, when compared with serum hyaluronic acid and aminotransferase-to-platelet ratio index, an established marker of liver fibrosis. In another cohort, serum ATX level correlated significantly with liver stiffness, a novel reliable marker of liver fibrosis, being the second-best parameter in male (AUROC, 0.799) and in female (AUROC, 0.876) for prediction of significant fibrosis, and the best parameter in male (AUROC, 0.863) and the third-best parameter in female (AUROC, 0.872) for prediction of cirrhosis, both of which were judged by liver stiffness.ConclusionsSerum ATX level may be a novel marker of liver fibrosis.     

Tartrate-resistant acid phosphatase isoform 5b as serum marker for osteoclastic activity

BACKGROUND: Tartrate-resistant acid phosphatase (AcP) 5b is a marker of osteoclastic activity and bone resorption. Immunoassays for serum TRAcP may lack sensitivity and specificity because of the presence of non-bone isoform 5a. The purpose of this study was to isolate the serum isoforms, quantify their disease-related expressions, and test an improved immunoassay for TRAcP 5b. METHODS: We separated TRAcP isoforms chromatographically from pooled sera of healthy, rheumatoid arthritis (RA) and endstage renal disease (ESRD) subjects. TRAcP isoforms were identified by electrophoresis and quantified by biochemical and immunochemical assays. Serum TRAcP activity in healthy, RA, and ESRD cohorts was assessed at pH 5.5 and 6.1, and compared with bone alkaline phosphatase (BAP) and N-telopeptides of type I collagen (NTx). RESULTS: TRAcP isoforms 5a and 5b were present in all sera; 5b was identical to osteoclastic TRAcP. In serum from healthy subjects, 5a accounted for 87% of the enzyme protein but only 55% of the activity. In RA, both isoforms were increased two- to threefold in protein, but their specific activities were subnormal. In ESRD, only 5b was abnormal, being increased fivefold in protein and threefold in activity. In RA sera, TRAcP activity did not correlate with either BAP or NTx. In ESRD sera, TRAcP activity correlated with BAP and NTx only when measured at pH 6.1. CONCLUSIONS: All sera contained both TRAcP isoforms 5a and 5b, but only 5b was present in bone. TRAcP isoform expression was variable in different diseases. Measurement of TRAcP activity at pH 6.1 improves the specificity of immunoassay for isoform 5b.     

Identification of pro-MMP-7 as a serum marker for renal cell carcinoma by use of proteomic analysis

BACKGROUND: No validated renal cell carcinoma (RCC) marker is known for detection of asymptomatic disease in selected populations or for prognostic purposes or treatment monitoring. We identified immunogenic proteins as tumor markers for RCC by combining conventional proteome analysis with serological screening, and we investigated the diagnostic clinical value of such markers in serum. METHODS: We studied the immunogenic protein expression profile of CAL 54, a human RCC cell line, by 2-dimensional electrophoresis combined with immunoblotting using sera from healthy donors compared with RCC patients. We developed a homogeneous, fluorescent, dual-monoclonal immunoassay for metalloproteinase 7 (MMP-7) and used it to measure MMP-7 in sera from 30 healthy donors, 30 RCC patients, and 40 control patients. RESULTS: Pro-MMP-7 (29 kDa; pI 7.7) in the CAL 54 cell line secretome was an immunogenic protein reactive with RCC patient sera but not with control sera. The concentrations of pro-MMP-7 were increased (P <0.0001) in sera of RCC patients (median 7.56 microg/L; range 3.12-30.5 microg/L) compared with healthy controls (median 2.13 microg/L; range 0.17-3.5 microg/L). Serum pro-MMP-7 had a sensitivity of 93% (95% CI 78%-99%) at a specificity of 75% (59%-87%) for RCC in the samples tested. CONCLUSION: Proteomics technology combined with serology led to the identification of serum pro-MMP-7 as a marker of RCC and represents a powerful tool in searching for candidate proteins as biomarkers.     

γ-谷氨酰转肽酶、丙氨酸转氨酶及其比值在肝癌诊断中的价值

目的探讨 (研究 )血清γ 谷氨酰转肽酶 (GGT)和GGT与丙氨酸转氨酶 (ALT)比值在原发性肝癌诊断中的价值。方法分健康对照组、肝硬化组、原发性肝癌组 ,分别测定 3组外周血清中的GGT及ALT活性 ,并计算GGT与ALT的比值。结果与健康对照组比较 ,肝硬化组和原发性肝癌组的外周血GGT及ALT活性均显著增高 (P <0 0 5 ) ;原发性肝癌组与肝硬化组比较 ,GGT活性显著增高 ,但ALT活性无显著性差别 (P >0 0 5 ) ;三组GGT与ALT比值比较 ,健康对照组与肝硬化组之间无显著性差异 ,但二组均与原发性肝癌组存在显著性差异 (P <0 0 5 )。结论外周血清中GGT活性及GGT与ALT的比值有鉴别肝硬化及原发性肝癌的价值 ,有助于临床对原发性肝癌的诊断     

Nucleosomes in serum as a marker for cell death.

The concentration of nucleosomes is elevated in blood of patients with diseases which are associated with enhanced cell death. In order to detect these circulating nucleosomes, we used the Cell Death Detection-ELISAplus (CDDE) from Roche Diagnostics (Mannheim, Germany) (details at http:\\biochem.roche.com). For its application in liquid materials we performed various modifications: we introduced a standard curve with nucleosome-rich material, which enabled direct quantification and improved comparability of the values within (CVintraassay:3.0-4.11%) and between several runs (CVinterassay:8.6-13.5%), and tested the analytical specificity of the ELISA. Because of the fast elimination of nucleosomes from circulation and their limited stability, we compared plasma and serum matrix and investigated in detail the pre-analytical handling of serum samples which can considerably influence the test results. Careless venipuncture producing hemolysis, delayed centrifugation and bacterial contamination of the blood samples led to false-positive results; delayed stabilization with EDTA and insufficient storage conditions resulted in false-negative values. At temperatures of -20 degrees C, serum samples which were treated with 10 mM EDTA were stable for at least 6 months. In order to avoid possible interfering factors, we recommend a schedule for the pre-analytical handling of the samples. As the first stage, the possible clinical application was investigated in the sera of 310 persons. Patients with solid tumors (n=220; mean=361 Arbitrary Units (AU)) had considerably higher values than healthy persons (n=50; mean=30 AU; p=0.0001) and patients with inflammatory diseases (n=40; mean= 296 AU; p=0.096). Within the group of patients with tumors, those in advanced stages (UICC 4) showed significantly higher values than those in early stages (UICC 1-3) (p=0.0004).     

血清GGT和GGT/ALT比值联合应用鉴别肝脏良恶性疾病

目的探讨血清GGT活性及GGT/ALT比值在肝脏良、恶性疾病中的鉴别诊断价值.方法采用全自动生化仪分别检测了138例肝脏良、恶性疾病患者和60例无肝病其他肿瘤患者及132例健康体检者血清GGT活性及ALT活性.结果所有肝脏良恶性疾病组血清GGT均显著高于健康对照组(P＜0.01)和无肝病其他恶性肿瘤组(P＜0.01);原发性肝癌组和肝转移癌组GGT活性均显著高于其他肝脏良性疾病组(P＜0.01或P＜0.05).病毒性肝炎组GGT/ALT比值显著低于脂肪肝组、原发性肝癌组、肝转移癌组、肝硬化组、肝血管瘤组之间均有极显著差别(P＜0.01);随着GGT阳性界值的提高,阳性率逐渐下降,但对肝脏恶性肿瘤诊断的特异性却显著提高.结论血清GGT活性和GGT/ALT比值联合应用可有效辅助鉴别肝脏良、恶性疾病.     

血清GGT和GGT／ALT比值联合应用鉴别肝脏良恶性疾病

目的：探讨血清GGT活性及GGT／ALT比值在肝脏良、恶性疾病中的鉴别诊断价值。方法：采用全自动生化仪分别检测了138例肝脏良、恶性疾病患者和60例无肝病其他肿瘤患者及132例健康体检者血清GGT活性及ALT活性。结果：所有肝脏良恶性疾病组血清GGT均显著高于健康对照组（P＜0．01）和无肝病其他恶性肿瘤组（P＜0．01）;原发性肝癌组和肝转移癌组GGT活性均显著高于其他肝脏良性疾病组（P＜0．01或P＜0．05）。病毒性肝炎组GGT／ALT比值显著低于脂肪肝组、原发性肝癌组、肝转移癌组、肝硬化组、肝血管瘤组之间均有极显著差别（P＜0．01）;随着GGT阳性界值的提高,阳性率逐渐下降,但对肝脏恶性肿瘤诊断的特异性却显著提高。结论：血清GGT活性和GGT／ALT比值联合应用可有效辅助鉴别肝脏良、恶性疾病。     

Evaluation of serum laminin as a tumor marker in breast cancer

Laminin is a noncollagenous constituent of the extracellular matrix (basement membrane). Increased serum concentrations were recorded in patients with a variety of cancers. The clinical usefulness of serum laminin as a marker for breast cancer was investigated in 60 female patients with malignant breast tumors (30 metastatic, 30 non-metastatic). Subjectively healthy age-matched women (n = 30) served as a control group. Laminin was significantly higher in breast cancer patients than in normal controls. Serum laminin levels were also significantly higher in patients with metastasis than in those without metastasis. A positive correlation was observed between serum laminin and the breast cancer-associated antigen CA 15-3 in the tumor patients. The sensitivity and specificity values of laminin for cancer detection at the optimum decision level [mean + 2 SD (1.4 U/ml)] were 75% and 97% respectively, with a 98% positive predictive value, 66% negative predictive value, and 82% diagnostic efficiency. For the detection of metastasis, serum laminin exhibited 77% sensitivity and 100% specificity [best decision level: mean + 2 SD (1.9 U/ml)], with a 100% positive predictive value, 81% negative predictive value, and 88% diagnostic efficiency. The latter specificity and positive predictive value were superior to those obtained with serum CA 15-3. These results suggest that serum determination of laminin could be a useful diagnostic tool in breast cancer and a valuable parameter in the prediction of metastasis.     

Unconjugated serum bile acids as a marker of small intestinal bacterial overgrowth

Non-invasive methods to detect small intestinal bacterial overgrowth often lack specificity in patients who have undergone an ileal resection or have an accelerated intestinal transit. Since elevated serum unconjugated bile acid levels have been found in patients with clinical signs of bacterial overgrowth, we studied the clinical value of unconjugated serum bile acids as a marker of small intestinal bacterial overgrowth. Patients with culture-proven bacterial overgrowth had significantly elevated fasting unconjugated serum bile acid levels (median and range: 4.5; 1.4-21.5 mumol l-1) as compared to healthy subjects (0.9; 0.3-1.7 mumol l-1, P less than 0.005), to persons with an accelerated intestinal transit (1.0; 0.3-1.9 mumol l-1, P less than 0.005) and to persons who have undergone an ileal resection (2.1; 0.7-3.6 mumol l-1, P less than 0.005). The same was true 30 and 60 min after ingestion of a Lundh meal. Serum unconjugated bile acid levels above 4 mumol l-1 were found in eight of 10 patients with culture-proven small intestinal bacterial overgrowth whereas serum levels above 4 mumol l-1 were found in none of the patients from the three control groups. These results suggest that determination of unconjugated serum bile acids is of clinical value in the evaluation of patients suspected of small intestine bacterial overgrowth.