The detection of autoantibodies to ATP-binding cassette transporter A1 and its role in the pathogenesis of atherosclerosis in patients with systemic lupus erythematosus

ObjectivesTo investigate the prevalence of autoantibodies against ATP-binding cassette transporter A1 (ABCA1) in SLE patients, and evaluate the association between anti-ABCA1 autoantibodies and atherosclerosis in SLE.Design and methodsThe sera of 75 SLE patients and 75 healthy controls were tested by immunoblotting. Then, we examined the effect of anti-ABCA1 autoantibodies on cholesterol efflux in vitro.ResultsThe prevalence of anti-ABCA1 antibodies in SLE patients was significantly higher than the controls (p < 0.05). The prevalence in the SLE-plaque group was higher than that in the SLE-non-plaque group (p < 0.05). The IgG purified from anti-ABCA1-antibody positive sera can inhibit cellular cholesterol efflux from THP-1 cells in vitro with a significantly higher inhibition ratio than that of the healthy controls.ConclusionsOur observations suggest that anti-ABCA1 autoantibodies are involved in the pathogenesis of lupus atherosclerosis and that autoantibodies against ABCA1 may act as biomarkers for atherosclerosis in SLE.     

Serum soluble Fas levels in patients with autoimmune rheumatic diseases

Objective:The role of the serum soluble Fas (sFAS) system is unclear in diagnosis of several autoimmune rheumatic diseases although there are present contradictory reports on the levels of serum sFas. We therefore assessed levels of sFAS in serum of patients with autoimmune rheumatic diseases.Patients and methods:We analyzed sFas levels and their relationship to clinical and laboratory data in patients with systemic lupus erythematosus (SLE, n = 32), rheumatoid arthritis (RA, n = 28), Sjögren's syndrome (SS, n = 20) systemic sclerosis (SSc, n = 21), polymyositis/dermatomyositis (PM/DM, n = 15). Patients with osteoarthritis (OA, n = 20) and healthy volunteers (n = 20) were used as controls. Serum levels of sFAS were determined by ELISA. sFas levels greater than mean (normals) + 2 SD were considered as elevated.Results:The mean sFas values were found higher in RA, PM/DM and OA than in control although no differences were found in SSc and SS patients. The mean sFas levels in SLE patients were lower than healthy controls. Elevated sFas rates in RA, PM/DM and SS were found to be 21.4%, 60%, 10% higher than in healthy controls, respectively. sFas levels in SLE and SSc did not differ from control values. Mean sFas levels did not show significant difference between active and inactive patients in all disease groups except PM/DM, RA and OA. No correlations of sFas with relevant disease subsets, laboratory findings and treatment modalities were found.Conclusions:The findings indicate that the serum sFas molecule may provide a useful additional marker for presence and assessment of disease in patients with RA and PM/DM.     

Salivary zinc finger protein 510 peptide as a novel biomarker for detection of oral squamous cell carcinoma in early stages

BackgroundOral squamous cell carcinoma (OSCC) is one of the most frequent malignancies worldwide. Early diagnosis can mean adequate treatment and increase survival.MethodsThis study uses ClinProt technique to identify salivary biomarkers for early diagnosis of OSCC. A total of 77 salivary samples from both OSCC patients (n = 47) and healthy donors (n = 30) were analyzed with MALDI-TOF MS technology.ResultsSalivary peptides from OSCC patients were separated, using C8-functionalized magnetic beads. Three signals (2918.57 Da, 5592.64 Da, and 4372.66 Da) distinguished OSCC patients from controls. Among them, unique peptide 2918.57 Da, identified as a 24-mer peptide of zinc finger protein 510 (ZNF510), was found in 0% of saliva from healthy individuals, versus 25.0% and 60% from OSCC patients with T1 + T2 and T3 + T4 stages, respectively (P < 0.001). ELISA analysis with rabbit anti-ZNF510 peptide sera shows a starkly higher 24-mer ZNF510 peptide level in saliva from OSCC patients than that in controls (P < 0.001). Also, in immunohistochemical analysis of oral tissues, a significantly higher level of ZNF510 was observed in OSCC tissues than in the OSCC free control tissues. Analysis of areas under receiver-operating characteristic (ROC) curves in OSCC early (T1 + T2) and late stages (T3 + T4) shows greater than 0.95.ConclusionsIdentifying 24-mer ZNF510 peptide as OSCC-related salivary biomarkers via proteomic approach proved useful in adjunct diagnosis for early detection rather than specific diagnosis marker for progression of OSCC patients.     

Natriuretic peptide precursor B gene (TTTC)(n) microsatellite polymorphism in pre-eclampsia

BackgroundThere is a variable tandem repeat polymorphism in the 5′-flanking region of the natriuretic peptide precursor B gene (NPPB). A previous study showed association of the (TTTC) small tandem repeat (STR) variants of this gene and essential hypertension. Our aim was to identify this polymorphism in samples of pre-eclamptic patients and healthy controls. We also compared the natriuretic peptide B (BNP) concentrations.MethodsBlood samples were collected from healthy pregnant normotensive women (n = 235) and women with pre-eclampsia (n = 220). DNA was isolated and fluorescent PCR and DNA fragment analysis was performed for the detection of (TTTC) repeats. The plasma BNP concentration was measured by fluorescence immunoassay method.ResultsWe detected 12 different (TTTC) repeats on the NPPB gene in the studied population. The overall distribution of alleles and genotypes was significantly different between the control and pre-eclamptic groups. The number of 10-repeat genotype carriers showed significantly lower frequency in pre-eclamptics than in the healthy pregnant controls (p = 0.032). After adjustment for confounding factors pre-pregnancy BMI, maternal age, primiparity and smoking, the calculated odds ratio (OR) was 0.19 (95% CI: 0.04–0.87). Similarly, the 12-repeat genotype carriers showed significantly lower frequency in pre-eclamptics than in the healthy pregnants (p = 0.037; adjusted OR: 0.53 (95% CI: 0.29–0.96)). In contrast the 11-repeat genotype carrier frequency was significantly higher in the pre-eclamptic than in the healthy pregnant group (p < 0.001; adjusted OR 2.91 (95% CI: 1.75–4.84)).The concentration of the BNP was 9.75 pg/ml in the healthy controls and 32.40 pg/ml in the pre-eclamptic group (p < 0.0001). The 11/11 genotype carriers had significantly higher BNP levels in both groups.ConclusionsThe NPPB gene (TTTC) microsatellite polymorphism in the 5′-flanking region showed significant difference in the distribution of alleles and genotypes between healthy pregnant controls and pre-eclamptic patients in an ethnically homogeneous population. The concentration of the BNP was higher in pre-eclamptic women, and it showed association with the (TTTC) genotypes. We introduced an F-PCR and DNA fragment analysis method for the fast and reliable detection of this STR.     

Assessment of circulating proteasome chymotrypsin-like activity in plasma of patients with acute and chronic leukemias

ObjectiveWe evaluated whether the proteasomal chymotrypsin-like (ChT-L) activity is increased in plasma of patients with acute lymphoblastic (ALL), acute myeloblastic (AML) and chronic lymphocytic (CLL) leukemias.MethodsThe activity was assayed using the fluorogenic peptide substrate in the presence of an artificial activator sodium dodecyl sulfate (SDS) in the plasma of healthy donors (n = 15) and ALL (n = 15), AML (n = 28) and CLL (n = 22) patients.ResultsThe activity was significantly (P < 0.001) higher in the plasma of ALL and AML patients at the diagnosis than in healthy subjects and decreased after therapy or remained unchanged or rose during relapse. By contrast, in CLL patients at the diagnosis, the activity did not differ significantly from the healthy controls. In each group, the activity positively correlated with the serum lactic dehydrogenase activity.ConclusionsPlasma proteasome ChT-L activity can be a useful bio-marker for patients with acute leukemia at the blast stage.     

Genetic risk factors for renal failure among north Indian ESRD patients

ObjectivesAngiotensin converting enzyme (ACE), G-Protein couple receptor (G-Prot), endothelial nitric oxide synthase (ecNOS), Leptin ? 2548G/A and uncoupling protein (UCP2) are potent regulators of intra renal hemodynamics and may be the causative factors contributing to the deterioration of renal functions. In recent years few studies have been published to show the association of these markers with the end stage renal disease (ESRD). Our study was designed to see the role of different genetic factors individually and synergistically in the progression of renal failure.Design and methodsThe genotypes of these markers were determined by PCR and RFLP. The gene frequencies of ACE, G-protein, ecNOS, Leptin and UCP2 in 184 ESRD patients and 569 healthy controls from North India were compared.ResultsThere was a significant difference between ESRD patients and control groups both in the biochemical parameters and genotype frequencies. The genotype distribution of ACE in patients was significantly different from the controls (p = 0.0001; OR = 9.428; 95% CI = 4.56–19.492). There was no difference observed for the GNB3-825 TT genotype and for ecNOS aa genotype in patient and control groups. The distribution of Leptin ? 2548G/A genotype and UCP2 genotype in patients were significantly different from that of controls (p = 0.0013; OR = 2.804; 95% CI = 1.501–5.237 and p = 0.0001; OR = 8.853; 95% CI = 3.458–22.667 respectively).ConclusionsOur results propose that the ACE-DD, Leptin AA and UCP2-DD genotype may be potential genetic markers for predicting the causation and progression of chronic renal failures.     

Value of serum anti-p53 antibodies as a prognostic factor in Egyptian patients with hepatocellular carcinoma

Objectivep53 antigen is an oncoprotective antigen and when damaged, leads to production of anti-p53 and also predisposes to various cancers, including hepatocellular carcinoma (HCC). Serum anti-p53 has been proven to have a prognostic value in patients with HCC. The objective of this study was to determine the prevalence and prognostic utility of serum anti-p53 in Egyptian patients with HCC.MethodsForty one patients with HCC, 26 patients with liver cirrhosis and 29 healthy controls were included in this study. For all the studied groups, we studied the clinical data, abdominal ultrasound (US) findings, biochemical liver function tests, serum alpha-fetoprotein (AFP) levels detected by enzyme immunoassay (EIA) kit and anti-p53 antibody levels by a modified enzyme-linked immunosorbent assay (ELISA). The severity of liver disease was assessed by Child–Pugh and MELD scores. Tumor characteristics were detected by (US) with or without computed tomography (CT) scan. These characteristics included tumor size, number and site. Tumor staging was done using Okuda, Cancer Liver Italian Program (CLIP) and Tokyo staging systems. Also, the overall survival of patients with HCC with reference to p53 antibody level was studied.ResultsThe mean age of HCC patients was 57.95 ± 8.41. There was a male predominance among HCC patients with male-to-female ratio of 3.6:1. Anti-p53 antibodies were detected in the sera of 68.3% of HCC patients, 50% of liver cirrhosis patients and 17.2% of healthy control subjects. The data showed that HCC patients had a significantly higher mean anti-p53 antibody values (p = 0.0001), than both liver cirrhosis patients and healthy control groups. Our results revealed that anti-p53 has a positive significant correlation with AFP (p = 0.002), severity of liver disease [Child Pugh score (p = 0.02) and MELD score (p = 0.0003)], tumor size (p < 0.0001), tumor number (p = 0.003) and tumor staging systems [Okuda (p = 0.04), CLIP (p = 0.006) and Tokyo (p < 0.0001)]. Also, our results revealed that serum anti-p53 antibodies had a significant association with overall survival of patients with HCC (p = 0.019) with a shorter survival time in anti-p53 positive status patients and with higher anti-p53 antibody levels within 19 months follow up.ConclusionThe detection of anti-p53 antibodies may be suitable for assessing the prognosis of HCC patients. The higher percentage of positivity of anti-p53 antibodies in Egyptian control subjects than reported elsewhere needs further thorough investigation.     

Autoantibodies to GP2, the major zymogen granule membrane glycoprotein, are new markers in Crohn's disease

BackgroundCrohn's disease (CD) is an inflammatory bowel disease (IBD) characterized by reactivity against microbial and self antigens. Zymogen granule glycoprotein 2 (GP2) was identified as the major autoantigen of CD-specific pancreatic autoantibodies (PAB).MethodsHuman GP2 was expressed in the Spodoptera frugiperda 9 (Sf9) cell line using the baculovirus system, purified by Ni-chelate chromatography, and used as antigen for anti-GP2 IgA and IgG assessment by enzyme-linked immunosorbent assays (ELISA). Antibodies to mannan of Saccharomyces cerevisiae (ASCA), PAB, and anti-GP2 were investigated in sera of 178 CD patients, 100 ulcerative colitis (UC) patients, and 162 blood donors (BD).ResultsAnti-GP2 IgG and IgA were found in 48/72 (66.7%) and 23/72 (31.9%) PAB positive and 5/106 (4.7%) and 1/106 (0.9%) PAB negative CD patients (p < 0.0001), respectively. CD patients displayed significantly higher reactivity to GP2 than UC patients and BD (p < 0.0001), respectively. Occurrence of anti-GP2 antibodies correlated with PAB reactivity (Spearmen's rho = 0.493, p < 0.00001). There was a significant relationship between the occurrence of ASCA IgG and anti-GP2 IgG (p = 0.0307).ConclusionsAnti-GP2 IgG and IgA constitute novel CD specific autoantibodies, the quantification of which could improve the serological diagnosis of IBD.     

Coenzyme Q10 levels are low and associated with increased mortality in post-cardiac arrest patients

AimSurvival after cardiac arrest (CA) is limited by the profound neurologic insult from ischemia–reperfusion injury. Therapeutic options are limited. Previous data suggest a benefit of coenzyme Q₁₀ (CoQ₁₀) in post-arrest patients. We hypothesized that plasma CoQ₁₀ levels would be low after CA and associated with poorer outcomes.MethodsProspective observational study of post-arrest patients presenting to a tertiary care center. CoQ₁₀ levels were drawn 24 h after return of spontaneous circulation (ROSC) and compared to healthy controls. Levels of inflammatory cytokines and biomarkers were analyzed. Primary endpoints were survival to discharge and neurologic status at time of discharge.Results23 CA subjects and 16 healthy controls were enrolled. CoQ₁₀ levels in CA patients (0.28 μmol L^?1, inter-quartile range (IQR): 0.22–0.39) were significantly lower than in controls (0.75 μmol L^?1, IQR: 0.61–1.08, p < 0.0001). The mean CoQ₁₀ level in CA patients who died was significantly lower than in those who survived (0.27 vs 0.47 μmol L^?1, p = 0.007). There was a significant difference in median CoQ₁₀ level between patients with a good vs poor neurological outcome (0.49 μmol L^?1, IQR: 0.30–0.67 vs 0.27 μmol L^?1, IQR: 0.21–0.30, p = 0.02). CoQ₁₀ was a statistically significant predictor of poor neurologic outcome (adjusted p = 0.02) and in-hospital mortality (adjusted p = 0.026).ConclusionCoQ₁₀ levels are low in human subjects with ROSC after cardiac arrest as compared to healthy controls. CoQ₁₀ levels were lower in those who died, as well as in those with a poor neurologic outcome.     

Genetic association of rs11610206 SNP on chromosome 12q13 with late-onset Alzheimer's disease in a Han Chinese population

BackgroundSeveral genome wide screens and candidate gene studies have implicated the chromosome 12p13 locus as possibly harboring genetic variants predisposed to late-onset Alzheimer's disease (LOAD). Recently, the strongest significant association was reported for the single nucleotide polymorphism (SNP) rs11610206 on chromosome 12q13 in an independent genome-wide association study (GWAS) in Caucasians.MethodsWe investigated whether the SNP on chromosome 12q13 was associated with LOAD in a Han Chinese population. The common rs11610206 SNP on chromosome 12q13 was genotyped using MALDI-TOF mass spectrometry in 322 patients with LOAD and in 391 healthy controls matched for sex and age.ResultsPatients with LOAD had higher frequencies of T allele (56.0% versus 49.2%) compared with controls [odds ratio (OR) = 1.45, 95% confidence intervals (CI) = 1.08–1.95, and P = 0.01]. After stratification by APOE ε4-carrying status, the T allele of rs11610206 was significantly associated with LOAD only in APOE ε4 allele carriers (OR = 2.05, 95% CI = 1.21–3.47, and P = 0.007). Furthermore, multivariate logistic regression analysis showed that the TT genotype carriers demonstrated a 1.52-fold risk when compared with (TC + CC) genotype carriers (OR = 1.52, 95% CI = 1.07–2.17, and P = 0.02).ConclusionsThis study demonstrates an association of rs11610206 polymorphism locus on chromosome 12q13 with risk for LOAD in Han Chinese.     

Saliva S100B in professional sportsmen: High levels at resting conditions and increased after vigorous physical activity

BackgroundNeurological dysfunction is a key medical concern in professional sportsmen (PSM). We investigated whether saliva S100B concentrations in PSM and healthy controls are modified before and after training.MethodsWe conducted a case–control-study in 75 patients (25 PSM vs 50 controls) in which S100B saliva concentrations were expressed as absolute values and percentage of change (%) from samples drawn before (T0) and after (T1) training.ResultsNo differences (P > 0.05) between groups were found regarding clinical, monitoring and laboratory parameters. S100B both in PSM and controls was higher at T1 when compared to T0 (P < 0.01). In PSM, S100B was higher than controls (P < 0.001) at T0 and T1. S100B% at T0–T1 was higher (P < 0.001) in PSM and in controls and between PSM and controls (P < 0.001).ConclusionsIncreased saliva S100B levels in PSM before and after training suggest a paracrine/autocrine protein's role connected to stressing activity, which becomes especially evident in PSMs.     

Plasma adiponectin as an independent predictor of early death after acute intracerebral hemorrhage

BackgroundHyperadiponectinemia or hypoadiponectinemia is associated with different diseases. There is a paucity of data on circulating plasma adiponectin concentrations in human intracerebral hemorrhage (ICH). We investigated the plasma adiponectin concentrations in patients with intracerebral hemorrhage, and analyzed the correlation of adiponectin with the severity of brain injury and early mortality after ICH.MethodsThirty controls and 86 patients with acute ICH were included. Plasma samples were obtained on admission and at days 1, 2, 3, 5, and 7 after ICH. Their concentrations were measured by enzyme-linked immunosorbent assay.ResultsAfter ICH, plasma adiponectin level of the patients increased immediately within 6 h, peaked within 24 h, plateaued at day 2, and decreased gradually thereafter. It was substantially higher than that in the controls in a period of 7 days. A multivariate analysis showed plasma adiponectin level was an independent predictor for 1-week mortality (odds ratio, 1.199; 95% CI: 1.035–1.389; P = 0.015) and that it was associated with Glasgow coma scale (GCS) score (t = ? 3.596, P = 0.001) and plasma C-reactive protein level (t = 4.194, P < 0.001). A receiver operating characteristic curve identified that a plasma adiponectin level > 16.4 μg/ml predicted the 1-week mortality of patients with a sensitivity of 65.6% and a specificity of 90.7% (AUC, 0.789; 95% CI: 0.688–0.870). The predictive value of adiponectin concentration was significantly lower than that of GCS score (P = 0.007) and hematoma volume (P = 0.022). Adiponectin could not improve the predictive values of GCS score (P = 0.317) and hematoma volume (P = 0.226).ConclusionsAdiponectin is an independent indicator of early death and may play an anti-inflammatory role after intracerebral hemorrhage.     

Folate and choline metabolism gene variants and development of uterine cervical carcinoma

ObjectiveIt has been reported that aberrant DNA methylation can be associated with HPV infection and cervical tumorigenesis. The aim of this study was to evaluate the possibility that polymorphic variants of genes that may affect DNA methylation status are associated with the risk of cervical cancer in the Polish population.Design and methodEmploying PCR-RFLPs and HRM analyses, we examined the prevalence of BHMT Arg239Gln (rs3733890), MTR Asp919Gly (rs1805087), MTHFR Ala222Val (rs1801133), MTHFD1 Arg653Gln (rs2236225) and MTRR Ile22Met (rs1801394) genotypes and alleles in patients with advanced cervical cancer (n = 124) and controls (n = 168).ResultsThe odds ratio (OR) for BHMT Gln/Gln genotype was 0.433 (95% CI = 0.1780–1.054; p = 0.0602). The OR for patients having the BHMT Arg/Gln or Gln/Gln genotypes was 0.579 (95% CI = 0.3622–0.924; p = 0.0216). We also observed a significantly higher frequency of the BHMT 239Gln allele in controls than in patients, p = 0.0165. The genotype and allele frequencies of the MTR Asp919Gly, MTHFR Ala222Val, MTHFD1 Arg653Gln and MTRR Ile22Met gene variants did not display statistical differences between patients with cervical cancer and controls. We also did not find a significant association between the distribution of any genotypes or alleles and cancer characteristics.ConclusionOur results might suggest the protective role of the BHMT 239Gln variant in cervical cancer incidence.     

Atrial natriuretic peptide stability

ObjectiveAtrial natriuretic peptide (ANP) is a key regulator in the homeostasis of water excretion and has emerged as an important prognostic marker for symptomatic chronic heart failure (CHF). The stability of ANP represents a crucial factor in assessing its use as a cardiac biomarker. Accordingly, we assessed the stability of ANP in blood samples collected from healthy controls and CHF subjects for a 12 month period.MethodsBlood samples from 10 healthy controls and 12 symptomatic CHF subjects with left ventricular systolic dysfunction were drawn. Determination of plasma ANP was performed by a standardized radioimmunoassay protocol.ResultsThe ANP levels of healthy subjects were 68.5 ± 11.6 pg/mL at baseline and 69.9 ± 17.2 pg/mL at 12 months (p = 0.71). The ANP concentrations of CHF subjects were 199.25 ± 44.8 pg/mL at baseline and 197.83 ± 47.4 pg/mL at 12 months (p = 0.70) respectively.ConclusionANP is a stable molecule with no evidence of degradation when stored at ? 80 °C.     

Association between lipoprotein(a) levels, apo(a) isoforms and family history of premature CAD in young Asian Indians

ObjectivesThe purpose of this study was to explore the association between lipoprotein (a) [Lp(a)] levels, apo(a) isoforms and family history of premature coronary artery disease (CAD) in young Asian Indians.Design and methods220 patients (age < 40 years) with angiographic evidence of CAD and 160 age matched healthy controls were enrolled for the study. Thirty one percent of the patients and 17% of the controls had positive family history (PFH) of premature CAD. Plasma Lp(a) levels were determined by ELISA and apo(a) isoform size was determined using high-resolution immunoblotting method.ResultsMedian plasma Lp(a) levels were 2.5 times higher in patients as compared to controls (30 mg/dL vs 12.7 mg/dL; p < 0.05). The patient group having a heterozygous apo(a) isoform pattern showed higher Lp(a) levels as compared to the homozygous group (44.0 ± 38.7 vs 28.0 ± 26.4 mg/dL; p < 0.001). Further low molecular weight apo(a) isoforms (LMW; < 22 KIV repeats) were prevalent among CAD patients with PFH as compared to negative family history (62% vs 14%, p < 0.05) and this group had the highest Lp(a) levels. Stepwise regression analysis showed that Lp(a) levels and not the apo(a) isoform size, entered the model as significant independent predictors of CAD in young Asian Indians.ConclusionsThis study suggests that elevated Lp(a) levels confer genetic predisposition to CAD in young Asian Indians. Thus determination of Lp(a) levels along with other risk factors should be used to assess overall risk for CAD in this ethnic group.     

Diagnostic utility of anti-Saccharomyces cerevisiae antibody (ASCA) and Interferon-γ assay in the differential diagnosis of Crohn's disease and intestinal tuberculosis

BackgroundDifferential diagnosis of Crohn's disease (CD) from intestinal tuberculosis (ITB) is challenging. Anti-Saccharomyces cerevisiae antibody (ASCA) is a specific serological marker for CD and INF-gamma assay (QuantiFERON-TB gold test, QFT) is a good supplementary diagnostic tool for ITB. We evaluated the clinical usefulness of ASCA and QFT for differential diagnosis of CD from ITB in Korean adults.MethodsA total of 147 patients suspected to have ITB or CD were prospectively enrolled from 13 hospitals. ASCA IgG and IgA serum titers were measured by ELISA, and the QFT test was also performed.ResultsThirty-two of 72 (44.4%) patients with CD were ASCA positive (titer > 25 U) compared to 10 of 75 ITB patients (13.3%) and 3 of 20 healthy controls (15%) (p < 0.01). The QFT test was positive in 7 patients with CD (9.7%) and 50 patients with ITB (66.6%) (p < 0.01). In cases which ASCA positive/QFT negative, the sensitivity, specificity, positive predictive value, and negative predictive value for the diagnosis of CD were 44.4%, 96.0%, 91.4%, and 64.3%, respectively.ConclusionASCA is a useful diagnostic tool for CD in Korea, where ITB is prevalent. In particular, when ASCA is combined with QFT, effective differential diagnosis of CD from ITB is possible.     

Alu-based cell-free DNA: A potential complementary biomarker for diagnosis of colorectal cancer

ObjectivesMany patients with colorectal cancer (CRC) present with regional or widespread metastasis, partially reflecting limitations of the current screening programs. This study was aimed to find a complementary marker that can improve the diagnostic accuracy.Design and methodsConcentrations of cell-free DNA based on Alu (Alu‐based CFD) in 31 unselected CRC patients, 30 intestinal polyp patients and 92 healthy individuals were detected by branch DNA (bDNA). Concentrations of carcinoembryonic antigen (CEA) and carbohydrate antigen 19–9 (CA19-9) were detected by ARCHITECT assay.ResultsThere was significant difference in concentrations of CFD between CRC and intestinal polyp patients or healthy individuals (P < 0.0001). There was no statistically significant difference in CFD in different subgroups of CRC patients with respect to gender, age, tumor site and pathologic stage, suggesting that CFD might be an independent marker relative to CEA and CA19-9. There was a significant correlation between pathologic stage and CEA or CA19-9. Although no significant correlation was observed between pathologic stage and CFD, CFD (the area under the receiver operating characteristic curve (AUC) = 0.904) seemed to be a better indicator to distinguish CRC patients from intestinal polyp patients as compared with CEA (AUC = 0.681) or CA19-9 (AUC = 0.651). CFD was more accurate than CEA or CA19-9 in diagnosing CRC.ConclusionsCombination of CFD, CEA and CA19-9 may be a better option for the diagnosis of CRC than any of them used alone. Discrimination CRC from intestinal polyp patients with CFD and staging with CEA and CA19-9 may substantially improve the accuracy CRC diagnosis.     

Asymmetric dimethylarginine as a risk marker for early-onset ischemic stroke in Indian population

BackgroundAsymmetric dimethylarginine (ADMA), a circulating endogenous inhibitor of nitric oxide synthase, has been associated with the pathogenesis of atherosclerosis. The present study was initiated to investigate the role of ADMA as a biomarker of risk for early-onset ischemic stroke.MethodsPlasma ADMA levels were measured in 201 ischemic stroke patients aged between 15 and 50 years and 217, age and gender-matched healthy controls, by high performance liquid chromatography using pre-column derivatization with O-phthaldialdehyde.ResultsPatients with ischemic stroke had significantly higher plasma ADMA compared with the controls (1.49 vs. 0.97 μmol/l, p < 0.001). After adjustment for vascular risk factors, increased ADMA was associated with stroke (OR = 1.55, 95% CI 1.25–1.92, p < 0.001). Univariate analysis showed that ADMA was significantly associated with age, alcohol, smoking, hypertension, diabetes mellitus, low serum HDL-cholesterol and homocysteine. By multiple stepwise linear regression analysis, diabetes, HDL-cholesterol and homocysteine were found to be independent determinants of plasma ADMA.ConclusionsIncreased plasma ADMA is associated with increased risk for ischemic stroke in the young. Diabetes mellitus, HDL-cholesterol and homocysteine are independent predictors of elevation in plasma ADMA concentration.     

Identification of SEC61β and its autoantibody as biomarkers for colorectal cancer

BackgroundTo identify novel serological biomarkers for human colorectal cancer (CRC), we analyzed CRC tissues using gel-assisted digestion and isobaric tags with related and absolute quantitation (iTRAQ) labeling mass spectrometry (MS). By comparing pairs of tumor tissues and matched normal tissues, we discovered the SEC61β with expression changes 3.3-fold and a marginal statistical significance (p = 0.052) previously.MethodsSEC61β expression in CRC tissues was further analyzed by western blotting and immunohistochemistry. We next assessed the putative diagnostic value of the SEC61β autoantibody as a serum marker.ResultsUsing western blotting analysis, SEC61β expression was increased 1.9-fold in tumor tissues. Immunohistochemical analysis of 64 CRC specimens showed that SEC61β was positively detected in 64% of the tumors, but weakly or not detected in > 80% of the adjacent nontumor epithelial cells. Western blot analysis with plasma samples showed that the sensitivity and specificity of the SEC61β autoantibody from patients with CRC were 79% and 75%, respectively. Importantly, the results of the SEC61β autoantibody for early detection of colorectal cancer revealed a higher sensitivity of 77% than the carcinoembryonic antigen (CEA) assay.ConclusionsMeasurement of SEC61β autoantibody levels may provide an alternative detection indicator for CRC, particularly among early-stage patients.     

Oxidative modification of patient's plasma proteins and its role in pathogenesis of multiple sclerosis

BackgroundOxidative stress plays an important role in multiple sclerosis (MS).Objective and methodsThe present study was designed to evaluate the modifications of plasma proteins by estimation markers of oxidative/nitrosative stress: carbonyl groups and 3-nitrotyrosines (3-NT) levels in relapsing-remitting (RR) (n = 10) and secondary progressive (SP) (n = 10) clinical course of multiple sclerosis. Moreover, we estimated the level of uric acid (UA) in plasma of MS patients.ResultsCompared to controls (n = 10), the levels of carbonyl groups in plasma proteins were elevated (P < 0.0001) as well in RRMS as in SPMS. The highest concentration of 3-NT was observed in plasma proteins obtained from SPMS patients (P < 0.0005). The level of uric acid in plasma was significantly lower in RRMS (P < 0.0001) than SPMS.ConclusionThis is the first report which presented differences between SPMS and RRMS patients in 3-NT and protein carbonyl groups in plasma proteins.