Useful Biomarkers (useful + biomarker)

Distribution by Scientific Domains
Distribution within Medical Sciences

Selected Abstracts

Promising Diagnostic Biomarkers for Primary Biliary Cirrhosis Identified With Magnetic Beads and MALDI-TOF-MS

Yong-Zhe Li
Abstract (PBC) is not a rare disease worldwide. Most patients are diagnosed at the advanced stage, primarily because there are not yet any valid biomarkers available for early diagnosis. Useful biomarkers are absolutely necessary for early detection of PBC. Fortunately, the use of MALDI-TOF-MS and pattern recognition software has been successful in finding specific markers for the early detection of the disease. To screen for potential protein biomarkers in the serum for diagnosing PBC, MALDI-TOF-MS combined with magnetic beads and pattern recognition software was used to investigate 119 serum samples from 44 patients with PBC, 32 controls with other hepatic disease, and 43 healthy controls. A total of 69 discriminant m/z peaks were identified as being associated with PBC. Of them, the m/z peaks at 3445, 4260, 8133, and 16,290 were used to construct a model for the diagnosis of PBC. This diagnostic model can distinguish PBC from non-PBC controls with a sensitivity of 93.3% and a specificity of 95.1%. In our blind test, it demonstrated good sensitivity and specificity: 92.9% and 82.4%, respectively. These results indicate that useful serum biomarkers for PBC can be discovered by MALDI-TOF-MS combined with the use of magnetic beads and pattern recognition software. The pattern of multiple markers provides a powerful and reliable diagnostic method for PBC with high sensitivity and specificity. Anat Rec, 292:455,460, 2009. © 2009 Wiley-Liss, Inc. [source]

Microbiotic crusts as biomarkers for surface stability and wetness duration in the Negev Desert

Giora J. Kidron
Abstract Microbiotic crusts play an important role in arid and semi-arid regions. Yet, very little information exists regarding the factors that impact their development. In an attempt to assess the main factors that may determine their growth, measurements of the amount of fines (silt and clay), rain, moisture content, wetness duration and wind erosion and deposition were carried out along a 12 station transect within a partially crusted dune field in the western Negev Desert and compared to the crust cover and chlorophyll content. Surface stability was the only variable that exhibited significant relationship with crust cover while daylight wetness duration exhibited strong positive relationship (r2 = 0·92,0·99) with the crust's chlorophyll content. The data point out that microbiotic crusts may serve as a useful biomarker for surface stability. While wetness duration and wind will control crust cover and the crust chlorophyll content in semi-stable habitats (with absolute annual change in sand level of 2,3 mm), stable habitats (absolute change <1 mm) will be controlled primarily by moisture, while habitats with low surface stability (absolute change of tens and hundreds of millimeters) will be primarily controlled by wind. Furthermore, owing to the strong positive relationship between daylight wetness duration and the crust's chlorophyll content, the crust may serve as a useful biomarker for the quantification of surface wetness duration. Copyright © 2009 John Wiley & Sons, Ltd. [source]

Human neutrophil peptides 1,3 are useful biomarkers in patients with active ulcerative colitis

Shuji Kanmura MD
Abstract Background: A specific useful biomarker for diagnosing ulcerative colitis (UC) has not yet been described. This study employed proteomics to identify serum protein biomarkers for UC. Methods: Ninety-four blood samples were isolated from patients and controls (including 48 UC, 22 Crohn's disease [CD], 5 colorectal cancer, and 6 infectious colitis patients and 13 healthy subjects). Serum samples were analyzed using the SELDI-TOF/MS ProteinChip system. After applying the samples to ProteinChip arrays, we assessed differences in the proteomes using Ciphergen ProteinChip software and identified candidate proteins, which were then characterized in immunoassays. Results: Preliminary analysis using the ProteinChip system revealed significant peak-intensity differences for 27 serum proteins between 11 patients with UC and 7 healthy subjects. Among these proteins, 3 proteins (with mass/charge ratios of approximately 3400) were identified as human neutrophil peptides 1,3 (HNP 1,3). The presence of HNP 1,3 in the patient sera was confirmed using immunoassays. Enzyme-linked immunosorbent assays demonstrated that the mean plasma concentration of HNP 1,3 was significantly higher in patients with active UC (n = 28) than in patients whose UC was in remission (n = 20) or patients with CD (n = 22), infectious colitis, or healthy subjects, and tended to be higher than in patients with colon cancer. In addition, the plasma concentration of HNP 1,3 in patients that responded to corticosteroids-based therapy decreased after treatment, whereas it was not changed in nonresponders. Conclusions: HNP 1,3 is a novel biomarker that may be useful for diagnosing patients with active UC and predicting treatment outcomes. (Inflamm Bowel Dis 2008) [source]

p63 in prostate biology and pathology

Chiara Grisanzio
Abstract The identification of stem cells and differentiation programs regulating the development and maintenance of the normal prostate epithelium is essential for the identification of the cell type(s) and molecular alterations involved in the development and propagation of prostate cancer (CaP). The p53-homologue p63 is highly expressed in normal prostate basal cells and is a clinically useful biomarker for the diagnosis of CaP. Importantly, p63 has been shown to play a critical role in prostate development. Recent experimental evidence also suggests that this gene is essential for normal stem cell function in the prostate as well as other epithelial organs. Future studies aimed at better defining the role of p63 in the renewal of the adult prostate epithelium are likely to shed new light on the mechanisms involved in prostate carcinogenesis. J. Cell. Biochem. 103: 1354,1368, 2008. © 2007 Wiley-Liss, Inc. [source]

Insights into electromagnetic interaction mechanisms

Reba Goodman
Low frequency (<,300 Hz) electromagnetic (EM) fields induce biological changes that include effects ranging from increased enzyme reaction rates to increased transcript levels for specific genes. The induction of stress gene HSP70 expression by exposure to EM fields provides insight into how EM fields interact with cells and tissues. Insights into the mechanism(s) are also provided by examination of the interaction of EM fields with moving charges and their influence on enzyme reaction rates in cell-free systems. Biological studies with in vitro model systems have focused, in general, on the nature of the signal transduction pathways involved in response to EM fields. It is likely, however, that EM fields also interact directly with electrons in DNA to stimulate biosynthesis. Identification of an EM field-sensitive DNA sequence in the heat shock 70 (HSP70) promoter, points to the application of EM fields in two biomedical applications: cytoprotection and gene therapy. EM field induction of the stress protein hsp70 may also provide a useful biomarker for establishing a science-based safety standard for the design of cell phones and their transmission towers. © 2002 Wiley-Liss, Inc. [source]

Preoperative plasma osteopontin level as a biomarker complementary to carbohydrate antigen 125 in predicting ovarian cancer

Mitsuhiro Nakae
Abstract Aim:, New biomarkers other than carbohydrate antigen (CA) 125 are needed for the detection of ovarian cancer. Osteopontin (OPN) is one of the candidates identified by high-throughput complementary DNA microarray techniques. We evaluated the preoperative plasma OPN level as a diagnostic biomarker for ovarian cancer in comparison with CA125. Methods:, Preoperative plasma OPN and CA125 levels were measured and compared in 32 patients with ovarian cancer, 34 patients with benign ovarian tumor, 30 patients with other gynecologic cancers and 31 healthy women. Preoperative plasma OPN levels were also assessed according to tumor stage, the volume of ascites and histological types. The sensitivity and specificity for predicting ovarian cancer was compared between OPN and CA125. Results:, Preoperative plasma OPN levels were significantly higher in patients with ovarian cancer than in those with benign ovarian tumor, in other gynecologic patients or in healthy women. Stage IV ovarian cancer patients and ovarian cancer patients with ascites had higher plasma OPN levels than those without ascites and in a lower stage. There was no relation between OPN and the histological type. The sensitivity of preoperative plasma OPN in detecting ovarian cancer was 81.3% and almost reached that of CA125. The specificity was moderate. Sensitivity increased to 93.8% with the combination of CA125, compared to 84.4% with CA125 alone. Conclusion:, Preoperative OPN is a useful biomarker for predicting ovarian cancer. It is especially useful when used complementary to CA125. Larger studies of patients with ovarian cancer showing a low CA125 level or in early stages of ovarian cancer are needed. [source]

Transforming growth factor ,1 (TGF,1) expression in head and neck squamous cell carcinoma patients as related to prognosis

Angela F. Logullo
Abstract Background:, Transforming growth factor ,1 (TGF,1) is a negative growth regulator in keratinocytes, and in vitro studies lead to the concept that loss of TGF,1 responsiveness is a critical step in epithelial carcinogenesis. Objective:, To investigate the prognostic relevance of TGF,1 expression in head and neck squamous cell carcinoma (HNSCC). Materials and methods:, TGF,1 distribution was determined by immunohistochemistry in oral cavity/oropharynx (n = 79), larynx (n = 36) and hypopharynx (n = 25) tumors and in matched normal adjacent mucosa. TGF,-type I and II receptors were determined in 20 cases of differentiated oral cavity/hypopharynx tumors. Cases were considered positive if displaying reactivity in >10% of the cells. Results:, TGF,1-positive expression was found in 47.2% of larynx, 36.7% of oral cavity/oropharynx and in 24% of the hypopharynx tumors. Reactivity in >60% of the cells was displayed only by 11.4% of HNSCC. All normal controls were positive. TGF,1-positive expression did not correlate with clinico pathological parameters. An association with differentiation was verified only in oral cavity/oropharynx tumors (P , 0.001). TGF,1 was also not related to 5 years survival (Kaplan,Meier). Strong and diffuse expression of TGF,-RII was identified in 19/20 cases regardless of TGF,1 immunoreactivity. Out of 17 TGF,1-positive oral cavity/oropharynx tumors, only nine expressed TGF,-RI suggesting a disruption of the TGF,1 pathway. We conclude that TGF,1 protein immunostaining is not a useful biomarker in assessment of prognosis in HNSCC. [source]

Novel Biomarkers for Diagnosis and Therapeutic Assessment of Overactive Bladder: Urinary Nerve Growth Factor and Detrusor Wall Thickness

LUTS, Issue 2009
Hann-Chorng KUO
Clinical diagnosis of overactive bladder (OAB) varies greatly and is based on subjective symptoms. A better way to diagnose and assess therapeutic outcome in patients who present with OAB needs to be developed. Evidence has shown that urinary proteins, such as nerve growth factor (NGF) and prostaglandin E2 (PGE2) levels increase in patients with OAB, bladder outlet obstruction (BOO) and detrusor overactivity (DO). Urinary NGF level increases physiologically in normal subjects at urge to void, but increases pathologically in OAB patients at small bladder volume and at urgency sensation. Patients with OAB dry and OAB wet have significantly higher urinary NGF levels compared to controls and patients with increased bladder sensation. Urinary NGF levels decrease after antimuscarinic therapy and further decrease after detrusor botulinum toxin injections in refractory OAB. A higher urinary NGF level could be a biomarker for sensory nerve-mediated DO. Urinary NGF levels could be a potential biomarker for diagnosis of OAB and serve for the assessment of the therapeutic effect of antimuscarinic therapy. Another potential biomarker for the diagnosis of OAB is detrusor wall thickness. It has been hypothesized that the bladder wall increases in thickness in patients with OAB. The thickened detrusor wall might decrease in response to antimuscarinic treatment, and measurement of detrusor wall thickness might be a useful biomarker for the evaluation of OAB. However, current investigations do not yet provide a uniform observation among various studies. [source]

Regulation of PSA secretion and survival signaling by calcium-independent phopholipase A2, in prostate cancer cells

THE PROSTATE, Issue 12 2009
Thomas M. Nicotera
Abstract BACKGROUND Serum prostate specific antigen (PSA) levels in prostate cancer patients serve as a useful biomarker for diagnosing and monitoring prostate cancer. Recently, secreted PSA has been characterized as an autocrine survival factor through activation of Akt and induction of AR. In the normal prostate, PSA is secreted in the lumen of prostatic ducts to lyse proteins in the seminal coagulum. METHODS However, the mechanism for constitutive PSA secretion from benign prostate and its transport across the prostate-blood barrier into serum are unknown. Regulation of peptide secretion by iPLA2 -, has been reported in non-prostatic tissue and in prostate tissue iPLA2 -, is reported to be under androgen regulation. We investigated whether iPLA2 plays a role for in PSA secretion by comparing iPLA2 activity and expression in normal prostate epithelial RWPE-1 cells and in LNCaP prostate cancer cells. Expression of the two active iPLA2 -, mRNA splice variants, LH-iPLA2 and SH-iPLA2, were increased and the inhibitory ankyrin-iPLA2 isoform was markedly reduced in LNCaP cells as compared to normal prostate epithelial RWPE-1 cells. RESULTS These changes are consistent with a higher enzymatic activity in LNCaP cells. The iPLA2 -,-specific inhibitor BEL inhibited PSA secretion and induced apoptosis in LNCaP cells. iPLA2 knockdown using SiRNA inhibited PSA secretion, downregulated AR and induced apoptosis. Exogenous PSA suppressed BEL-induced apoptosis and neutralizing anti-PSA antibody blocked the survival effect of PSA. CONCLUSIONS These data indicate that iPLA2 -, participates in regulating PSA secretion and supports the concept that secreted PSA provides an autocrine survival function in LNCaP cells. Prostate 69:1270,1280, 2009. © 2009 Wiley-Liss, Inc. [source]

Cerebrospinal fluid sulfatide is decreased in subjects with incipient dementia

Xianlin Han PhD
We recently noted a profound decline in brain sulfatides (ST) in subjects who died with incipient dementia due to Alzheimer's disease. Herein, we measured ST levels in cerebrospinal fluid in cognitively normal elderly and in subjects with mild cognitive impairment due to incipient demenia of the Alzheimer type. There was a significant decrease in cerebrospinal fluid ST and in the ST to phosphatidylinositol ratio in MCI subjects. The ST to phosphatidylinositol ratio accurately differentiated very mildly impaired subjects from controls on an individual basis. The cerebrospinal fluid ST to phosphatidylinositol ratio may be a very useful biomarker for the earliest clinical stage of Alzheimer's disease. Ann Neurol 2003;54:115,119 [source]

Follistatin-like protein 1 is a mesenchyme-derived inflammatory protein and may represent a biomarker for systemic-onset juvenile rheumatoid arthritis,

David C. Wilson
Objective To examine both the source of follistatin-like protein 1 (FSTL-1) and the factors that induce its expression in arthritis, and to determine whether juvenile rheumatoid arthritis (JRA) is characterized by overexpression of FSTL-1. Methods FSTL-1 expression patterns were analyzed by immunohistochemical staining of joint tissue derived from mice with collagen-induced arthritis. Induction of FSTL-1 secretion was assessed in osteoblasts, adipocytes, and human fibroblast-like synoviocytes in response to transforming growth factor , (TGF,), interleukin-1, (IL-1,), tumor necrosis factor , (TNF,), and IL-6. In addition, sera and synovial fluid from children with oligoarticular, polyarticular, or systemic-onset JRA were assayed for FSTL-1 using a custom enzyme-linked immunosorbent assay. FSTL-1 concentrations in these patients were assessed for correlations with the erythrocyte sedimentation rate (ESR) and platelet count. Results Immunohistochemical staining of murine joint sections demonstrated expression of FSTL-1 in all cell types of the mesenchymal lineage, including osteocytes, chondrocytes, adipocytes, and fibroblasts. FSTL-1 could be induced in osteoblasts, adipocytes, and human fibroblast-like synoviocytes by TGF,, IL-1,, TNF,, and IL-6. The IL-1, response was significantly greater than the TNF, response (P < 0.05). In human serum and synovial fluid, only those samples from children with the systemic-onset JRA subtype had elevated concentrations of FSTL-1. The synovial fluid concentrations of FSTL-1 were 2,3-fold higher than the serum concentrations. The elevation in serum FSTL-1 concentrations seen in children with systemic-onset JRA correlated closely with elevations in the ESR and platelet count. Conclusion These findings demonstrate that the arthritic joint matrix is a major source of FSTL-1 and that IL-1, is a central mediator of FSTL-1 secretion. Furthermore, FSTL-1 may represent a useful biomarker of disease activity in systemic-onset JRA. [source]

Identification of RGS1 as a candidate biomarker for undifferentiated spondylarthritis by genome-wide expression profiling and real-time polymerase chain reaction

Jieruo Gu
Objective To compare gene expression profiles between ankylosing spondylitis (AS) and undifferentiated spondylarthritis (uSpA) patients with inflammatory low back pain. Methods Peripheral blood mononuclear cells (PBMCs) from patients with AS, patients with uSpA, and healthy subjects were screened using genome-wide microarrays, followed by validation by real-time polymerase chain reaction (PCR). Results Microarray profiling and real-time PCR assays showed only minor differences between AS patients and healthy subjects. In contrast, 20 genes were strikingly more highly expressed in uSpA patients. Regulator of G protein signaling 1 (RGS1) was identified as the most useful biomarker for distinguishing uSpA patients, and to a lesser extent AS patients, from control subjects (P = 2.3 × 10,7 and 6.7 × 10,3, respectively). These findings were verified in an independent cohort that also included patients with rheumatoid arthritis and patients with mechanical low back pain. The receiver operating characteristic area under the curve values in the first and second cohorts of uSpA patients were 0.99 and 0.93, respectively (P = 1 × 10,4). To evaluate the possible derivation of RGS1, we cultured a monocyte-derived cell line with a panel of cytokines and chemokines. RGS1 was significantly induced either by tumor necrosis factor , (TNF,) or by interleukin-17 (IL-17). Conclusion Our findings indicate that uSpA PBMCs carry strikingly more highly expressed genes compared with PBMCs from AS patients or healthy subjects, and that TNF,- and IL-17,inducible RGS1 is a potential biomarker for uSpA, and to a lesser extent for AS, with inflammatory low back pain. [source]

Platelet C4d is highly specific for systemic lupus erythematosus

Jeannine S. Navratil
Objective Complement-activation product C4d is deposited on normal erythrocytes, while abnormal levels have been observed on the surface of erythrocytes of patients with systemic lupus erythematosus (SLE). This study examines whether C4d also deposits on human platelet surfaces, and whether platelet-bound C4d may provide a biomarker for SLE. Methods We conducted a cross-sectional study of 105 patients with SLE, 115 patients with other diseases, and 100 healthy controls. Levels of C4d on the surface of platelets were examined by flow cytometry and scanning confocal microscopy. Statistical analyses were performed to determine the clinical variables associated with platelet C4d. Results Abnormal levels of platelet C4d were found to be highly specific for SLE. Platelet C4d was detected in 18% of patients with SLE, being 100% specific for a diagnosis of SLE compared with healthy controls and 98% specific for SLE compared with patients with other diseases (P < 0.0001). In addition, platelet C4d was significantly associated with positivity for lupus anticoagulant (P < 0.0001) and anticardiolipin antibodies of the IgG (P = 0.035) or the IgM (P = 0.016) isotype. Platelet C4d was also significantly associated with SLE disease activity according to the SLE Disease Activity Index (P = 0.039), low serum C4 (P = 0.046), an elevated erythrocyte sedimentation rate (P = 0.006), and abnormal levels of C4d on erythrocytes (P < 0.0001). Conclusion This observation suggests that platelet-bound C4d may be a useful biomarker for SLE and may be a clue to the pathogenic mechanisms responsible for the myriad thrombotic and vascular complications of lupus associated with antiphospholipid antibodies. [source]

Epstein,Barr virus involvement in the pathogenesis of hydroa vacciniforme: an assessment of seven adult patients with long-term follow-up

L. Verneuil
Summary Background, Hydroa vacciniforme (HV) is a chronic papulovesicular photodermatosis of childhood, with some cases persisting through adulthood. In children, the Epstein,Barr virus (EBV) has been detected in typical HV and in HV evolving into natural killer/T-cell lymphoma. No exploration of EBV infection has been performed in adult patients with HV with long-term follow-up. Objectives, To assess EBV infection systematically in blood and in experimentally photoinduced lesions in adult patients with HV. Methods, Repeated tests for EBV DNA blood load using real-time polymerase chain reaction (PCR) and serological EBV tests were performed in seven adult patients with long-term follow-up. Skin samples from phototest-induced lesions and surrounding normal skin were studied using PCR, in situ hybridization and electron microscopy. ZEBRA protein was detected using immunostaining. Thirty-five patients with other photosensitive disorders were included as controls. Results, The EBV DNA blood load was strongly positive in the seven patients with HV and negative in 34 of 35 of the patients with other photosensitive disorders (P < 0·001). The levels were higher in photosensitive patients with HV than in patients with HV in clinical remission. Ultrastructurally, viral particles were detected in lymphocytes and also in keratinocytes in three experimentally phototest-induced lesions; they were not found in the surrounding normal skin. ZEBRA protein was also detected in phototest-induced lesions, but not in the surrounding normal skin. Conclusion, EBV is involved in HV pathogenesis and persists in adult patients with HV. A positive EBV DNA load, specific to HV in the spectrum of photosensitive disorders, might be a useful biomarker in HV. [source]

Hypermethylation of FHIT as a prognostic marker in nonsmall cell lung carcinoma

CANCER, Issue 7 2004
Riichiroh Maruyama M.D.
Abstract BACKGROUND Methylation of CpG islands in the promoter and upstream coding regions has been identified as a mechanism for transcriptional inactivation of tumor suppressor genes. The purpose of the current study was to determine the correlation between the aberrant promoter methylation of multiple genes and survival in patients with nonsmall cell lung carcinoma (NSCLC). METHODS The methylation status of nine genes was determined in 124 surgically resected NSCLC cases using methylation-specific polymerase chain reaction. RESULTS The methylation frequencies of the genes tested in NSCLC specimens were 52% for E-cadherin (CDH1), 41% for RAS association domain family protein (RASSF1A), 38% for fragile histidine triad (FHIT) and adenomatous polyposis coli (APC), 27% for retinoic acid receptor beta (RAR,) and H-cadherin (CDH13), 20% for p16INK4A, 0.8% for O6 -methylguanine-DNA-methyltransferase (MGMT), and 0% for glutathione S-transferase P1 (GSTP1). The survival of the patients with FHIT methylation-positive tumors was found to be significantly shorter than that for those patients with methylation-negative tumors (P = 0.03), even in those patients with International Union Against Cancer TNM Stage I or Stage II disease (P = 0.007). In contrast, there were no significant survival differences noted between the methylation-positive and methylation-negative tumors for the other genes tested. In addition, based on multivariate analyses, FHIT methylation-positive status was found to be independently associated with poor survival (P = 0.046) and disease stage (P < 0.0001). CONCLUSIONS The results of the current study suggest that methylation of FHIT is a useful biomarker of biologically aggressive disease in patients with NSCLC. Cancer 2004;100:1472,7. © 2004 American Cancer Society. [source]

Anaphylaxis: Clinical concepts and research priorities

Simon GA Brown
Abstract Anaphylaxis is a severe immediate-type hypersensitivity reaction characterized by life-threatening upper airway obstruction bronchospasm and hypotension. Although many episodes are easy to diagnose by the combination of characteristic skin features with other organ effects, this is not always the case and a workable clinical definition of anaphylaxis and useful biomarkers of the condition have been elusive. A recently proposed consensus definition is ready for prospective validation. The cornerstones of management are the supine position, adrenaline and volume resuscitation. An intramuscular dose of adrenaline is generally recommended to initiate treatment. If additional adrenaline is required, then a controlled intravenous infusion might be more efficacious and safer than intravenous bolus administration. Additional bronchodilator treatment with continuous salbutamol and corticosteroids are used for severe and/or refractory bronchospasm. Aggressive volume resuscitation, selective vasopressors, atropine (for bradycardia), inotropes that bypass the ,-adrenoreceptor and bedside echocardiographic assessment should be considered for hypotension that is refractory to treatment. Management guidelines continue to be opinion- and consensus-based, with retrospective studies accounting for the vast majority of clinical research papers on the topic. The clinical spectrum of anaphylaxis including major disease subgroups requires clarification, and validated scoring systems and outcome measures are needed to enable good-quality prospective observational studies and randomized controlled trials. A systematic approach with multicentre collaboration is required to improve our understanding and management of this disease. [source]

Bentazon triggers the promotion of oxidative damage in the Portuguese ricefield cyanobacterium Anabaena cylindrica: Response of the antioxidant system

Victor Galhano
Abstract Rice fields are frequently exposed to environmental contamination by herbicides and cyanobacteria, as primary producers of these aquatic ecosystems, are adversely affected. Anabaena cylindrica is a cyanobacterium with a significantly widespread occurrence in Portuguese rice fields. This strain was studied throughout 72 h in laboratory conditions for its stress responses to sublethal concentrations (0.75,2 mM) of bentazon, a selective postemergence herbicide recommended for integrated weed management in rice, with special reference to oxidative stress, role of proline and intracellular antioxidant enzymes in herbicide-induced free radicals detoxification. Activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), and glutathione S -transferase (GST) increased in a time- and herbicide dose-response manner and were higher than those in the control samples after 72 h. A time- and concentration-dependent increase of malondialdehyde (MDA) levels and the enhanced cell membrane leakage following bentazon exposure are indicative of lipid peroxidation, free radicals formation, and oxidative damage, while increased amounts of SOD, CAT, APX, GST, and proline indicated their involvement in free radical scavenging mechanisms. The appreciable decline in the reduced glutathione (GSH) pool after 72 h at higher bentazon concentrations could be explained by the reduction of the NADPH-dependent glutathione reductase (GR) activity. The obtained results suggested that the alterations of antioxidant systems in A. cylindrica might be useful biomarkers of bentazon exposure. As the toxic mechanism of bentazon is a complex phenomenon, this study also adds relevant findings to explain the oxidative stress pathways of bentazon promoting oxidative stress in cyanobacteria. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2010. [source]

Haematological reference values in Spanish adolescents: the AVENA study

Javier Romeo
Abstract Objectives:, To provide reference values for haematological indices in Spanish adolescents according to age and gender. Methods:, A cross sectional study conducted in five Spanish cities was performed. Blood was drawn from a representative sample of 581 adolescents with age ranging from 13 to 17,18.5 yr. Age- and gender-specific means, standard deviations and percentiles were determined for the following parameters: total red blood cell counts (RBC), haemoglobin concentration (Hb), haematocrit percentage (Hct), mean corpuscular volume (MCV), mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, red cell distribution width and total white blood cell (WBC) counts as well as counts and percentage of neutrophils, lymphocytes, monocytes, eosinophils and basophils; platelet count (PLT), mean platelet volume and plateletcrit percentage. Results:, Younger male subjects presented lower RBC, Hb, Hct and MCV means that their older counterpart. By contrast these differences were not observed in female subjects. As expected, RBC, Hb and Hct mean values in males were found significantly higher than in girls for all studied age groups. No significant differences were observed in WBC by age and gender. PLT values gradually decreased with age, except for females aged 17,18.5 yr. Conclusion:, The present study provides reference data on the distribution of haematological indices of Spanish adolescents. These data can be useful biomarkers of the nutritional status in adolescents. [source]

Human neutrophil peptides 1,3 are useful biomarkers in patients with active ulcerative colitis

Shuji Kanmura MD
Abstract Background: A specific useful biomarker for diagnosing ulcerative colitis (UC) has not yet been described. This study employed proteomics to identify serum protein biomarkers for UC. Methods: Ninety-four blood samples were isolated from patients and controls (including 48 UC, 22 Crohn's disease [CD], 5 colorectal cancer, and 6 infectious colitis patients and 13 healthy subjects). Serum samples were analyzed using the SELDI-TOF/MS ProteinChip system. After applying the samples to ProteinChip arrays, we assessed differences in the proteomes using Ciphergen ProteinChip software and identified candidate proteins, which were then characterized in immunoassays. Results: Preliminary analysis using the ProteinChip system revealed significant peak-intensity differences for 27 serum proteins between 11 patients with UC and 7 healthy subjects. Among these proteins, 3 proteins (with mass/charge ratios of approximately 3400) were identified as human neutrophil peptides 1,3 (HNP 1,3). The presence of HNP 1,3 in the patient sera was confirmed using immunoassays. Enzyme-linked immunosorbent assays demonstrated that the mean plasma concentration of HNP 1,3 was significantly higher in patients with active UC (n = 28) than in patients whose UC was in remission (n = 20) or patients with CD (n = 22), infectious colitis, or healthy subjects, and tended to be higher than in patients with colon cancer. In addition, the plasma concentration of HNP 1,3 in patients that responded to corticosteroids-based therapy decreased after treatment, whereas it was not changed in nonresponders. Conclusions: HNP 1,3 is a novel biomarker that may be useful for diagnosing patients with active UC and predicting treatment outcomes. (Inflamm Bowel Dis 2008) [source]

Biomarkers for prostate cancer

Eddy S. Leman
Abstract The detection of prostate cancer using a blood test has by many standards changed the face of the disease. Despite this tremendous success, there are limitations attributed to the use of prostate specific antigen (PSA) as a means to screen and detect prostate cancer. PSA, as its name implies, is not specific for prostate cancer and as such is often found elevated in other prostatic diseases/symptoms associated with the aging male. Clearly, more specific marker(s) that could identify which individuals actually have prostate cancer and differentiate them from those without the disease would be of tremendous value. The search for more accurate and clinically useful biomarkers of prostate cancer has been extensive. This has focused on individual markers, as well as groups of markers. Included among these are PSA isoforms, pathological indicators and stains, nucleic acids and others. This article highlights the discovery of PSA as a first blood-based biomarker for prostate cancer detection, as well as other molecular biomarkers and their potential application in detection of the disease. J. Cell. Biochem. 108: 3,9, 2009. © 2009 Wiley-Liss, Inc. [source]

Mass spectrometric characterization of covalent modification of human serum albumin by 4-hydroxy- trans -2-nonenal

Giancarlo Aldini
Abstract Several pieces of evidence indicate that albumin modified by HNE is a promising biomarker of systemic oxidative stress and that HNE-modified albumin may contribute to the immune reactions triggered by lipid peroxidation-derived antigens. In this study, we found by HPLC analysis that HNE is rapidly quenched by human serum albumin (HSA) because of the covalent adduction to the different accessible nucleophilic residues of the protein, as demonstrated by electrospray ionization mass spectrometry (ESI-MS) direct infusion experiments (one to nine HNE adducts, depending on the molar ratio used, from 1 : 0.25 to 1 : 5 HSA : HNE). An LC-ESI-MS/MS approach was then applied to enzymatically digested HNE-modified albumin, which permitted the identification of 11 different HNE adducts, 8 Michael adducts (MA) and 3 Schiff bases (SB), involving nine nucleophilic sites, namely: His67 (MA), His146 (MA), His242 (MA), His288 (MA), His510 (MA), Lys 195 (SB), Lys 199 (MA, SB), Lys525 (MA, SB) and Cys34 (MA). The most reactive HNE-adduction site was found to be Cys34 (MA) followed by Lys199, which primarily reacts through the formation of a Schiff base, and His146, giving the corresponding HNE Michael adduct. These albumin modifications are suitable tags of HNE-adducted albumin and could be useful biomarkers of oxidative and carbonylation damage in humans. Copyright © 2006 John Wiley & Sons, Ltd. [source]


Article first published online: 24 SEP 200
Leblond, J. D.1 & Chapman, P. J.2 1Department of Biology, Middle Tennessee State University, Murfreesboro, TN 37132. 2US EPA (NHEERL), Gulf Ecology Division, 1 Sabine Island Dr., Gulf Breeze, FL 32561 Studies of the lipids of different algal species have revealed a diversity of fatty acids, sterols, and hydrocarbons, of which several are considered useful biomarkers, with potential for characterizing phytoplankton community composition. To extend this approach and characterize the lipids and lipid classes of laboratory-cultured marine dinoflagellates, a silicic acid fractionation system was developed to obtain compositional data for sterols and hydrocarbons of over forty species. In the course of this work, a neutral fraction obtained from a lipid extract of Pyrocystis lunula was found to contain an abundant quantity of a long-chain polyunsaturated hydrocarbon, along with previously reported keto-steranes. The hydrocarbon molecular weight (364) and retention time obtained by gas chromatography/mass spectrometry analysis suggested a C27 compound, which was confirmed by reduction (Adams catalyst) to give the straight chain alkane, n-heptacosane. The presence of eight double bonds was established by deuteration to give a product with molecular weight 396. While the positions of double bonds have not been established, the carbon number of this hydrocarbon and the number of double bonds strongly suggest formation by decarboxylation of the recently described, long-chain polyunsaturated C28 fatty acid shown to be a constituent of phospholipids. This hydrocarbon was not found in any other genus of the examined dinoflagellates, and appears to be one of the first identifications of a hydrocarbon in this class of algae. The function(s) of this compound in P. lunula is currently unclear. [source]

Survey of albumin purification methods for the analysis of albumin-organic toxicant adducts by liquid chromatography-electrospray ionization-tandem mass spectrometry

Carrie L. Young
Abstract HSA has been shown to react with many organic toxicants to form adducts that are useful biomarkers for exposure. Albumin isolation is an important first step for the analysis of these protein-toxicant adducts. We tested several approaches to isolate albumin from serum treated with an electrophilic organic toxicant known to form adducts with albumin, i.e., sulfur mustard agent (HD) (2,2'-dichloroethyl sulfide), in order to evaluate these techniques as purification methods. To select the most efficient isolation strategy, methods were evaluated using gel electrophoresis, total protein quantitation, and peptide-adduct identification by MS. Results suggest that the albumin-rich fractions obtained can be used to identify exposure by quantitating the albumin adducts to electrophilic organic toxicants such as HD. The HiTrap Blue HP albumin isolation system appears to display the most promising results for purifying albumin to detect HD-adducts, exhibiting high purification efficiency, satisfactory albumin recovery, promising specificity, and a higher loading capacity for serum. [source]

Precursor ion scan profiles of acylcarnitines by atmospheric pressure thermal desorption chemical ionization tandem mass spectrometry

Giuseppe Paglia
The fatty acyl esters of L-carnitine (acylcarnitines) are useful biomarkers for the diagnosis of some inborn errors of metabolism analyzed by liquid chromatography/tandem mass spectrometry. In this study the acylcarnitines were analyzed by atmospheric pressure thermal desorption chemical ionization using a commercial tandem mass spectrometer (APTDCI-MS/MS). The method is based on the precursor ion scan mode determination of underivatized acylcarnitines desorbed from samples by a hot desolvation gas flow and ionized by a corona pin discharge. During desorption/ionization step the temperature induces the degradation of acylcarnitines; nevertheless, the common fragment to all acylcarnitines [MH,59]+ is useful for analyzing their profile. APTDCI parameters, including angle of collection and incidence, gas flows and temperatures, were optimized for acylcarnitines. The experiments were performed drying 2,µL of an equimolar mixture of acylcarnitine standards on a glass slide. The specificity was evaluated by comparing product ion spectra and the precursor ion spectra of 85 m/z of acylcarnitines obtained by the APTDCI method and by electrospray ionization flow injection analysis (ESI-FIA). The method was also employed to analyze acylcarnitines extracted from a pathological dried blood spot and a control. The method enables analysis of biological samples and recognition of some acylcarnitines that are diagnostic markers of inherited metabolic diseases. The intrinsic high-throughput analysis of the ambient desorption ionization methods offers a new opportunity either for its potential application in clinical chemistry and for the expanded screening of some inborn errors of metabolism. Copyright © 2008 John Wiley & Sons, Ltd. [source]

The role of annexins in tumour development and progression,

S Mussunoor
Abstract The annexins are a super-family of closely related calcium and membrane-binding proteins. They have a diverse range of cellular functions that include vesicle trafficking, cell division, apoptosis, calcium signalling and growth regulation. Many studies have shown the annexins to be among the genes whose expression are consistently differentially altered in neoplasia. Some annexins show increased expression in specific types of tumours, while others show loss of expression. Mechanistic studies relating the changes in annexin expression to tumour cell function, particularly tumour invasion and metastasis, angiogenesis and drug resistance, are now also emerging. Changes in the expression of individual annexins are associated with particular types of tumour and hence the annexins may also be useful biomarkers in the clinic. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source]

MiR-34a attenuates paclitaxel-resistance of hormone-refractory prostate cancer PC3 cells through direct and indirect mechanisms

THE PROSTATE, Issue 14 2010
Keitaro Kojima
Abstract BACKGROUND Patients with hormone-refractory prostate cancer are treated with taxane drugs, but eventually become drug resistant. We aimed to elucidate the molecular mechanisms underlying paclitaxel resistance of hormone-refractory prostate cancer with a special focus on the roles of miR-34a and SIRT1. METHODS Paclitaxel-resistant cells (PC3PR) were generated from hormone-refractory PC3 cells. The expression levels of mRNA and miRNA were determined by reverse transcriptase PCR and those of protein were by Western blot analysis. Transfection of miRNA precursor or siRNA was performed using the liposome-mediated method. RESULTS MiR-34a over-expression and SIRT1 knockdown attenuated paclitaxel resistance of PC3PR cells. MiR-34a expression was reduced in PC3PR cells compared with PC3 cells, while the expression levels of HuR and Bcl2 as well as SIRT1 were elevated in PC3PR cells. Luciferase reporter assays revealed that both SIRT1 3,-UTR and promoter activities were higher in PC3PR cells than in PC3 cells. Introduction of miR-34a precursor into PC3PR cells resulted in decreases in HuR, Bcl2, and SIRT1 expression and inhibition of the SIRT1 3,-UTR activity. HuR knockdown reduced SIRT1 and Bcl2 expression. These results suggest that miR-34a not only directly but also indirectly via regulating HuR expression acts on the 3,-UTR of SIRT1 and Bcl2 mRNAs, thereby controlling their expression. Thus, in PC3PR cells, reduced expression of miR-34a confers paclitaxel resistance via up-regulating SIRT1 and Bcl2 expression. CONCLUSIONS MiR-34a and its downstream targets SIRT1 and Bcl2 play important roles in the development of paclitaxel resistance, all of which can be useful biomarkers and promising therapeutic targets for the drug resistance in hormone-refractory prostate cancer. Prostate 70: 1501,1512, 2010. © 2010 Wiley-Liss, Inc. [source]

Analysis of intracellular methotrexate polyglutamates in patients with juvenile idiopathic arthritis: Effect of route of administration on variability in intracellular methotrexate polyglutamate concentrations

Mara L. Becker
Objective Intracellular methotrexate (MTX) polyglutamates (MTXGlu) have been shown to be potentially useful biomarkers of clinical response in adult patients with rheumatoid arthritis. The present study was undertaken to measure intracellular MTXGlu concentrations in a cohort of patients with juvenile idiopathic arthritis (JIA) to determine the predictors of MTXGlu variability in these patients. Methods Blood samples were obtained from patients with JIA who were being treated with a stable dose of MTX for ,3 months. Clinical data were collected by chart review. Concentrations of MTXGlu1,7 in red blood cell lysates were quantitated using an innovative ion-pairing chromatography procedure, with detection by mass spectrometry. Results Patients with JIA from a single center (n = 99; mean ± SD age 117.8 ± 56.5 months, 69 female) were included in the analysis. The mean ± SD dose of MTX was 0.51 ± 0.25 mg/kg per week, with a median treatment duration of 18 months (interquartile range 3,156 months). MTX was administered subcutaneously in 66 patients (67%). Fifty-six patients (57%) had active arthritis at the time of the clinic visit. Total intracellular MTXGlu (MTXGluTOT) concentrations varied 40-fold, with a mean ± SD total concentration of 85.8 ± 48.4 nmoles/liter. Concentrations of each MTXGlu subtype (MTXGlu1,7) were measured individually and as a percentage of MTXGluTOT in each patient. MTXGlu3 was the most prominent subtype identified, comprising 42% of MTXGluTOT, and the interindividual variability in the concentration of MTXGlu3 was the most highly correlated with that of MTXGluTOT (r = 0.96). The route of MTX administration was significantly associated with MTXGlu1,5 subtypes; higher concentrations of MTXGlu1 + 2 were observed in patients receiving oral doses of MTX, whereas higher concentrations of MTXGlu3,5 were observed in patients receiving subcutaneous doses of MTX (P < 0.0001). Conclusion In this cohort of patients with JIA, the MTXGluTOT concentration varied 40-fold. Individual MTXGlu metabolites (MTXGlu1,7), which have, until now, not been previously reported in patients with JIA, were detected. The route of MTX administration contributed to the variability in concentrations of MTXGlu1,5. [source]

Expression of CD44 variant isoforms CD44v3 and CD44v6 is increased on T cells from patients with systemic lupus erythematosus and is correlated with disease activity

José C. Crispín
Objective To quantify the expression of CD44 and variant isoforms CD44v3 and CD44v6 on T cells from patients with systemic lupus erythematosus (SLE), and to assess correlations of the level of expression of these molecules with disease manifestations. Methods Information on clinical and demographic characteristics was collected, and blood samples were obtained from 72 patients with SLE and 32 healthy control subjects matched to the patients by sex, race, and age. Expression of CD44 and variants CD44v3 and v6 on T cell subsets was determined by flow cytometry, and Pearson's correlations of their expression levels with clinical variables, SLE Disease Activity Index (SLEDAI) scores, and presence of lupus nephritis were determined. Wilcoxon's rank sum tests and conditional multivariable regression analyses were applied to identify differences in the expression of CD44 between patients with SLE and healthy controls. Results Expression of CD44 was higher on CD4+ and CD8+ T cells from SLE patients compared with controls (P , 0.03). Expression of CD44v3 and CD44v6 was also higher on total T cells and CD4+ and CD8+ T cells from SLE patients compared with controls (P , 0.03). Cell surface levels of CD44v3 on total T cells, CD4+ T cells, and CD8+ T cells as well as cell surface expression of CD44v6 on total T cells and CD4+ T cells were correlated with the SLEDAI score (P < 0.05). The presence of lupus nephritis was associated with the expression of CD44v6 on total T cells, CD4+ T cells, and CD4,CD8, T cells (P < 0.05). Positivity for anti,double-stranded DNA antibodies was associated with the expression levels of CD44v6 on T cells (P < 0.05). Conclusion These results indicate that expression levels of CD44v3 and CD44v6 on T cells may represent useful biomarkers of SLE activity. [source]

A proof-of-principle gel-free proteomics strategy for the identification of predictive biomarkers for the onset of pre-eclampsia

RT Blankley
Objective, Progress in the prevention and treatment of women at risk of pre-eclampsia (PE) still remains hindered by the lack of clinical screening tools that can accurately predict which mothers are at risk. The identification and validation of predictive biomarkers is therefore seen as a critical milestone towards improved healthcare provision and the clinical testing of new therapeutic strategies. Gel-free proteomic technologies offer the capability of analysing hundreds of plasma proteins simultaneously, but as yet these methods have not been applied to pregnancy complications. To assess the feasibility of such an approach to plasma biomarker research in pregnancy we have applied the technique to samples from women with PE to gestation-matched controls. Sample, Pooled plasma samples taken at time of disease from women with PE (n = 23) and gestation-matched controls (n = 23). Methods, Proteomics strategy for relative quantification of proteins using mass spectrometry. Results, We identified several differences, including elevated levels of endoglin, PAPP-A and PSG1 in PE plasma. Increased levels of endoglin were validated using immunoassay analysis of individual plasma samples. Conclusions, Although at a relatively early stage, this mass spectrometry-based approach shows promise as a tool to identify global protein changes in plasma. The application of these methods to pre-disease samples is the next step in the identification of clinically useful biomarkers. [source]

Extracellular matrix metabolites as potential biomarkers of disease activity in wound fluid: lessons learned from other inflammatory diseases?

R. Moseley
Summary The new era of pharmacogenetics has identified a potential for individuals to receive customized treatments for a variety of disease states. For such individualized treatments to fulfil their potential, it will be essential for clinicians to be able to monitor disease activity, ideally in a rapid, noninvasive fashion. The accessibility of the skin offers much potential to develop noninvasive tests of metabolic and disease activity for clinical use. Impaired human wound healing in the skin is a chronic inflammatory disorder in which the development of such tests has considerable potential, aiding clinical decision making and monitoring responses to treatment. This review article discusses how studies in other human diseases have highlighted potential biochemical markers (biomarkers) of disease activity in secreted biofluids, as aids to determining disease and metabolic activity within tissues. Using, as examples, lessons learned in the study of disease activity and prognosis of other chronic inflammatory conditions, such as osteoarthritis and periodontal disease, this review highlights the potential of dermal extracellular matrix (ECM) components (collagens, proteoglycans, hyaluronan and glycoproteins) for such uses. The limitations of currently utilized techniques and the concept that analysis of ECM components in wound fluid may represent useful biomarkers of disease activity are also discussed. [source]