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Disease Markers (disease + marker)
Selected AbstractsAortic Valve Sclerosis: Is It a Cardiovascular Risk Factor or a Cardiac Disease Marker?ECHOCARDIOGRAPHY, Issue 3 2007F.I.S.C.U., Pasquale Palmiero M.D. Background: Aortic valve sclerosis, without stenosis, has been associated with an increased cardiovascular mortality and morbidity due to myocardial infarction. However, it is unclear whether it is a cardiovascular risk factor or a cardiac disease marker. The goal of our study is to evaluate the difference in the prevalence of cardiovascular disease and risk factors among patients with or without aortic sclerosis. Methods: This observational study compared a group of 142 consecutive subjects with aortic valve sclerosis, assigned as group S, with a group of 101 subjects without aortic sclerosis, assigned as group C. Patients with bicuspid aortic valves and those with antegrade Doppler velocity across aortic valve leaflets exceeding 2.0 m/sec were excluded. Results: Mean ages of groups S and C were 71 ± 8, and 68.8 ± 6 years, respectively (P value = not significant). The prevalence of smoking, diabetes, hypercholesterolemia, hypertension, pulse pressure, left ventricular diastolic dysfunction, atrial fibrillation, and stroke was not significantly different between the two groups. However, there was a significantly higher prevalence of left ventricular hypertrophy (P = 0.05), ventricular arrhythmias (P = 0.02), myocardial infarction (P = 0.04), and systolic heart failure (P = 0.04) in aortic sclerosis group. Conclusions: Aortic sclerosis is associated with a higher prevalence of left ventricular hypertrophy, ventricular arrhythmias, myocardial infarction, and systolic heart failure, while the prevalence of cardiovascular risk factors is not different between aortic sclerosis patients and controls. Hence, aortic sclerosis represents a cardiac disease marker useful for early identification of high-risk patients beyond cardiovascular risk factors rate. [source] Hypermethylation of gene promoters in hematological neoplasiaHEMATOLOGICAL ONCOLOGY, Issue 4 2002C. S. Chim Abstract Cancer cells are associated with global hypomethylation but with focal hypermethylation of specific gene promoters organized as CpG island. DNA methyltransferases, DNMT1 and 3 (3a and 3b), have been implicated in mediating maintenance and de novo methylation. Hypermethylation of gene promoters results in the inactivation of the corresponding genes, by preclusion of the formation of the transcription complex, due to the recruitment of MBP, MeCPs and histone deacetylase. This results in the deacetylation of histone and thus a compact chromatin complex unfavourable for the initiation of transcription. This methylation-associated gene silencing has been demonstrated in various genes including tumour suppressor genes (p15, p16, p73, VHL). Therefore, gene promoter hypermethylation collaborates with other mechanisms of gene inactivation such as deletion and intragenic mutations to fulfil Knudson's hypothesis. Hypermethylation may serve as a molecular disease marker for the detection of minimal residual disease. Emerging evidence suggests a possible prognostic value of gene promoter hypermethylation. Moreover, gene hypermethylation may also serve as a target for therapeutic invention by hypomethylating agents. Copyright © 2002 John Wiley & Sons, Ltd. [source] Fecal S100A12 and fecal calprotectin as noninvasive markers for inflammatory bowel disease in childrenINFLAMMATORY BOWEL DISEASES, Issue 3 2008Marc A. Sidler MD Abstract Background: Fecal calprotectin is a sensitive marker for gut inflammation. Recently, we have established that a related protein, S100A12, is elevated in the feces of children with inflammatory bowel disease (IBD). This may represent a specific and sensitive disease marker. The objective was to investigate the utility of fecal S100A12, in comparison to fecal calprotectin and standard inflammatory markers, as a screening marker for IBD in children with gastrointestinal symptoms. Methods: Stool samples were obtained from 61 children presenting with gastrointestinal symptoms requiring endoscopy. Fecal S100A12, calprotectin, and serum S100A12 levels were measured and correlated to final diagnosis and standard tests (ESR, CRP, platelet count, and albumin). Results: Children diagnosed with IBD (n = 31) had elevated fecal S100A12 (median 55.2 mg/kg) and calprotectin (median 1265 mg/kg) levels compared with the children without IBD (n = 30; S100A12: median 1.1 mg/kg, P < 0.0001; calprotectin: median 30.5 mg/kg; P < 0.0001). The sensitivity and specificity of fecal S100A12 (cutoff 10 mg/kg) for the detection of IBD were both 97%, whereas fecal calprotectin (cutoff 50 mg/kg) gave a sensitivity of 100% and a specificity of 67%. Conclusions: Both fecal markers were superior to the sensitivities and specificities of any standard inflammatory test. Both fecal S100A12 and calprotectin are sensitive markers of gastrointestinal inflammation, but fecal S100A12 provided exceptional specificity in distinguishing children with IBD from children without IBD. Fecal S100A12 is a simple, noninvasive test that can be used to screen and select children warranting further invasive and laborious procedures such as endoscopy for the investigation of their gastrointestinal symptoms. (Inflamm Bowel Dis 2007) [source] Reduced N -acetylaspartate is consistent with axonal dysfunction in cerebral small vessel diseaseNMR IN BIOMEDICINE, Issue 3 2009Arani Nitkunan Abstract Background: Cerebral small vessel disease (SVD) is an important cause of cognitive impairment, but the pathophysiological mechanisms remain unclear. We used 1H MRS to investigate brain metabolic differences between patients with SVD and controls and correlated this with cognition. Methods: 35 patients with SVD (lacunar stroke and radiological evidence of confluent leukoaraiosis) and 35 controls underwent multi-voxel spectroscopic imaging of white matter to obtain absolute metabolite concentrations of N -acetylaspartate (NAA), total creatines, total cholines, myo -inositol, and lactate. A range of cognitive tests was performed on patients with SVD, and composite scores were calculated. Results: Scans of sufficient quality for data analysis were available in 29 cases and 35 controls. NAA was significantly reduced in patients compared with controls (lower by 7.27%, P,=,0.004). However, when lesion load within each individual voxel (mean 22% in SVD vs 5% in controls, P,<,0.001) was added as a covariate, these differences were no longer significant, suggesting that the metabolite differences arose primarily from differences in lesioned tissue. In patients with SVD, there was no correlation between cognitive scores and any brain metabolite. No lactate, an indicator of anaerobic metabolism, was detected. Conclusions: The most consistent change in SVD is a reduction in NAA, a marker of neuronal integrity. The lack of correlation with cognition does not support the use of MRS as a surrogate disease marker. Copyright © 2008 John Wiley & Sons, Ltd. [source] Prenatal diagnosis in a family with X-linked hydrocephalusPRENATAL DIAGNOSIS, Issue 10 2005Maria Panayi Abstract The neural cell adhesion molecule L1 is a transmembrane glycoprotein belonging to the immunoglobulin superfamily of cell adhesion molecules (CAMs). Its expression is essential during embryonic development of the nervous system and it is involved in cognitive function and memory. Mutations in the L1CAM gene are responsible for four related L1 disorders; X-linked hydrocephalus/HSAS (Hydrocephalus as a result of Stenosis of the Aqueduct of Sylvius), MASA (Mental retardation, Aphasia, Shuffling gait, and Adducted thumbs) syndrome, X-linked complicated spastic paraplegia type I (SPG1) and X-linked Agenesis of the Corpus Callosum (ACC). These four disorders represent a clinical spectrum that varies both between and within families. The main clinical features of this spectrum are Corpus callosum hypoplasia, mental Retardation, Adducted thumbs, Spastic paraplegia and Hydrocephalus (CRASH syndrome). Since there is no biochemically assayed disease marker, molecular analysis of the L1CAM gene is the only means of confirming a clinical diagnosis. Most L1CAM mutations reported to date are point mutations (missense, nonsense, splice site) and only a few patients with larger rearrangements have been documented. We have characterised a rare intragenic deletion of the L1CAM gene in a sample of DNA extracted from a chorionic villus biopsy (CVB) performed at 12 weeks' gestation. Copyright © 2005 John Wiley & Sons, Ltd. [source] Phenotyping of epidermal dendritic cells allows the differentiation between extrinsic and intrinsic forms of atopic dermatitisBRITISH JOURNAL OF DERMATOLOGY, Issue 6 2000T. Oppel Atopic dermatitis (AD) is a clinically characteristic, chronic inflammatory skin disease of unknown origin. IgE-mediated uptake and antigen focusing of environmental allergens by dendritic cells (DCs) is assumed to be a central immunopathogenetic event. A so-called intrinsic type of AD (IAD) has been delineated from the more common extrinsic AD (EAD) by normal serum IgE levels, negative RAST tests and negative immediate-type skin reactions towards environmental allergens. The recently characterized human autoantigen Hom S 1 has been proposed to play a part in the pathogenesis of IAD. Objectives,To compare clinical and laboratory data between patients with IAD and EAD, and to investigate potential differences in the inflammatory micromilieu of the epidermal compartment in IAD and EAD lesions. Methods,Epidermal DC phenotyping, a recently validated technique based on the three-colour flow cytometric analysis of Langerhans cells and the so-called inflammatory dendritic epidermal cells from epidermal single-cell suspensions, was performed on samples from 69 patients with AD (seven with IAD and 62 with EAD) and 94 controls. Results,Patients with EAD tended to have an earlier onset of disease but similar disease duration and family history of atopic diseases. Quantitative analysis of CD36 expression on DCs as a marker of inflammation, as well as the percentage of inflammatory dendritic epidermal cells in the CD1a+ epidermal DC pool, indicated a comparable disease activity in IAD and EAD. EAD was characterized by a significantly higher Fc,RI expression on the CD1a+ epidermal DCs than IAD. Using the Fc,RI/Fc,RII expression ratio as a disease marker for AD, values for IAD fell below the diagnostic cut-off level of 1·5 for this ratio. Conclusions,While IAD is clinically similar to EAD, the inflammatory microenvironment in this condition seems different from classical EAD and can be distinguished by phenotyping of epidermal DCs. [source] Refining exposure definitions for studies of periodontal disease and systemic disease associationsCOMMUNITY DENTISTRY AND ORAL EPIDEMIOLOGY, Issue 6 2008Ryan T. Demmer Abstract,,, Background:, Substantial variation exists in reported associations between periodontal infections and cardiovascular disease. Imprecise periodontal exposure definitions are possible contributors to this variability. We studied appropriate exposure definitions for studying associations between clinical periodontal disease (PD) and systemic disease. Methods:, Data originate from men and women aged 20,79 enrolled in the Study of Health in Pomerania (SHIP) from 1997,2001. Age and sex-adjusted correlation analysis identified PD definitions with the highest cross-sectional associations with three subclinical markers of systemic disease: plasma fibrinogen (n = 3481), serum hemoglobin A1c (HbA1c) (n = 3480), and common carotid artery intima-media thickness (c-IMT) (n = 1745, age , 45). Results:, In men and women, percent of sites with attachment loss (AL) ,6 mm and tooth loss both revealed the highest correlation with HbA1c (, = 0.11; several other definitions related similarly), while the strongest fibrinogen correlation was observed with percent of sites with pocket depth ,3 mm (, = 0.19). Findings for c-IMT among men were strongest for percent of sites with AL ,6 mm (, = 0.14; several other definitions related similarly) while among women, percent of sites with pocket depth ,5 or 6 mm had the highest observed correlation (, = 0.13). Conclusions:, A range of near optimal definitions varied according to gender and whether the systemic disease marker reflected an acute or chronic situation. Pocket depth was more strongly correlated with the acute marker fibrinogen while attachment and tooth loss tended to be more strongly correlated with the chronic markers, HbA1c, and c-IMT. These findings can be useful in designing future studies investigating the association between PD and systemic disease. [source] The role of electrophoresis in disease biomarker discoveryELECTROPHORESIS, Issue 12 2007Haleem J. Issaq Dr. Abstract There has been increased activity in the last few years in the search for disease markers using fractionation of complex biological fluids combined with MS. While electrophoretic and chromatographic separations have played a major role in this endeavor, this manuscript is limited to a review of electrophoretic methods that have been established for disease biomarker discovery. These methods include 2-DE, difference gel electrophoresis (DIGE), and CE. We define what constitutes a biomarker, identify the steps required for establishing a biomarker, and describe the parameters needed in the design of an ideal diagnostic test. The application, advantages, and limitations of CE, DIGE, and 2-DE in meeting the goal of discovering novel biomarkers is discussed in detail, along with a few selected examples that illustrate the search for biomarkers for cancer and neurological diseases. [source] Quantitative assessment of WT1 gene expression after allogeneic stem cell transplantation is a useful tool for monitoring minimal residual disease in acute myeloid leukemiaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2009Anna Candoni Abstract Introduction:,WT1 overexpression is described in several oncological diseases including acute myeloid leukemia (AML). Quantification of WT1 in bone marrow samples may be useful as a marker of minimal residual disease (MRD) and may predict the relapse of AML after allogeneic hematopoietic stem cell transplant (HSCT). Methods and results:, The quantitative expression of WT1 was measured in 38 AML patients (16 males and 22 females) at diagnosis, at the time of transplant and after the allogeneic HSCT (at precise time points). All cases showed high WT1 expression levels at diagnosis with a mean of 4189 (SD 3325) and a median of 3495 (range 454,13923) copies WT1/104Abl. At transplant, 25 patients (66%) were in complete cytologic remission (CcR) and 13 (34%) had refractory or relapsed AML. Bone marrow samples from patients transplanted in CcR showed significantly lower WT1 expression levels during HSCT compared with the samples from patients with a relapsed or refractory AML (P = 0.004). After HSCT, a rapid decline in WT1 expression levels was observed in all patients who attained or maintained a condition of CcR. Six of 38 patients (13%) relapsed after HSCT and all of them had an increase in WT1 expression at/or before relapse. Five of these six patients died of leukemia and one was successfully reinduced with donor lymphocyte infusion (DLI) + chemotherapy with a rapid reduction of WT1 levels. Besides, we found a complete concordance between WT1 expression levels and other disease markers (when available). Conclusions:, In our experience, there was a complete concordance between WT1 expression levels (measured by quantitative RT-PCR at precise time points) and status of AML before and after allogeneic HSCT. WT1 may be useful as a non-specific leukemia marker for monitoring MRD and as a predictor of AML clinical relapse. Based on these results, cases with increase of WT1 levels after HSCT and without graft vs. host disease may be candidate to discontinuation of immunosuppression and/or DLI therapy. [source] A Three-Dimensional and Sensitive Bioassay Based on Nanostructured Quartz Combined with Viral NanoparticlesADVANCED FUNCTIONAL MATERIALS, Issue 12 2010Jong-Hwan Lee Abstract An effective mask-free method for fabricating high-aspect-ratio pillarlike nanostructures over a large area of a quartz surface via a simple O2 and CF4 two-step reactive ion etching (RIE) procedure is developed. The nanostructured quartz surfaces are successfully combined with the engineered viral particles derived from hepatitis B virus capsid, yielding a novel 3D assay system with attomolar sensitivity, which has great potential for use in sensitive and early detection of various disease markers. [source] Gene-expression signature of adhesion/growth-regulatory tissue lectins (galectins) in transitional cell cancer and its prognostic relevanceHISTOPATHOLOGY, Issue 5 2007S Langbein Aims:, Lectins, and especially galectins, appear to be important in malignancy-associated processes. The aim was to analyse comprehensively the presence of galectins in urothelial tumours. Methods and results:, Non-cross-reactive antibodies against seven family members from the three subgroups (prototype: galectin-1, -2 and -7; chimera type: galectin-3; tandem-repeat type: galectin-4, -8 and -9) were used. Gene expression was monitored in specimens of normal urothelium, fresh tumour tissue and cell lines by real-time polymerase chain reaction (PCR). The presence and evidence of tumour-associated up-regulation were shown for galectin-1 and -3. This was less clear-cut for galectin-4 and -8. Galectin-7 was expressed in all cell lines; galectin-2 and -9 were detected at comparatively low levels. Galectin-2, -3 and -8 up-regulation was observed in superficial tumours, but not in muscle-invasive tumours (P < 0.05). Immunoreactivity correlated with tumour grading for galectin-1, -2 and -8, and disease-dependent mortality correlated with galectin-2 and -8 expression. Binding sites were visualized using labelled galectins. Conclusions:, The results demonstrate a complex expression pattern of the galectin network in urothelial carcinomas. Galectin-1, -2, -3 and -8 are both potential disease markers and also possible targets for bladder cancer therapy. [source] Classification of cancer types by measuring variants of host response proteins using SELDI serum assaysINTERNATIONAL JOURNAL OF CANCER, Issue 5 2005Eric T. Fung Abstract Protein expression profiling has been increasingly used to discover and characterize biomarkers that can be used for diagnostic, prognostic or therapeutic purposes. Most proteomic studies published to date have identified relatively abundant host response proteins as candidate biomarkers, which are often dismissed because of an apparent lack of specificity. We demonstrate that 2 host response proteins previously identified as candidate markers for early stage ovarian cancer, transthyretin and inter-alpha trypsin inhibitor heavy chain 4 (ITIH4), are posttranslationally modified. These modifications include proteolytic truncation, cysteinylation and glutathionylation. Assays using Surface Enhanced Laser Desorption/Ionization Time of Flight Mass Spectrometry (SELDI-TOF-MS) may provide a means to confer specificity to these proteins because of their ability to detect and quantitate multiple posttranslationally modified forms of these proteins in a single assay. Quantitative measurements of these modifications using chromatographic and antibody-based ProteinChip® array assays reveal that these posttranslational modifications occur to different extents in different cancers and that multivariate analysis permits the derivation of algorithms to improve the classification of these cancers. We have termed this process host response protein amplification cascade (HRPAC), since the process of synthesis, posttranslational modification and metabolism of host response proteins amplifies the signal of potentially low-abundant biologically active disease markers such as enzymes. © 2005 Wiley-Liss, Inc. [source] Risk-Based Classification of Hypertension and the Role of Combination TherapyJOURNAL OF CLINICAL HYPERTENSION, Issue 2008Matthew R. Weir MD The recognition of a continuous relationship between elevated blood pressure (BP) and cardiovascular risk has influenced national and international guidelines for the classification, prevention, and management of hypertension. The most recent report (2003) of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure uses BP thresholds to define categories of normal, prehypertension, and hypertension. A new definition proposed by the Hypertension Writing Group in 2005 offers an approach to diagnosis and management based on global or total risk. Thus, even in the absence of sustained elevations in BP, patients may have a moderate to high risk of vascular events due to the presence of additional cardiovascular risk factors, disease markers, and target organ damage. The 2007 European guidelines continue to classify hypertension based on cutoffs while also placing emphasis on multivariate formulations for cardiovascular risk assessment and goals of therapy. All 3 sets of guidelines acknowledge the necessity of using ,2 antihypertensive agents to attain BP goals in many patients. [source] Risk factors for periodontal disease progression among elderly peopleJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 7 2002Hiroshi Ogawa Abstract The aim of this study was to identify the risk factors for periodontal disease progression by individual characteristics at baseline among elderly people over a 2-year period. Subjects were selected from 4542 people aged 70 years residing in Niigata who were in good general health and who did not require special care for their daily activities. Gender, smoking and alcohol drinking habits were obtained using a questionnaire, while serum levels of disease markers were investigated and attachment levels were clinically recorded. For the assessment of periodontal disease progression, additional attachment loss was used if one or more sites had a 3-mm or more increase in probing attachment level over a 2-year period. In all, 394 subjects (208 males and 186 females) were surveyed. Approximately 75% of subjects exhibited additional attachment loss over a 2-year period. Significant associations were found between additional attachment loss and smoking, and attachment level of 6 mm or more at baseline, with odds ratios of 3.75 and 2.29, respectively. Smoking habit and baseline attachment level of 6 mm or more may be considered risk factors for further attachment loss among healthy elderly people. [source] Seroprevalence, risk factors, and hepatitis C virus genotypes in groups with high-risk sexual behavior in CroatiaJOURNAL OF MEDICAL VIROLOGY, Issue 8 2009Tatjana Vilibic Cavlek Abstract The seroprevalence, risk factors and genotypes of hepatitis C virus (HCV) in groups with high-risk sexual behavior (persons with multiple sexual partners, men who have sex with men, commercial sex workers and their clients and persons with sexually transmitted diseases) in seven Croatian cities were analyzed. A total of 821 participants without history of injecting drug use were included in the study. Anti-HCV prevalence among risk groups varied from 2.9% to 8.5% with an overall prevalence of 4.6% (95% CI,=,3.2,6.1) compared with 0.5% (95% CI,=,0.0,1.5) in controls (pregnant females; OR,=,9.66; 95% CI,=,1.32,70.7). HCV-RNA was detected in 73.1% anti-HCV positive patients. Three of the seronegative cases (2.1%) were also found to be HCV-RNA positive ("window period"). Genotype 1 was most commonly detected (55.6%). The most prevalent subtypes were 1a (38.9%) and 3a (38.9%). Sociodemographic characteristics (age, gender, marital status and level of education) were not associated with anti-HCV seropositivity. Among sexually transmitted disease markers, a higher seroprevalence of HCV infection was found in subjects with a history of HBV infection (10.5% vs. 3.8%, P,=,0.002) and gonorrhea (13.2% vs. 4.2%, P,=,0.011). No other factors reflecting risk sexual behavior such as sexual orientation, number of sexual partners and number of risk behaviors were associated with HCV seroprevalence. J. Med. Virol. 81:1348,1353, 2009. © 2009 Wiley-Liss, Inc. [source] Selection of bead-displayed, PNA-encoded chemicalsJOURNAL OF MOLECULAR RECOGNITION, Issue 5 2010Natalie R. Gassman Abstract The lack of efficient identification and isolation methods for specific molecular binders has fundamentally limited drug discovery. Here, we have developed a method to select peptide nucleic acid (PNA) encoded molecules with specific functional properties from combinatorially generated libraries. This method consists of three essential stages: (1) creation of a Lab-on-BeadÔ library, a one-bead, one-sequence library that, in turn, displays a library of candidate molecules, (2) fluorescence microscopy-aided identification of single target-bound beads and the extraction , wet or dry , of these beads and their attached candidate molecules by a micropipette manipulator, and (3) identification of the target-binding candidate molecules via amplification and sequencing. This novel integration of techniques harnesses the sensitivity of DNA detection methods and the multiplexed and miniaturized nature of molecule screening to efficiently select and identify target-binding molecules from large nucleic acid encoded chemical libraries. Beyond its potential to accelerate assays currently used for the discovery of new drug candidates, its simple bead-based design allows for easy screening over a variety of prepared surfaces that can extend this technique's application to the discovery of diagnostic reagents and disease markers. Copyright © 2009 John Wiley & Sons, Ltd. [source] Duodenal mastocytosis, eosinophilia and intraepithelial lymphocytosis as possible disease markers in the irritable bowel syndrome and functional dyspepsiaALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2009M. M. WALKER Summary Background, Irritable bowel syndrome (IBS) and functional dyspepsia (FD) are common functional disorders without defined pathology. Mast cells and eosinophils interact with T lymphocytes and may alter enteric nerve and smooth muscle function. Aim, To examine mast cell, eosinophil and intraepithelial lymphocyte populations in duodenal biopsies of subjects with IBS and FD. Methods, A random sample of an adult Swedish population (n = 1001; mean age 54 years; 51% female) underwent upper endoscopy and biopsy; 51 cases with FD and 41 cases with IBS were compared with 48 randomly selected controls. Eosinophils were identified by light microscopy; mast cells by immunocytochemistry (CD117). Intraepithelial lymphocytes were counted per 100 enterocytes. Cell counts were quantified by counting the number per high power field (HPF) in 5HPFs in the bulb (D1) and second part of duodenum (D2), summed over 5HPFs at each site. Results, Cases and controls showed similar demographics. Compared to controls, IELs in IBS-constipation were significantly increased (P = 0.005). Mast cells were significantly increased in IBS in D2 (P < 0.001), while eosinophils were significantly increased in FD in D1 and D2 (P < 0.001). Conclusion, Duodenal mast cell hyperplasia is linked to IBS and eosinophilia to FD, and duodenal biopsy may identify subsets of these disorders. [source] Outcome of active disease in ankylosing spondylitis: A prospective studyMUSCULOSKELETAL CARE, Issue 1 2010Grad Dip Phys, J. Martindale PhD Abstract Background:,People with ankylosing spondylitis (AS) typically experience episodic exacerbations, but the extent to which they subsequently experience a sustained reduction in disease markers below recognized thresholds for active disease is unclear. Objective:,To investigate changes in, and associations between, disease markers over 18 months in people with active AS. Methods:,Within a cohort of 89 participants with AS, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores of 4 or higher were used to identify those with active disease. Standard assessment tools were used to monitor participants prospectively at four consecutive six-monthly intervals. Participants received standard treatments but none received anti-tumor necrosis factor-alpha (TNF,) medication during the study. Results:,The median age of the cohort was 50 years (inter-quartile range [IQR] 38.5,55.5), the median age of disease onset was 25 years (IQR 18,33) and the median disease duration was 18 years (IQR 13,27). Forty-seven (53%) participants had a BASDAI score of 4 or higher on the first assessment, of whom 45 (51%) scored 4 or higher on all subsequent assessments. Furthermore, 38 (43%) and 16 (18%) participants scored BASDAI 5 or 6, respectively, or higher, throughout. BASDAI scores correlated strongly with Bath Ankylosing Spondylitis Functional Index (BASFI) scores. Compared with 19 (21%) participants whose BASDAI scores were consistently below 4 throughout, participants with persistently high BASDAI scores showed higher scores for anxiety and depression, and some evidence of functional deterioration during the study period. Conclusions:,In this cohort, disease markers in most people with active AS were sustained above the standard threshold for active disease. This has important implications for planning care pathways and for optimal utilization of anti-TNF, treatment. Copyright © 2009 John Wiley & Sons, Ltd. [source] Perspectives for imaging mass spectrometry in the proteomics landscapePROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 4 2009Luke MacAleese Abstract A number of techniques are used in the field of proteomics that can be combined to get the most molecular information from a specific biological sample, fluid or tissue. Imaging techniques are often used to obtain local information from tissue samples. However, imaging experiments are often staining experiments, which rely on specific or aspecific interactions between fluorescent markers and pre-defined (families of) peptide or protein. Therefore, imaging is often used as a screening or validation tool for the local presence of proteins that have been identified by other means. Imaging mass spectrometry (IMS) combines the advantages of MS and microscopy in a single experiment. It is a technique that does not require any labeling of the analytes and provides a high multiplexing capability combined with the potential for analyte identification. It enables simultaneous detection of potentially all peptides and proteins present at a tissue surface and is used for the determination and identification of tissue-specific disease markers. The workflows of IMS experiments closely resemble those of conventional proteomics. In this review, we describe IMS experiments step-by-step to position and evaluate the role of IMS in a comparative proteomics landscape. We illustrate in a concise review that IMS is a true discovery oriented tool for proteomics that seamlessly integrates in conventional proteomics workflows and can be perceived as either an alternative or complementary proteomics technique. [source] Cancer biomarker discovery via low molecular weight serum proteome profiling , Where is the tumor?PROTEOMICS - CLINICAL APPLICATIONS, Issue 12 2007Michael T. Davis Abstract Time-course analyses of rapidly processed serum performed in parallel by SELDI and nanoscale LC-MS/MS have revealed the temporal correlation of several literature-based disease markers with ex vivo driven events such that their in vivo existence in healthy subjects is questionable. Identification by MS/MS reveals these putative biomarkers to be byproducts of the coagulation cascade and platelet activation and suggests plasmatic analysis may be preferred. In a pilot plasmatic study, a cohort of naïve prostate cancer (PCa) samples were uniformly distinguished from their age-matched controls (n,=,20) on the basis of multiple peptidic components; most notably by a derivative of complement C4 at 1863,m/z (GLEEELQFSLGSKINVK, C41353,1369). The fully tryptic nature of this and other putative PCa discriminants is consistent with the cleavage specificity of common blood proteases and questions the need for tumor-derived proteolytic activities as has been proposed. In light of the known correlation of disregulated hemostasis with malignant disease, we suggest the underlying differentiating phenomena in these types of analyses may lie in the temporal disparity of sample activation such that the case (patient) samples are preactivated while the control samples are not. [source] High-throughput single molecule screening of DNA and proteinsTHE CHEMICAL RECORD, Issue 2 2001Edward S. Yeung Abstract We report a novel imaging technology for real time comprehensive analysis of molecular alterations in cells and tissues appropriate for automation and adaptation to high-throughput applications. With these techniques it should eventually be possible to perform simultaneous analysis of the entire contents of individual biological cells with a sensitivity and selectivity sufficient to determine the presence or absence of a single copy of a targeted analyte (e.g., DNA region, RNA region, protein), and to do so at a relatively low cost. The technology is suitable for DNA and RNA through sizing or through fluorescent hybridization probes, and for proteins and small molecules through fluorescence immunoassays. This combination of the lowest possible detection limit and the broadest applicability to biomolecules represents the final frontier in bioanalysis. The general scheme is based on novel concepts for single molecule detection (SMD) and characterization recently demonstrated in our laboratory. Since minimal manipulation is involved, it should be possible to screen large numbers of cells in a short time to facilitate practical applications. This opens up the possibility of finding single copies of DNA or proteins within single biological cells for disease markers without performing polymerase chain reaction or other biological amplification. © 2001 John Wiley & Sons, Inc. and The Japan Chemical Journal Forum Chem Rec 1:123,139, 2001 [source] Effect of the urotensin-II receptor antagonist palosuran on secretion of and sensitivity to insulin in patients with Type 2 diabetes mellitusBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 4 2009Patricia N. Sidharta WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Urotensin-II (U-II) is one of the most potent vasoconstrictors identified thus far. , Although differences in both U-II blood levels and U-II receptor (UT-receptor) expression have been observed in patients with cardiovascular and cardiorenal disease, the precise function in humans has not been elucidated. , U-II and its receptor have been reported to be involved in glucose metabolism and insulin resistance, which can lead to the development of Type 2 diabetes mellitus. , In rat models of diabetes, palosuran, a selective, potent antagonist of the human UT-receptor, improved several disease markers. WHAT THIS STUDY ADDS , In this study in diabetic patients, the effects of palosuran on insulin secretion and sensitivity were investigated using a hyperglycaemic glucose clamp and a meal tolerance test and daily glucose levels were also studied. , Although no obvious beneficial effect of palosuran in this patient population was observed, the study contributes to providing more insight inro the human U-II/UT-receptor system. AIMS To investigate the effects of palosuran, a nonpeptidic, potent and selective antagonist of the urotensin-II receptor, on insulin and glucose regulation in 20 diet-treated patients with Type 2 diabetes mellitus in a double-blind, placebo-controlled, randomized, crossover, proof-of-concept study. METHODS After 4 weeks' oral treatment with 125 mg palosuran or placebo b.i.d., effects on insulin secretion and sensitivity and blood glucose levels were assessed by means of a hyperglycaemic glucose clamp, meal tolerance test, homeostasis model assessment-insulin resistance score, and daily self-monitoring of blood glucose. Plasma concentrations of palosuran were determined for 12 h on the last day of intake. RESULTS Palosuran did not affect second-phase insulin response (primary end-point) during the hyperglycaemic glucose clamp in comparison with placebo [paired difference of ,1.8 µU ml,1, 95% confidence interval (CI) ,7.8, 4.2]. Likewise, no effects of palosuran were detected on the first-phase insulin response, or on insulin secretion and blood glucose levels during the meal tolerance test or on homeostasis model assessment-insulin resistance score. No clinically significant effects on daily blood glucose profiles were observed during the study. Geometric mean Cmax and AUC, (95% CI) and median tmax (range) in this patient population were 180 ng ml,1 (125, 260), 581 ng·h ml,1 (422, 800) and 3.0 h (0.67, 4.3), respectively. CONCLUSIONS The results of this study indicate that antagonism of the urotensin-II system does not influence insulin secretion or sensitivity or daily blood glucose levels in diet-treated patients with Type 2 diabetes. [source] Presentation of new GINA guidelines for paediatricsCLINICAL & EXPERIMENTAL ALLERGY, Issue 2000Von Mutius The Global Initiative on Asthma (GINA) has provided guidelines for the management of children with asthma. For a step-wise approach to therapy, asthma is divided into four categories based on severity of symptoms: intermittent, mild persistent, moderate persistent, and severe persistent asthma. Long-term preventive therapy is distinguished from quick relief therapy in each group. Although these guidelines are clear and simple there have been few studies on asthma therapy for infants. Moreover, the existence of different wheezing phenotypes with varying pathogenic mechanisms hampers the interpretation of these studies. Transient wheezers have stopped wheezing by the age of 3 years and there is no relationship to atopy or a family history of asthma. In contrast, persistent wheezers continue to wheeze from the first year of life throughout school-age and have a high risk of atopy. Although they have normal lung function at birth, persistent wheezers develop significant decrements in lung function by the age of 6 years. Whether these impairments are amenable to prevention by early initiation of anti-inflammatory therapy remains to be seen. At present, there are no disease markers to identify the different wheezing phenotypes in infancy, although eosinophil counts and measurements of eosinophil cationic protein in serum may prove to be helpful in distinguishing these conditions. [source] MicroRNAs: novel regulators in skin inflammationCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 3 2008E. Sonkoly Summary Compelling evidence indicates that microRNAs (miRNAs), short, non-protein coding RNAs, are critical for the development and survival of multicellular organisms. Recently, miRNAs were implicated in the pathogenesis of psoriasis and atopic eczema (AE), the two most common chronic inflammatory disorders in skin. In particular, miR-203, the first skin-specific miRNA, showing an intriguing expression profile being confined to skin epithelium, is specifically overexpressed in psoriasis. MiR-146a, another miRNA showing specific upregulation in psoriasis, is involved in the regulation of innate immune responses and the tumour necrosis factor (TNF)-, pathway. Interestingly, miR-125b, another miRNA involved in the TNF-, pathway, is also deregulated in psoriasis and AE. As skin inflammation may serve as a model for chronic inflammatory disorders, it is likely that miRNAs involved in skin inflammation will eventually emerge in other inflammatory or autoimmune disorders, and some of these may become disease markers and therapeutic targets. In this review we present an overview of what is currently known about the roles of miRNAs in chronic inflammatory skin disorders. [source] | |||||||||||||||||||||||||||||||