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Highly Specific (highly + specific)

Distribution by Scientific Domains
Medical Sciences42%
Life Sciences35%
Chemistry21%

Terms modified by Highly Specific

  • highly specific marker
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    Selected Abstracts

    A prospective study of the diagnostic accuracy of cytological criteria in the FNAB diagnosis of breast papillomas

    DIAGNOSTIC CYTOPATHOLOGY, Issue 8 2007
    Andrew Field M.B., F.R.C.P.A.
    Abstract Seventy-four fine needle aspiration biopsies (FNAB) of breast were selected from the 133 cases with surgical biopsy follow up, from a total of 1,154 consecutive breast FNAB received in a 6-month-period. These 74 cases were reviewed and scored using all relevant cytological criteria for proliferative breast lesions used in our recent retrospective study, without reference to the original cytological and surgical biopsy diagnoses. Of the 42 criteria scored, 13 had a statistically significant association between the cytology score and the presence or absence of a papilloma (PAP), and the sensitivities, specificities and positive predictive values (PPV) of these individual criteria, or a combination of criteria, were derived. It was found that stellate and meshwork tissue fragments and papillary fragments were all highly specific (0.98) for the diagnosis of PAP, with meshwork fragments having the highest PPV (0.93). Stellate fragments (0.41) and papillary fragments (0.24) were less sensitive not only because they occurred less often, but also because they were present in smaller numbers. The presence of a proteinaceous background with macrophages and siderophages or a moderate to marked number of apocrine sheets were useful indicators only when coexisting with at least one of the above three features. Diagn. Cytopathol. 2007;35:465,475. © 2007 Wiley-Liss, Inc. [source]

    Monoclonal antibody proteomics: Discovery and prevalidation of chronic obstructive pulmonary disease biomarkers in a single step

    ELECTROPHORESIS, Issue 23 2007
    Eszter Csanky
    Abstract We define mAb proteomics as the global generation of disease specific antibodies that permit mass screening of biomarkers. An integrated, high-throughput, disease-specific mAb-based biomarker discovery platform has been developed. The approach readily provided new biomarker leads with the focus on large-scale discovery and production of mAb-based, disease-specific clinical assay candidates. The outcome of the biomarker discovery process was a highly specific and sensitive assay, applicable for testing of clinical validation paradigms, like response to treatment or correlation with other clinical parameters. In contrast to MS-based or systems biology-based strategies, our process produced prevalidated clinical assays as the outcome of the discovery process. By re-engineering the biomarker discovery paradigm, the encouraging results presented in this paper clearly demonstrate the efficiency of the mAb proteomics approach, and set the grounds for the next steps of studies, namely, the hunt for candidate biomarkers that respond to drug treatment. [source]

    Development of recombinant inhibitors specific to human kallikrein 2 using phage-display selected substrates

    FEBS JOURNAL, Issue 3 2004
    Sylvain M. Cloutier
    The reactive site loop of serpins undoubtedly defines in part their ability to inhibit a particular enzyme. Exchanges in the reactive loop of serpins might reassign the targets and modify the serpin,protease interaction kinetics. Based on this concept, we have developed a procedure to change the specificity of known serpins. First, reactive loops are very good substrates for the target enzymes. Therefore, we have used the phage-display technology to select from a pentapeptide phage library the best substrates for the human prostate kallikrein hK2 [Cloutier, S.M., Chagas, J.R., Mach, J.P., Gygi, C.M., Leisinger, H.J. & Deperthes, D. (2002) Eur. J. Biochem. 269, 2747,2754]. Selected substrates were then transplanted into the reactive site loop of ,1-antichymotrypsin to generate new variants of this serpin, able to inhibit the serine protease. Thus, we have developed some highly specific ,1-antichymotrypsin variants toward human kallikrein 2 which also show high reactivity. These inhibitors might be useful to help elucidate the importance of hK2 in prostate cancer progression. [source]

    Behavioural and physiological characterization of inbred mouse strains: prospects for elucidating the molecular mechanisms of mammalian learning and memory

    GENES, BRAIN AND BEHAVIOR, Issue 2 2002
    P. V. Nguyen
    With the advent of recombinant DNA methodology, it has become possible to dissect the molecular mechanisms of complex traits, including brain function and behaviour. The increasing amount of available information on the genomes of mammalian organisms, including our own, has facilitated this research. The present review focuses on a somewhat neglected area of genetics, one that involves the study of inbred mouse strains. It is argued that the use of inbred mice is complementary to transgenic approaches in the analysis of molecular mechanisms of complex traits. Whereas transgenic technology allows one to manipulate a single gene and investigate the in vivo effects of highly specific, artificially induced mutations, the study of inbred mouse strains should shed light on the roles of naturally occurring allelic variants in brain function and behaviour. Systematic characterization of the behavioural, electrophysiological, neurochemical, and neuroanatomical properties of a large number of inbred strains is required to elucidate mechanisms of mammalian brain function and behaviour. In essence, a ,mouse phenome' project is needed, entailing the construction of databases to investigate possible causal relationships amongst the phenotypical characteristics. This review focuses on electrophysiological and behavioural characterization of mouse strains. Nevertheless, it is emphasized that the full potential of the analysis of inbred mouse strains may be attained if techniques of numerous disciplines, including gene expression profiling, biochemical analysis, and quantitative trait loci (QTL) mapping, to name but a few, are also included. [source]

    Evaluation of an automated screening assay for von Willebrand Disease Type 2N

    INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 6 2002
    S. L. Taylor
    Summary Evaluating the factor VIII (FVIII) binding activity of von Willebrand factor (VWF) is an important step in the diagnostic work-up of families affected by apparent mild haemophilia A. In von Willebrand's disease (VWD) type 2N (Normandy), mutations at the N-terminal end of the mature VWF subunit gene prevent the binding of FVIII. Individuals heterozygous for type 2N VWD are generally asymptomatic. Homozygotes and compound heterozygotes present with a clinical picture which mimics haemophilia A, with a markedly reduced FVIII : C activity and VWF within the normal range, but instead of exhibiting X-linked inheritance they show an autosomal recessive inheritance pattern. The distinction between haemophilia A and VWD type 2N has important implications for therapy and genetic counselling. We present a highly specific enzyme-linked immunosorbent assay screening method for the Normandy variant, which measures VWF : FVIII binding activity in parallel with VWF antigen, using monoclonal capture and detection antibodies. The assay is fully automated using a robotic microtitre plate processor, requiring minimal user intervention and providing the capacity to screen large numbers of patients. [source]

    Quantification of urinary N -acetyl- S - (propionamide)cysteine using an on-line clean-up system coupled with liquid chromatography/tandem mass spectrometry

    JOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 4 2005
    Chien-Ming Li
    Abstract Acrylamide has been reported to be present in high-temperature processed foods and normal processed food intake could lead to significant acrylamide exposure. Acrylamide in vivo can be conjugated with glutathione in the presence of glutathione transferase. This conjugation product is further metabolized and excreted as N -acetyl- S -(propionamide)cysteine (NASPC) in the urine. NASPC could be considered a biomarker for acrylamide exposure. The objective of this study was to develop a highly specific, rapid and sensitive method to quantify urinary NASPC, serving as a biomarker for acrylamide exposure assessment. Isotope-labeled [13C3]NASPC was successfully synthesized and used as an internal standard. This urine mixture was directly analyzed using a newly developed liquid chromatographic/tandem mass spectrometric method coupled with an on-line clean-up system. The detection limit for this method was estimated as <5 µg l,1(0.4 pmol) on-column. The method was applied to measure the urinary level of NASPC in 70 apparently health subjects. The results showed that the NASPC urinary level was highly associated with smoking. Smokers had a significantly higher urinary NASPC level (135 ± 88 µg g,1 creatinine) than non-smokers (76 ± 30 µg g,1 creatinine). A highly sensitive and selective LC/MS/MS isotope dilution method was successfully established. With an on-line clean-up system, this system is capable of routine high-throughput analysis and accurate quantitation of NASPC in urine. This could be a useful tool for health surveillance for acrylamide exposure in a population for future study. Copyright © 2005 John Wiley & Sons, Ltd. [source]

    Lack of protein expression of the simian virus 40 large T antigen in human lymphomas,,

    JOURNAL OF MEDICAL VIROLOGY, Issue 6 2008
    Philip Went
    Abstract Several studies have detected Simian virus 40 (SV40) deoxyribonucleic acid sequences in human tumor tissues, including lymphomas, mainly by the polymerase chain reaction, but these data were not confirmed by subsequent investigations. Regional differences in the distribution of the SV40 and/or technical difficulties have been taken into account to explain these divergent results, but because only a few such studies dealt with the expression of SV40 proteins in tumor tissues, we investigated the expression of the SV40 large T antigen in human lymphomas by immunohistochemistry. Tissue microarrays containing Non-Hodgkin's-lymphomas and Hodgkin's-lymphomas were constructed utilizing archival samples encompassing the years 1974,2001 from Italian, Swiss and Austrian patients. Expression of the SV40 large T antigen was analysed by highly specific and sensitive immunohistochemistry using a mouse monoclonal antibody. Protein expression of the large T antigen was not detected in 655 Non-Hodgkin's-lymphomas or in 337 Hodgkin's- lymphomas. The results suggest the absence of an association between SV40 large T antigen and human lymphomas. J. Med. Virol. 80:1112,1115, 2008. © 2008 Wiley-Liss, Inc. [source]

    Phage display screening for peptidic chitinase inhibitors,

    JOURNAL OF MOLECULAR RECOGNITION, Issue 6 2008
    Cordula Petter
    Abstract A phage display library with disulfide-cyclized peptides was screened for peptides binding to chitinases from Serratia marcescens. One of those peptides was found to efficiently inhibit chitinase A and two others were inhibitors of chitinase B. Complete substitutional analysis of all three peptides using cellulose-bound peptide spot synthesis revealed key interaction positions and allowed optimization of the chitinase B inhibitory peptides towards higher affinity, with inhibitory constants in the lower nanomolar range. Inhibition by all peptides proved to be competitive and highly specific for the chitinase used to select them, as shown with a series of chitinases from different organisms. Copyright © 2008 John Wiley & Sons, Ltd. [source]

    Routine endoscopic retrograde cholangiography in the detection of early biliary complications after liver transplantation

    LIVER TRANSPLANTATION, Issue 5 2002
    Sudeep R. Shah
    The value of routinely performing endoscopic retrograde cholangiography (ERC) to detect biliary complications in patients undergoing orthotopic liver transplantation (OLT) with duct-to-duct anastomosis without a T-tube is not known. Eighty-nine of 171 liver transplant recipients (61 men; mean age, 49.9 years) underwent ERC 14.5 ± 4.5 (SD) days after surgery between January 1997 and August 1999. Findings of ERC and need for intervention for biliary complications were noted. ERC was successful in 71of 89 patients (80%). Nineteen patients (21%) required intervention for biliary complications (stricture, 13 patients; bile leak, 6 patients). Protocol ERC detected eight of these complications (42%). In 4 patients, ERC failed, and 7 patients with a normal ERC result subsequently required intervention (2 patients in the same admission, and 5 patients after discharge). Sensitivity, specificity, and positive and negative predictive values for successful ERC in detecting early biliary complications were 80%, 98%, 89%, and 97%, whereas those for predicting the overall rate of biliary complications were 53%, 98%, 89%, and 89%, respectively. Although highly specific and moderately sensitive in detecting early biliary complications, ERC performed routinely has low sensitivity in predicting the overall risk for biliary complications in patients undergoing OLT with unsplinted duct-to-duct anastomosis. [source]

    In vitro detection of cytotoxic T and NK cells in peripheral blood of patients with various drug-induced skin diseases

    ALLERGY, Issue 3 2010
    A. Zawodniak
    To cite this article: Zawodniak A, Lochmatter P, Yerly D, Kawabata T, Lerch M, Yawalkar N, Pichler WJ. In vitro detection of cytotoxic T and NK cells in peripheral blood of patients with various drug-induced skin diseases. Allergy 2010; 65: 376,384. Abstract Background:, Cytotoxic cells are involved in most forms of drug-induced skin diseases. Till now, no in vitro test addressed this aspect of drug-allergic responses. Our report evaluates whether drug-induced cytotoxic cells can be detected in peripheral blood of nonacute patients with different forms of drug hypersensitivity, and also whether in vitro detection of these cells could be helpful in drug-allergy diagnosis. Methods:, GranzymeB enzyme-linked immunosorbent spot-forming (ELISPOT) and cell surface expression of the degranulation marker CD107a were evaluated on peripheral blood mononuclear cells from 12 drug-allergic patients in remission state and 16 drug-exposed healthy controls. Results:, In 10/12 allergic patients culprit but not irrelevant drug elicited granzymeB release after 48,72 h stimulation. It was clearly positive in patients with high proliferative response to the drug, measured in lymphocyte transformation tests. In patients, who showed moderate or low proliferation and low drug-response in granzymeB ELISPOT, overnight preincubation with interleukin (IL)-7/IL-15 enhanced drug-specific granzymeB release and allowed to clearly identify the offending agent. CD107a staining was positive on CD4+/CD3+, CD8+/CD3+ T cells as well as CD56+/CD3, natural killer cells. None of the drug-exposed healthy donors reacted to the tested drugs and allergic patients reacted only to the offending, but not to tolerated drugs. Conclusion:, GranzymeB ELISPOT is a highly specific in vitro method to detect drug-reacting cytotoxic cells in peripheral blood of drug-allergic patients even several years after disease manifestation. Together with IL-7/IL-15 preincubation, it may be helpful in indentifying the offending drug even in some patients with weak proliferative drug-response. [source]

    Reduced CD4+,CD25, T cell sensitivity to the suppressive function of CD4+,CD25high,CD127,/low regulatory T cells in patients with active systemic lupus erythematosus

    ARTHRITIS & RHEUMATISM, Issue 7 2008
    Ram Kumar Chowdary Venigalla
    Objective CD4+,CD25high regulatory T (Treg) cells play a crucial role in the maintenance of self tolerance and prevention of organ-specific autoimmunity. The presence of many in vivo,preactivated CD4+,CD25++ T cells in patients with systemic lupus erythematosus (SLE) poses a difficulty in discriminating CD25++ activated T cells from CD25high Treg cells. To overcome this problem, we analyzed the phenotype and function of CD4+,CD25high,CD127,/low natural Treg (nTreg) cells isolated from the peripheral blood of patients with SLE. Methods CD4+,CD25high,CD127,/low nTreg cells and CD4+,CD25, responder T (Tresp) cells from patients with SLE and normal donors were separated by fluorescence-activated cell sorting. Cell proliferation was quantified by 3H-thymidine incorporation, and immunophenotyping of the cells was done using FACScan. Results Comparable percentages of CD4+,CD25high,FoxP3+ T cells were observed in patients with SLE and normal donors. Proliferation of SLE nTreg cells sorted into the subset CD4+,CD25high,CD127,/low was significantly decreased compared with that of SLE nTreg cells sorted into the subset CD4+,CD25high (mean ± SEM 2,223 ± 351 counts per minute versus 9,104 ± 1,720 cpm, respectively), while in normal donors, these values were 802 ± 177 cpm and 2,028 ± 548 cpm, respectively, confirming that effector cell contamination was reduced. Notably, the suppressive activity of nTreg cells was intact in all groups. However, CD4+,CD25, Tresp cells isolated from patients with active SLE were significantly less sensitive than those from patients with inactive SLE to the suppressive function of autologous or normal donor CD4+,CD25high,CD127,/low nTreg cells. Furthermore, a significant inverse correlation was observed between the extent of T cell regulation in suppressor assays and the level of lupus disease activity. Conclusion This study is the first to show that, in human SLE, impaired sensitivity of Tresp cells to the suppressive effects of a comparably functional, highly purified nTreg cell population leads to a defective suppression of T cell proliferation in active SLE. Studies aiming to define the mechanisms leading to Tresp cell resistance might help in the development of highly specific, alternative immunotherapeutic tools for the control of systemic autoimmune diseases such as SLE. [source]

    Titration of serum p53 antibodies in 1085 patients with various types of malignant tumors

    CANCER, Issue 3 2003
    A multiinstitutional analysis by the Japan p53 antibody research group
    Abstract BACKGROUND There have been very few large-scale, multiinstitutional studies of surveillance of serum p53 antibodies (S- p53 Abs) in patients with various malignant tumors. METHODS A highly specific, quantitative enzyme-linked immunosorbent assay (ELISA) kit was developed and used to evaluate the efficiency of detecting p53 Abs. A cut-off value was established by analyzing sera from 205 healthy volunteers as reference individuals. Sera from 1085 patients with various types of primary malignant tumors were studied for the presence of S- p53 Abs before treatment. Sera from 34 patients were selected randomly for a competition assay to ensure that antibodies were specific to p53 protein. Carcinoembryonic antigen (CEA) was assessed to compare its positive rate with the positive rate of S- p53 Abs. RESULTS The median value of S- p53 Abs in healthy control individuals was 0.33 U/mL (range, 0.0,4.39 U/mL). Based on reference values that were calculated using parametric determination of the lower 0.95 fraction of the reference distribution in healthy control individuals, the cut-off value was determined as 1.3 U/mL. Two hundred twenty-one of 1085 patients (20.4%) were positive for S- p53 Abs. The highest relevance of S-53 Abs was associated with head and neck carcinoma (32%), followed by esophageal carcinoma (30%), colorectal carcinoma (24%), and carcinoma of the uterus (23%). The positive rate for S- p53 Abs was higher compared with the positive rate for CEA in patients with squamous cell carcinoma. CONCLUSIONS Surveillance of S- p53 Abs is useful in detecting various types of malignant tumors, particular in patients with squamous cell carcinoma. Cancer 2003;97:682,9. © 2003 American Cancer Society. DOI 10.1002/cncr.11092 [source]

    Heparin regulates colon cancer cell growth through p38 mitogen-activated protein kinase signalling

    CELL PROLIFERATION, Issue 1 2010
    G. Chatzinikolaou
    Objectives:, Heparin acts as an extracellular stimulus capable of activating major cell signalling pathways. Thus, we examined the putative mechanisms utilized by heparin to stimulate HT29, SW1116 and HCT116 colon cancer cell growth. Materials and methods:, Possible participation of the mitogen-activated protein kinase (MAPK) cascade on heparin-induced HT29, SW1116 and HCT116 colon cancer cell growth was evaluated using specific MAPK cascade inhibitors, Western blot analysis, real-time quantitative PCR and FACS apoptosis analysis. Results:, Treatment with a highly specific p38 kinase inhibitor, SB203580, significantly (50,70%) inhibited heparin-induced colon cancer cell growth, demonstrating that p38 MAPK signalling is involved in their heparin-induced proliferative response. This was shown to be correlated with increased (up to 3-fold) phosphorylation of 181/182 threonine/tyrosine residues on p38 MAP kinase. Furthermore, heparin inhibited cyclin-dependent kinase inhibitor p21WAF1/CIP1 and p53 tumour suppressor gene and protein expression up to 2-fold or 1.8-fold, respectively, and stimulated cyclin D1 expression up to 1.8-fold, in these cell lines through a p38-mediated mechanism. On the other hand, treatment with heparin did not appear to affect HT29, SW1116 and HCT116 cell levels of apoptosis. Conclusions:, This study demonstrates that an extracellular glycosaminoglycan, heparin, finely modulates expression of genes crucial to cell cycle regulation through specific activation of p38 MAP kinase to stimulate colon cancer cell growth. [source]

    Antibiotic Resistance in Bacteria: Novel Metalloenzyme Inhibitors

    CHEMICAL BIOLOGY & DRUG DESIGN, Issue 4 2009
    Sung-Kun Kim
    ,-Lactam antibiotics are among the most important drugs used to fight bacterial infection. Overuse and misuse of ,-lactam antibiotics has caused the evolution of resistance mechanisms, allowing pathogenic bacteria to survive antibiotic treatment. The major source of resistance to ,-lactam antibiotics occurs through production of enzymes called ,-lactamases capable of catalyzing hydrolysis of the ,-lactam rings in these drug compounds. The metallo-,-lactamases have become a major threat due to their broad substrate specificities; there are no clinically useful inhibitors for these metalloenzymes. We have obtained single-stranded DNA's that are potent inhibitors of the Bacillus cereus 5/B/6 metallo-,-lactamase. These are rapid, reversible, non-competitive inhibitors of the metalloenzyme, with Ki and Ki, values in the nanomolar range. The inhibition patterns and metal ion dependence of their inhibition suggest that the oligonucleotides alter the coordination of the active site metal ion(s); inhibition is efficient and highly specific. Microbiological growth experiments, using combinations of ssDNA with the ,-lactam antibiotic cephalexin, reveal that the inhibitor is capable of causing cell death in liquid cultures of both Gram-positive and Gram-negative metallo-,-lactamase producing bacteria in the micromolar concentration range. [source]