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  1. Article ; Online: Development and Clinical Validation of a Hook Effect-Based Lateral Flow Immunoassay Sensor for Cerebrospinal Fluid Leak Detection.

    Oh, Hyun-Kyung / Park, Jinhee / Sonstein, William J / Maher, Simon / Kim, Min-Gon

    Neurosurgery

    2024  

    Abstract: Background and objectives: Rapid detection of cerebrospinal fluid (CSF) leaks is vital for patient recovery after spinal surgery. However, distinguishing CSF-specific transferrin (TF) from serum TF using lateral flow immunoassays (LFI) is challenging ... ...

    Abstract Background and objectives: Rapid detection of cerebrospinal fluid (CSF) leaks is vital for patient recovery after spinal surgery. However, distinguishing CSF-specific transferrin (TF) from serum TF using lateral flow immunoassays (LFI) is challenging due to their structural similarities. This study aims to develop a novel point-of-care diagnostic assay for precise CSF leak detection by quantifying total TF in both CSF and serum.
    Methods: Capitalizing on the substantial 100-fold difference in TF concentrations between CSF and serum, we designed a diagnostic platform based on the well-known "hook effect" resulting from excessive analyte presence. Clinical samples from 37 patients were meticulously tested using the novel LFI sensor, alongside immunofixation as a reference standard.
    Results: The hook effect-based LFI sensor exhibited outstanding performance, successfully discriminating positive clinical CSF samples from negative ones with remarkable statistical significance (positive vs negative t-test; P = 1.36E-05). This novel sensor achieved an impressive 100% sensitivity and 100% specificity in CSF leak detection, demonstrating its robust diagnostic capabilities.
    Conclusion: In conclusion, our study introduces a rapid, highly specific, and sensitive point-of-care test for CSF leak detection, harnessing the distinctive TF concentration profile in CSF compared with serum. This novel hook effect-based LFI sensor holds great promise for improving patient outcomes in the context of spinal surgery and postsurgical recovery. Its ease of use and reliability make it a valuable tool in clinical practice, ensuring timely and accurate CSF leak detection to enhance patient care.
    Language English
    Publishing date 2024-04-05
    Publishing country United States
    Document type Journal Article
    ZDB-ID 135446-2
    ISSN 1524-4040 ; 0148-396X
    ISSN (online) 1524-4040
    ISSN 0148-396X
    DOI 10.1227/neu.0000000000002914
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Determination of cerebrospinal fluid leakage by selective deletion of transferrin glycoform using an immunochromatographic assay.

    Oh, Jusung / Kwon, Seok-Joon / Dordick, Jonathan S / Sonstein, William J / Linhardt, Robert J / Kim, Min-Gon

    Theranostics

    2019  Volume 9, Issue 14, Page(s) 4182–4191

    Abstract: Cerebrospinal fluid (CSF) leakage can lead to brain and spine pathologies and there is an urgent need for a rapid diagnostic method for determining CSF leakage. Beta-2 transferrin (β2TF), asialotransferrin, is a specific CSF glycoprotein biomarker used ... ...

    Abstract Cerebrospinal fluid (CSF) leakage can lead to brain and spine pathologies and there is an urgent need for a rapid diagnostic method for determining CSF leakage. Beta-2 transferrin (β2TF), asialotransferrin, is a specific CSF glycoprotein biomarker used to determine CSF leakage when distinguished from serum sialotransferrin (sTF).
    MeSH term(s) Cerebrospinal Fluid Leak/diagnosis ; Gold/chemistry ; Humans ; Immunoassay/methods ; Metal Nanoparticles/chemistry ; N-Acetylneuraminic Acid/analysis ; Point-of-Care Testing ; Transferrin/analysis
    Chemical Substances Transferrin ; Gold (7440-57-5) ; N-Acetylneuraminic Acid (GZP2782OP0)
    Language English
    Publishing date 2019-05-31
    Publishing country Australia
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2592097-2
    ISSN 1838-7640 ; 1838-7640
    ISSN (online) 1838-7640
    ISSN 1838-7640
    DOI 10.7150/thno.34411
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Detection of cerebrospinal fluid leakage by specific measurement of transferrin glycoforms

    Kwon, Seok‐Joon / Zhang, Fuming / Dordick, Jonathan S / Sonstein, William J / Linhardt, Robert J

    Electrophoresis. 2015 Oct., v. 36, no. 19

    2015  

    Abstract: A simple and rapid detection of cerebrospinal fluid (CSF) leakage would benefit spine surgeons making critical postoperative decisions on patient care. We have assessed novel approaches to selectively determine CSF β2‐transferrin (β2TF), an asialo‐ ... ...

    Abstract A simple and rapid detection of cerebrospinal fluid (CSF) leakage would benefit spine surgeons making critical postoperative decisions on patient care. We have assessed novel approaches to selectively determine CSF β2‐transferrin (β2TF), an asialo‐transferrin (aTF) biomarker, without interference from serum sialo‐transferrin (sTF) in test samples. First, we performed mild periodate oxidation to selectively generate aldehyde groups in sTF for capture with magnetic hydrazide microparticles, and selective removal with a magnetic separator. Using this protocol sTF was selectively removed from mixtures of CSF and serum containing CSF aTF (β2TF) and serum sTF, respectively. Second, a two‐step enzymatic method was developed with neuraminidase and galactose oxidase for generating aldehyde groups in sTF present in CSF and serum mixtures for magnetic hydrazide microparticle capture. After selectively removing sTF from mixtures of CSF and serum, ELISA could detect significant TF signal only in CSF, while the TF signal in serum was negligible. The new approach for selective removal of only sTF in test samples will be promising for the required intervention by a spine surgeon.
    Keywords biomarkers ; blood serum ; cerebrospinal fluid ; electrophoresis ; enzyme-linked immunosorbent assay ; oxidation ; patient care ; rapid methods ; sialidase ; surgeons ; transferrin
    Language English
    Dates of publication 2015-10
    Size p. 2425-2432.
    Publishing place Verlag Chemie
    Document type Article
    ZDB-ID 619001-7
    ISSN 1522-2683 ; 0173-0835
    ISSN (online) 1522-2683
    ISSN 0173-0835
    DOI 10.1002/elps.201500128
    Database NAL-Catalogue (AGRICOLA)

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  4. Article ; Online: Detection of cerebrospinal fluid leakage by specific measurement of transferrin glycoforms.

    Kwon, Seok-Joon / Zhang, Fuming / Dordick, Jonathan S / Sonstein, William J / Linhardt, Robert J

    Electrophoresis

    2015  Volume 36, Issue 19, Page(s) 2425–2432

    Abstract: A simple and rapid detection of cerebrospinal fluid (CSF) leakage would benefit spine surgeons making critical postoperative decisions on patient care. We have assessed novel approaches to selectively determine CSF β2-transferrin (β2TF), an asialo- ... ...

    Abstract A simple and rapid detection of cerebrospinal fluid (CSF) leakage would benefit spine surgeons making critical postoperative decisions on patient care. We have assessed novel approaches to selectively determine CSF β2-transferrin (β2TF), an asialo-transferrin (aTF) biomarker, without interference from serum sialo-transferrin (sTF) in test samples. First, we performed mild periodate oxidation to selectively generate aldehyde groups in sTF for capture with magnetic hydrazide microparticles, and selective removal with a magnetic separator. Using this protocol sTF was selectively removed from mixtures of CSF and serum containing CSF aTF (β2TF) and serum sTF, respectively. Second, a two-step enzymatic method was developed with neuraminidase and galactose oxidase for generating aldehyde groups in sTF present in CSF and serum mixtures for magnetic hydrazide microparticle capture. After selectively removing sTF from mixtures of CSF and serum, ELISA could detect significant TF signal only in CSF, while the TF signal in serum was negligible. The new approach for selective removal of only sTF in test samples will be promising for the required intervention by a spine surgeon.
    MeSH term(s) Asialoglycoproteins/blood ; Asialoglycoproteins/cerebrospinal fluid ; Asialoglycoproteins/chemistry ; Biomarkers/blood ; Biomarkers/cerebrospinal fluid ; Cerebrospinal Fluid Leak/diagnosis ; Humans ; Sialoglycoproteins/blood ; Sialoglycoproteins/cerebrospinal fluid ; Sialoglycoproteins/chemistry ; Transferrin/analogs & derivatives ; Transferrin/cerebrospinal fluid ; Transferrin/chemistry
    Chemical Substances Asialoglycoproteins ; Biomarkers ; Sialoglycoproteins ; Transferrin ; asialotransferrins ; sialotransferrin, human
    Language English
    Publishing date 2015-10
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 619001-7
    ISSN 1522-2683 ; 0173-0835
    ISSN (online) 1522-2683
    ISSN 0173-0835
    DOI 10.1002/elps.201500128
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Enhanced vascularization and survival of neural transplants with ex vivo angiogenic gene transfer.

    Casper, Diana / Engstrom, Samara J / Mirchandani, Gautam R / Pidel, Ann / Palencia, David / Cho, Paul H / Brownlee, Michael / Edelstein, Diane / Federoff, Howard J / Sonstein, William J

    Cell transplantation

    2002  Volume 11, Issue 4, Page(s) 331–349

    Abstract: Restoration of brain function by neural transplants is largely dependent upon the survival of donor neurons. Unfortunately, in both rodent models and human patients with Parkinson's disease the survival rate of transplanted neurons has been poor. We have ...

    Abstract Restoration of brain function by neural transplants is largely dependent upon the survival of donor neurons. Unfortunately, in both rodent models and human patients with Parkinson's disease the survival rate of transplanted neurons has been poor. We have employed a strategy to increase the availability of nutrients to the transplant by increasing the rate at which blood vessels are formed. Replication-deficient HSV-1 vectors containing the cDNA for human vascular endothelial growth factor (HSVhvegf) and the bacterial beta-galactosidase gene (HSVlac) have been transduced in parallel into nonadherent neuronal aggregate cultures made of cells from embryonic day 15 rat mesencephalon. Gene expression from HSVlac was confirmed in fixed preparations by staining with X-gal. VEGF expression as determined by sandwich ELISA assay of culture supernatant was up to 322-fold higher in HSVhvegf-infected than HSVlac-infected sister cultures. This peptide was also biologically active, inducing endothelial cell proliferation in vitro. Adult Sprague-Dawley rats received bilateral transplants into the striatum, with HSVlac on one side and HSVhvegf on the other. At defined intervals up to 8 weeks, animals were sacrificed and vibratome sections of the striatum were assessed for various parameters of cell survival and vascularization. Results demonstrate dose-dependent increases in blood vessel density within transplants transduced with HSVhvegf. These transplants were vascularized at a faster rate up to 4 weeks after transplantation. After 8 weeks, the average size of the HSVhvegf-infected transplants was twice that of controls. In particular, the survival of transplanted dopaminergic neurons increased 3.9-fold. Taken together these experiments provide convincing evidence that the rate of vascularization may be a major determinant of neuronal survival that can be manipulated by VEGF gene transduction.
    MeSH term(s) Animals ; Brain/blood supply ; Cell Survival ; Cell Transplantation ; DNA, Complementary/metabolism ; Dopamine/metabolism ; Dose-Response Relationship, Drug ; Endothelial Growth Factors/genetics ; Enzyme-Linked Immunosorbent Assay ; Gene Transfer Techniques ; Genetic Vectors ; Herpesvirus 1, Human/metabolism ; Humans ; Immunohistochemistry ; Intercellular Signaling Peptides and Proteins/genetics ; Lac Operon ; Lymphokines/genetics ; Male ; Neovascularization, Physiologic ; Neurons/metabolism ; Parkinson Disease/metabolism ; Rats ; Rats, Sprague-Dawley ; Time Factors ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors
    Chemical Substances DNA, Complementary ; Endothelial Growth Factors ; Intercellular Signaling Peptides and Proteins ; Lymphokines ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors ; Dopamine (VTD58H1Z2X)
    Language English
    Publishing date 2002
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 1135816-6
    ISSN 0963-6897
    ISSN 0963-6897
    Database MEDical Literature Analysis and Retrieval System OnLINE

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