scholarly journals Different Metabolomic and Proteomic Profiles of Cerebrospinal Fluid in Ventricular and Lumbar Compartments in Relation to Leptomeningeal Metastases

Metabolites ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 80
Author(s):  
Ji-Woong Kwon ◽  
Ji Hye Im ◽  
Kyue-Yim Lee ◽  
Byong Chul Yoo ◽  
Jun Hwa Lee ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Coagulation Factor ◽  
Proteome Analysis ◽  
Leptomeningeal Metastasis ◽  
Complement C3 ◽  
Factor V ◽  
Protein Profiles ◽  
Metabolome Analysis ◽  
Gamma Chain ◽  
Low Mass

The different molecular profiles of cerebrospinal fluid (CSF) between ventricular and lumbar compartments remain elusive, especially in the context of leptomeningeal metastasis (LM), which affects CSF flow. We evaluated CSF metabolomic and proteomic profiles based on the compartments and the diagnosis of spinal LM, proved by MRI from 20 paired ventricular and lumbar CSF samples of LM patients, including 12 spinal LM (+) samples. In metabolome analysis, 9512 low-mass ions (LMIs) were identified—7 LMIs were abundant in all lumbar versus paired ventricular CSF samples, and 3 LMIs were significantly abundant in all ventricular CSF. In comparisons between spinal LM (+) CSF and LM (−) CSF, 105 LMIs were discriminative for spinal LM (+) CSF. In proteome analysis, a total of 1536 proteins were measured. A total of 18 proteins, including complement C3, were more highly expressed in all lumbar CSF, compared with paired ventricular CSF, while 82 proteins, including coagulation factor V, were higher in the ventricular CSF. Of 37 discriminative proteins, including uteroglobin and complement component C8 gamma chain, 4 were higher in all spinal LM (+) CSF versus spinal LM (−) CSF. We further evaluated metabolic pathways associated with these discriminative proteins using the Gene Ontology database. We found that 16/17 spinal LM (+) pathways, including complement activation, were associated with lumbar discriminative proteins, whereas only 2 pathways were associated with ventricular-discriminative proteins. In conclusion, we determined that metabolite and protein profiles differed between paired lumbar and ventricular CSF samples. The protein profiles of spinal LM (+) CSF showed more similarity with the lumbar CSF than the ventricular CSF. Thus, we suggest that CSF LMIs and proteins could reflect LM disease activity and that LM-associated differences in CSF are more likely to be present in the lumbar compartment.

scholarly journals Cerebrospinal Fluid Biomarkers of Japanese Encephalitis

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 334
Author(s):  
Nabonita Sengupta ◽  
Sriparna Mukherjee ◽  
Piyush Tripathi ◽  
Rashmi Kumar ◽  
Amol Ratnakar Suryawanshi ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Japanese Encephalitis ◽  
Clinical Manifestations ◽  
Complement C3 ◽  
Gamma Chain ◽  
Acute Encephalitis ◽  
Cerebrospinal Fluid Biomarkers ◽  
Wide Range ◽  
2D Gel ◽  
Biomarker Research

Japanese encephalitis (JE) is the leading cause of viral encephalitis in Asia. Acute encephalitis syndrome (AES) is a group of central nervous system (CNS) disorders caused by a wide range of viruses, bacteria, fungi, chemicals and toxins. It is important to distinguish between various forms of infectious encephalitis with similar clinical manifestations in order to ensure specific and accurate diagnosis and development of subsequent therapeutic strategies. Cerebrospinal fluid (CSF) is in direct contact with the CNS and hence it is considered to be an excellent source for identifying biomarkers for various neurological disorders. With the recent advancement in proteomic methodologies, the field of biomarker research has received a remarkable boost.  The present study identifies potential biomarkers for JE using a proteomics based approach. The CSF proteomes from ten patients each with JE and Non-JE acute encephalitis were analyzed by 2D gel electrophoresis followed by mass spectrometry. Vitamin D-binding protein (DBP), fibrinogen gamma chain, fibrinogen beta chain, complement C4-B, complement C3 and cytoplasmic actin were found to be significantly elevated in case of JE indicating severe disruption of the blood brain barrier and DBP can be suggested to be an important diagnostic marker.

scholarly journals Experimental Assessment of Leptomeningeal Metastasis Diagnosis in Medulloblastoma Using Cerebrospinal Fluid Metabolomic Profiles

Metabolites ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 851
Author(s):  
Ji Hye Im ◽  
Byong Chul Yoo ◽  
Jun Hwa Lee ◽  
Kyue-Yim Lee ◽  
Kyung-Hee Kim ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Diagnostic Accuracy ◽  
Leptomeningeal Metastasis ◽  
Test Results ◽  
Liquid Chromatography Mass Spectrometry ◽  
Csf Cytology ◽  
Resonance Imaging ◽  
Diagnostic Potential ◽  
Low Mass ◽  
Magnetic Resonance Imaging Mri

Diagnosing leptomeningeal metastasis (LM) in medulloblastoma is currently based on positive cerebrospinal fluid (CSF) cytology or magnetic resonance imaging (MRI) finding. However, the relevance of discordant results has not been established. We evaluated the diagnostic potential of CSF metabolomic profiles in the medulloblastoma LM assessment. A total of 83 CSF samples from medulloblastoma patients with documented MRI and CSF cytology results at the time of sampling for LM underwent low-mass ions (LMIs) analysis using liquid chromatography-mass spectrometry. Discriminating LMIs were selected by a summed sensitivity and specificity (>160%) and LMI discriminant equation (LOME) algorithms, evaluated by measuring diagnostic accuracy for verifying LM groups of different MRI/cytology results. Diagnostic accuracy of LM in medulloblastoma was 0.722 for cytology and 0.889 for MRI. Among 6572 LMIs identified in all sample, we identified 27 discriminative LMIs differentiating MRI (+)/cytology (+) from MRI (−)/cytology (−). Using LMI discriminant equation (LOME) analysis, we selected 9 LMIs with a sensitivity of 100% and a specificity of 93.6% for differentiating MRI (+)/cytology (+) from MRI (−)/cytology (−). Another LOME of 20 LMIs significantly differentiated sampling time relative to treatment (p = 0.007) and the presence or absence of LM-related symptoms (p = 0.03) in the MRI (+)/cytology (−) group. CSF metabolomics of medulloblastoma patients revealed significantly different profiles among LM diagnosed with different test results. We suggest that LM patients could be screened by appropriately selected LOME-generated LMIs to support LM diagnosis by either MRI or cytology alone.

scholarly journals Cerebrospinal Fluid Biomarkers of Japanese Encephalitis

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 334 ◽  
Author(s):  
Nabonita Sengupta ◽  
Sriparna Mukherjee ◽  
Piyush Tripathi ◽  
Rashmi Kumar ◽  
Amol Ratnakar Suryawanshi ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Japanese Encephalitis ◽  
Clinical Manifestations ◽  
Complement C3 ◽  
Gamma Chain ◽  
Acute Encephalitis ◽  
Cerebrospinal Fluid Biomarkers ◽  
Wide Range ◽  
2D Gel ◽  
Biomarker Research

Japanese encephalitis (JE) is the leading cause of viral encephalitis in Asia. Acute encephalitis syndrome (AES) is a group of central nervous system (CNS) disorders caused by a wide range of viruses, bacteria, fungi, chemicals and toxins. It is important to distinguish between various forms of infectious encephalitis with similar clinical manifestations in order to ensure specific and accurate diagnosis and development of subsequent therapeutic strategies. Cerebrospinal fluid (CSF) is in direct contact with the CNS and hence it is considered to be an excellent source for identifying biomarkers for various neurological disorders. With the recent advancement in proteomic methodologies, the field of biomarker research has received a remarkable boost.  The present study identifies potential biomarkers for JE using a proteomics based approach. The CSF proteomes from ten patients each with JE and Non-JE acute encephalitis were analyzed by 2D gel electrophoresis followed by mass spectrometry. Vitamin D-binding protein (DBP), fibrinogen gamma chain, fibrinogen beta chain, complement C4-B, complement C3 and cytoplasmic actin were found to be significantly elevated in case of JE indicating severe disruption of the blood brain barrier and DBP can be suggested to be an important diagnostic marker.

Proteome analysis of cerebrospinal fluid in patients with Multiple System Atrophy (MSA)

2008 ◽  
Vol 35 (S 01) ◽  
Author(s):  
S Werz ◽  
V Lehmensiek ◽  
S Süssmuth ◽  
H Mogel ◽  
J Brettschneider ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Multiple System Atrophy ◽  
Proteome Analysis

Coagulation Factor V Leiden Mutation Was Detected in the Patients with Activated Protein C Resistance in Thailand

1998 ◽  
Vol 80 (08) ◽  
pp. 344-345 ◽  
Author(s):  
Pasra Arnutti ◽  
Motofumi Hiyoshi ◽  
Wichai Prayoonwiwat ◽  
Oytip Nathalang ◽  
Chamaiporn Suwanasophon ◽  
...  
Keyword(s):  
Protein C ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Coagulation Factor ◽  
Factor V ◽  
Activated Protein C Resistance ◽  
Factor V Leiden Mutation ◽  
Coagulation Factor V

Ancylostoma caninum Anticoagulant Peptide Blocks Metastasis In Vivo and Inhibits Factor Xa Binding to Melanoma Cells In Vitro

1998 ◽  
Vol 79 (05) ◽  
pp. 1041-1047 ◽  
Author(s):  
Kathleen M. Donnelly ◽  
Michael E. Bromberg ◽  
Aaron Milstone ◽  
Jennifer Madison McNiff ◽  
Gordon Terwilliger ◽  
...  
Keyword(s):  
Active Site ◽  
Thrombin Generation ◽  
Factor Xa ◽  
Coagulation Factor ◽  
Melanoma Cells ◽  
Factor V ◽  
Ancylostoma Caninum ◽  
Metastatic Activity

SummaryWe evaluated the in vivo anti-metastatic activity of recombinant Ancylostoma caninum Anticoagulant Peptide (rAcAP), a potent (Ki = 265 pM) and specific active site inhibitor of human coagulation factor Xa originally isolated from bloodfeeding hookworms. Subcutaneous injection of SCID mice with rAcAP (0.01-0.2 mg/mouse) prior to tail vein injection of LOX human melanoma cells resulted in a dose dependent reduction in pulmonary metastases. In order to elucidate potential mechanisms of rAcAP’s anti-metastatic activity, experiments were carried out to identify specific interactions between factor Xa and LOX. Binding of biotinylated factor Xa to LOX monolayers was both specific and saturable (Kd = 15 nM). Competition experiments using antibodies to previously identified factor Xa binding proteins, including factor V/Va, effector cell protease receptor-1, and tissue factor pathway inhibitor failed to implicate any of these molecules as significant binding sites for Factor Xa. Functional prothrombinase activity was also supported by LOX, with a half maximal rate of thrombin generation detected at a factor Xa concentration of 2.4 nM. Additional competition experiments using an excess of either rAcAP or active site blocked factor Xa (EGR-Xa) revealed that most of the total factor Xa binding to LOX is mediated via interaction with the enzyme’s active site, predicting that the vast majority of cell-associated factor Xa does not participate directly in thrombin generation. In addition to establishing two distinct mechanisms of factor Xa binding to melanoma, these data raise the possibility that rAcAP’s antimetastatic effect in vivo might involve novel non-coagulant pathways, perhaps via inhibition of active-site mediated interactions between factor Xa and tumor cells.

Phenotyping and Genotyping of Coagulation Factor V Leiden

1996 ◽  
Vol 75 (02) ◽  
pp. 267-269 ◽  
Author(s):  
H Engel ◽  
L Zwang ◽  
H H D M van Vliet ◽  
J J Michiles ◽  
J Stibbe ◽  
...  
Keyword(s):  
Factor V Leiden ◽  
Coagulation Factor ◽  
Diagnostic Value ◽  
Resistance Test ◽  
Amplification Refractory Mutation System ◽  
Factor V ◽  
Chain Reactions ◽  
Apc Resistance ◽  
Specificity And Sensitivity ◽  
Coagulation Factor V

SummaryThe currently used activated Protein C resistance test demonstrated to be of limited diagnostic value for the detection of the mutant Factor V Leiden. Moreover, this assay is not useful for patients under anticoagulant therapy. A modification of the APC resistance test, applying Factor V deficient plasma is described which demonstrates a specificity and sensitivity of 1.0. The superiority of the modified APC resistance test over the existing APC resistance test was verified by genotyping.For that purpose, the Amplification Refractory Mutation System (ARMS) was applied to the detection of the G to A mutation at position 1691 in the gene encoding coagulation Factor V. The mutation at that position could be easily detected by using each of two allele-specific oligonucleotide primers concomitantly with one common primer in two separate polymerase chain reactions, thereby amplifying a fragment of 186 base-pairs of the Factor V gene.

Coagulation Factor V: An Old Star Shines Again

1997 ◽  
Vol 78 (01) ◽  
pp. 427-433 ◽  
Author(s):  
Jan Rosing ◽  
Guido Tans
Keyword(s):  
Coagulation Factor ◽  
Factor V ◽  
Coagulation Factor V

scholarly journals Proteomic characterisations of ulcerative colitis endoscopic biopsies associate with clinically relevant histological measurements of disease severity

2021 ◽  
pp. jclinpath-2021-207718
Author(s):  
Aaron M Gruver ◽  
Matt D Westfall ◽  
Bradley L Ackermann ◽  
Salisha Hill ◽  
Ryan D Morrison ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Accuracy Assessment ◽  
Interleukin 2 ◽  
Proteome Analysis ◽  
Scoring Systems ◽  
Cell Junction ◽  
Interleukin 17 ◽  
Gamma Chain ◽  
Novel Approach ◽  
Interleukin 23

Aims and methodsAccurate protein measurements using formalin-fixed biopsies are needed to improve disease characterisation. This feasibility study used targeted and global mass spectrometry (MS) to interrogate a spectrum of disease severities using 19 ulcerative colitis (UC) biopsies.ResultsTargeted assays for CD8, CD19, CD132 (interleukin-2 receptor subunit gamma/common cytokine receptor gamma chain), FOXP3 (forkhead box P3) and IL17RA (interleukin 17 receptor A) were successful; however, assays for IL17A (interleukin 17A), IL23 (p19) (interleukin 23, alpha subunit p19) and IL23R (interleukin 23 receptor) did not permit target detection. Global proteome analysis (4200 total proteins) was performed to identify pathways associated with UC progression. Positive correlation was observed between histological scores indicating active colitis and neutrophil-related measurements (R2=0.42–0.72); inverse relationships were detected with cell junction targets (R2=0.49–0.71) and β-catenin (R2=0.51–0.55) attributed to crypt disruption. An exploratory accuracy assessment with Geboes Score and Robarts Histopathology Index cut-offs produced sensitivities/specificities of 72.7%/75.0% and 100.0%/81.8%, respectively.ConclusionsPathologist-guided MS assessments provide a complementary approach to histological scoring systems. Additional studies are indicated to verify the utility of this novel approach.

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