Protein Biomarker Identification in the CSF of Patients With CNS Lymphoma

PurposeElucidation of the CSF proteome may yield insights into the pathogenesis of CNS disease. We tested the hypothesis that individual CSF proteins distinguish CNS lymphoma from benign focal brain lesions.MethodsWe used a liquid chromatography/mass spectrometry–based method to differentially quantify and identify several hundred CSF proteins in CNS lymphoma and control patients. We used enzyme-linked immunosorbent assay (ELISA) to confirm one of these markers in an additional validation set of 101 cases.ResultsApproximately 80 CSF proteins were identified and found to be present at significantly different concentrations, both higher and lower, in training and test studies, which were highly concordant. To further validate these observations, we defined in detail the expression of one of these candidate biomarkers, antithrombin III (ATIII). ATIII RNA transcripts were identified within CNS lymphomas, and ATIII protein was localized selectively to tumor neovasculature. Determination of ATIII concentration by ELISA was significantly more accurate (> 75% sensitivity; > 98% specificity) than cytology in the identification of cancer. Measurement of CSF ATIII levels was found to potentially enhance the ability to diagnose and predict outcome.ConclusionOur findings demonstrate for the first time that proteomic analysis of CSF yields individual biomarkers with greater sensitivity in the identification of cancer than does CSF cytology. We propose that the discovery of CSF protein biomarkers will facilitate early and noninvasive diagnosis in patients with lesions not amenable to brain biopsy, as well as provide improved surrogates of prognosis and treatment response in CNS lymphoma and brain metastasis.

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DNA Satellites Are Transcribed as Part of the Non-Coding Genome in Eukaryotes and Bacteria

Genes ◽

10.3390/genes12111651 ◽

2021 ◽

Vol 12 (11) ◽

pp. 1651

Author(s):

Juan A. Subirana ◽

Xavier Messeguer

Keyword(s):

Tandem Repeats ◽

Bacillus Coagulans ◽

C Elegans ◽

Rna Transcripts ◽

New Family ◽

Satellite Rnas ◽

Bacterium Bacillus ◽

And Control ◽

First Time

It has been shown in recent years that many repeated sequences in the genome are expressed as RNA transcripts, although the role of such RNAs is poorly understood. Some isolated and tandem repeats (satellites) have been found to be transcribed, such as mammalian Alu sequences and telomeric/centromeric satellites in different species. However, there is no detailed study on the eventual transcription of the interspersed satellites found in many species. Therefore, we decided to study for the first time the transcription of the abundant DNA satellites in the bacterium Bacillus coagulans and in the nematode Caenorhabditis elegans. We have updated the data for C. elegans satellites using the latest version of the genome. We analyzed the transcription of satellites in both species in available RNA-seq results and found that they are widely transcribed. Our demonstration that satellite RNAs are transcribed adds a new family of non-coding RNAs. This is a field that requires further investigation and will provide a deeper understanding of gene expression and control.

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TBE in Sweden

Tick-borne encephalitis - The Book ◽

10.33442/26613980_12b32-3 ◽

2020 ◽

Keyword(s):

Genetic Characterization ◽

Immunoglobulin M ◽

Enzyme Linked Immunosorbent Assay ◽

Second Phase ◽

Serum Samples ◽

Tick Borne Encephalitis ◽

Specific Immunoglobulin ◽

Tick Borne Encephalitis Virus ◽

First Time

Tick-borne encephalitis virus (TBEV) was isolated for the first time in Sweden in 1958 (from ticks and from 1 tick-borne encephalitis [TBE] patient).1 In 2003, Haglund and colleagues reported the isolation and antigenic and genetic characterization of 14 TBEV strains from Swedish patients (samples collected 1991–1994).2 The first serum sample, from which TBEV was isolated, was obtained 2–10 days after onset of disease and found to be negative for anti-TBEV immunoglobulin M (IgM) by enzyme-linked immunosorbent assay (ELISA), whereas TBEV-specific IgM (and TBEV-specific immunoglobulin G/cerebrospinal fluid [IgG/CSF] activity) was demonstrated in later serum samples taken during the second phase of the disease.

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The Effects of Corporate Ownership on Public Accountants' Professionalism and Ethics

Accounting Horizons ◽

10.2308/acch.2002.16.2.109 ◽

2002 ◽

Vol 16 (2) ◽

pp. 109-124 ◽

Cited By ~ 21

Author(s):

William E. Shafer ◽

D. Jordan Lowe ◽

Timothy J. Fogarty

Keyword(s):

Current Trend ◽

Auditor Independence ◽

Corporate Ownership ◽

Negative Effects ◽

Public Accounting ◽

Corporate Acquisitions ◽

Accounting Professionals ◽

Research Questions ◽

And Control ◽

First Time

The current trend toward corporate acquisitions of CPA firms poses potential threats to the autonomy and ethical standards of public accounting professionals. This recent consolidation movement suggests that for the first time a significant number of public accounting professionals are subject to the supervision and control of nonprofessionals. In addition to acknowledging the potential threats to auditor independence and objectivity, this paper suggests that these new organizational arrangements for the provision of public accounting services have other negative effects on professionalism and ethics such as desensitizing CPAs to traditional professional values, and subverting professional institutions to the goals of corporate employers. This paper develops a framework that identifies several specific research questions related to the effects of corporate ownership on professionalism and ethics in public accounting.

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Plasma Protein Biomarkers Associated with Higher Ovarian Cancer Risk in BRCA1/2 Carriers

Cancers ◽

10.3390/cancers13102300 ◽

2021 ◽

Vol 13 (10) ◽

pp. 2300

Author(s):

Hee-Sung Ahn ◽

Jung Yoon Ho ◽

Jiyoung Yu ◽

Jeonghun Yeom ◽

Sanha Lee ◽

...

Keyword(s):

Ovarian Cancer ◽

Plasma Protein ◽

Normal Subjects ◽

Genetic Alterations ◽

Enzyme Linked Immunosorbent Assay ◽

Ovarian Cancer Risk ◽

Protein Markers ◽

Protein Biomarkers ◽

Proteomics Approach ◽

Risk Reducing

Ovarian cancer (OC) is the most lethal gynecologic malignancy and in-time diagnosis is limited because of the absence of effective biomarkers. Germline BRCA1/2 genetic alterations are risk factors for hereditary OC; risk-reducing salpingo-oophorectomy (RRSO) is pursued for disease prevention. However, not all healthy carriers develop the disease. Therefore, identifying predictive markers in the BRCA1/2 carrier population could help improve the identification of candidates for preventive RRSO. In this study, plasma samples from 20 OC patients (10 patients with BRCA1/2 wild type (wt) and 10 with the BRCA1/2 variant (var)) and 20 normal subjects (10 subjects with BRCA1/2wt and 10 with BRCA1/2var) were analyzed for potential biomarkers of hereditary OC. We applied a bottom-up proteomics approach, using nano-flow LC-MS to analyze depleted plasma proteome quantitatively, and potential plasma protein markers specific to the BRCA1/2 variant were identified from a comparative statistical analysis of the four groups. We obtained 1505 protein candidates from the 40 subjects, and SPARC and THBS1 were verified by enzyme-linked immunosorbent assay. Plasma SPARC and THBS1 concentrations in healthy BRCA1/2 carriers were found to be lower than in OC patients with BRCA1/2var. If plasma SPARC concentrations increase over 337.35 ng/ml or plasma THBS1 concentrations increase over 65.28 mg/ml in a healthy BRCA1/2 carrier, oophorectomy may be suggested.

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The Assessment of IL-21 and IL-22 at the mRNA Level in Tumor Tissue and Protein Concentration in Serum and Peritoneal Fluid in Patients with Ovarian Cancer

Journal of Clinical Medicine ◽

10.3390/jcm10143058 ◽

2021 ◽

Vol 10 (14) ◽

pp. 3058

Author(s):

Aleksandra Mielczarek-Palacz ◽

Celina Kruszniewska-Rajs ◽

Marta Smycz-Kubańska ◽

Jarosław Strzelczyk ◽

Wojciech Szanecki ◽

...

Keyword(s):

Ovarian Cancer ◽

Peritoneal Fluid ◽

Tumor Tissue ◽

Mrna Level ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Expression Of Genes ◽

Genes Encoding ◽

First Time ◽

Ovarian Serous Cancer

The aim of the analysis was for the first time to assess the expression of genes encoding IL-21 and IL-22 at the mRNA level in ovarian tumor specimens and the concentration of these parameters in serum and peritoneal fluid in patients with ovarian serous cancer. The levels of IL-21 and IL-22 transcripts were evaluated with the use of the real-time RT-qPCR. Enzyme-linked immunosorbent assay (ELISA) was used to determine the concentration of proteins. Quantitative analysis of IL-21 gene mRNA in the tumor tissue showed the highest activity in the G1 degree of histopathological differentiation and was higher in G1 compared to the control group. The concentration of IL-21 and IL-22 in the serum and in the peritoneal fluid of women with ovarian cancer varied depending on the degree of histopathological differentiation of the cancer and showed statistical variability compared to controls. The conducted studies have shown that the local and systemic changes in the immune system involving IL-21 and IL-22 indicate the participation of these parameters in the pathogenesis of ovarian cancer, and modulation in the IL-21/IL-22 system may prove useful in the development of new diagnostic and therapeutic strategies used in patients, which require further research.

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Analysis of Risk Factors in Dementia Through Machine Learning

Journal of Alzheimer s Disease ◽

10.3233/jad-200955 ◽

2020 ◽

pp. 1-17

Author(s):

Francisco Javier Balea-Fernandez ◽

Beatriz Martinez-Vega ◽

Samuel Ortega ◽

Himar Fabelo ◽

Raquel Leon ◽

...

Keyword(s):

Machine Learning ◽

Optimization Algorithms ◽

Progressive Increase ◽

Control Group ◽

Data Sets ◽

Modifiable Factors ◽

Validation Set ◽

The One ◽

And Control ◽

Potential Tool

Background: Sociodemographic data indicate the progressive increase in life expectancy and the prevalence of Alzheimer’s disease (AD). AD is raised as one of the greatest public health problems. Its etiology is twofold: on the one hand, non-modifiable factors and on the other, modifiable. Objective: This study aims to develop a processing framework based on machine learning (ML) and optimization algorithms to study sociodemographic, clinical, and analytical variables, selecting the best combination among them for an accurate discrimination between controls and subjects with major neurocognitive disorder (MNCD). Methods: This research is based on an observational-analytical design. Two research groups were established: MNCD group (n = 46) and control group (n = 38). ML and optimization algorithms were employed to automatically diagnose MNCD. Results: Twelve out of 37 variables were identified in the validation set as the most relevant for MNCD diagnosis. Sensitivity of 100%and specificity of 71%were achieved using a Random Forest classifier. Conclusion: ML is a potential tool for automatic prediction of MNCD which can be applied to relatively small preclinical and clinical data sets. These results can be interpreted to support the influence of the environment on the development of AD.

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Comparison of Measurements of Autoantibodies to Glutamic Acid Decarboxylase and Islet Antigen-2 in Whole Blood Eluates from Dried Blood Spots Using the RSR-Enzyme Linked Immunosorbent Assay Kits and In-House Radioimmunoassays

Experimental Diabetes Research ◽

10.1155/2010/173652 ◽

2010 ◽

Vol 2010 ◽

pp. 1-6 ◽

Cited By ~ 4

Author(s):

Anders Persson ◽

Charlotte Becker ◽

Ida Hansson ◽

Anita Nilsson ◽

Carina Törn

Keyword(s):

Glutamic Acid ◽

Glutamic Acid Decarboxylase ◽

Dried Blood Spots ◽

Enzyme Linked Immunosorbent Assay ◽

Acid Decarboxylase ◽

Blood Spots ◽

And Control ◽

Islet Antigen ◽

Prozone Effect

To evaluate the performance of dried blood spots (DBSs) with subsequent analyses of glutamic acid decarboxylase (GADA) and islet antigen-2 (IA-2A) with the RSR-ELISAs, we selected 80 children newly diagnosed with type 1 diabetes and 120 healthy women. DBSs from patients and controls were used for RSR-ELISAs while patients samples were analysed also with in-house RIAs. The RSR-ELISA-GADA performed well with a specificity of 100%, albeit sensitivity (46%) was lower compared to in RIA (56%;P=.008). No prozone effect was observed after dilution of discrepant samples. RSR-ELISA-IA-2A achieved specificity of 69% and sensitivity was lower (59%) compared with RIA (66%;P<.001). Negative or low positive patients and control samples in the RSR-ELISA-IA-2A increased after dilution. Eluates from DBS can readily be used to analyse GADA with the RSR-ELISA, even if low levels of autoantibodies were not detected. Some factor could disturb RSR-ELISA-IA-2A analyses.

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Characterization and protective activity of monoclonal antibodies directed against Fe (3+) ABC transporter substrate-binding protein of Glaesserella parasuis

Veterinary Research ◽

10.1186/s13567-021-00967-1 ◽

2021 ◽

Vol 52 (1) ◽

Author(s):

Kexin Zhu ◽

Dong Yu ◽

Jiahui An ◽

Yufeng Li

Keyword(s):

Monoclonal Antibodies ◽

Abc Transporter ◽

Subunit Vaccine ◽

Binding Protein ◽

Substrate Binding ◽

Passive Immunization ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

And Control ◽

Substrate Binding Protein

AbstractGlässer’s disease is caused by the agent Glaesserella parasuis and is difficult to prevent and control. Candidate screening for subunit vaccines contributes to the prevention of this disease. Therefore, in this study, the inactivated G. parasuis reference serovar 5 strain (G. parasuis-5) was used to generate specific monoclonal antibodies (mAbs) to screen subunit vaccine candidates. Six mAbs (1A12, 3E3, 4C6, 2D1, 3E6, and 4B2) were screened, and they all reacted with the G. parasuis serovar 5 strain according to laser confocal microscopy and flow cytometry (FCM). Indirect enzyme-linked immunosorbent assay (ELISA) showed that one mAb 2D1, can react with all 15 reference serovars of G. parasuis. Protein mass spectrometry and Western blot analysis demonstrated that mAb 2D1 specifically reacts with Fe (3+) ABC transporter substrate-binding protein. A complement killing assay found that the colony numbers of bacteria were significantly reduced in the G. parasuis-5 group incubated with mAb 2D1 (p < 0.01) in comparison with the control group. Opsonophagocytic assays demonstrated that mAb 2D1 significantly enhanced the phagocytosis of 3D4/21 cells by G. parasuis (p < 0.05). RAW264.7 cells with stronger phagocytic ability were also used for the opsonophagocytic assay, and the difference was highly significant (p < 0.01). Passive immunization of mice revealed that mAb 2D1 can eliminate the bacteria in the blood and provide protection against G. parasuis-5. Our study found one mAb that can be used to prevent and control G. parasuis infection in vivo and in vitro, which may suggest that Fe (3+) ABC transporter substrate-binding protein is an immunodominant antigen and a promising candidate for subunit vaccine development.

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Comprehensive Phenotyping in Multiple Sclerosis: Discovery Based Proteomics and the Current Understanding of Putative Biomarkers

Disease Markers ◽

10.1155/2006/670439 ◽

2006 ◽

Vol 22 (4) ◽

pp. 213-225 ◽

Cited By ~ 14

Author(s):

Kevin C. O’Connor ◽

Sushmita Mimi Roy ◽

Christopher H. Becker ◽

David A. Hafler ◽

Aaron B. Kantor

Keyword(s):

Magnetic Resonance Imaging ◽

Multiple Sclerosis ◽

Accurate Diagnosis ◽

Disease Monitoring ◽

Single Test ◽

Resonance Imaging ◽

Control Groups ◽

Csf Proteins ◽

Magnetic Resonance Imaging Mri ◽

And Control

Currently, there is no single test for multiple sclerosis (MS). Diagnosis is confirmed through clinical evaluation, abnormalities revealed by magnetic resonance imaging (MRI), and analysis of cerebrospinal fluid (CSF) chemistry. The early and accurate diagnosis of the disease, monitoring of progression, and gauging of therapeutic intervention are important but elusive elements of patient care. Moreover, a deeper understanding of the disease pathology is needed, including discovery of accurate biomarkers for MS. Herein we review putative biomarkers of MS relating to neurodegeneration and contributions to neuropathology, with particular focus on autoimmunity. In addition, novel assessments of biomarkers not driven by hypotheses are discussed, featuring our application of advanced proteomics and metabolomics for comprehensive phenotyping of CSF and blood. This strategy allows comparison of component expression levels in CSF and serum between MS and control groups. Examination of these preliminary data suggests that several CSF proteins in MS are differentially expressed, and thus, represent putative biomarkers deserving of further evaluation.

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Giving Birth With Epidural Analgesia: The Experience of First-Time Mothers

The Journal of Perinatal Education ◽

10.1891/1058-1243.21.1.24 ◽

2012 ◽

Vol 21 (1) ◽

pp. 24-35 ◽

Cited By ~ 12

Author(s):

Ryoko Hidaka ◽

Lynn Clark Callister

Keyword(s):

Pain Management ◽

Epidural Analgesia ◽

Epidural Administration ◽

Birth Experience ◽

Management Options ◽

Key Factor ◽

Qualitative Descriptive ◽

And Control ◽

First Time ◽

Experiences Of Women

The purpose of our qualitative descriptive study was to describe the birth experiences of women using epidural analgesia for pain management. We interviewed nine primiparas who experienced vaginal births. Five themes emerged: (a) coping with pain, (b) finding epidural administration uneventful, (c) feeling relief having an epidural, (d) experiencing joy, and (e) having unsettled feelings of ambivalence. Although epidural analgesia was found to be effective for pain relief and may contribute to some women’s satisfaction with the birth experience, it does not guarantee a quality birth experience. In order to support and promote childbearing women’s decision making, we recommend improved education on the variety of available pain management options, including their risks and benefits. Fostering a sense of caring, connection, and control in women is a key factor to ensure positive birth experiences, regardless of pain management method.

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