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Proceedings of the Japan Academy.... 2022Extracellular fluids, including blood, lymphatic fluid, and cerebrospinal fluid, are collectively called body fluids. The Na concentration ([Na]) in body fluids is... (Review)
Review
Extracellular fluids, including blood, lymphatic fluid, and cerebrospinal fluid, are collectively called body fluids. The Na concentration ([Na]) in body fluids is maintained at 135-145 mM and is broadly conserved among terrestrial animals. Homeostatic osmoregulation by Na is vital for life because severe hyper- or hypotonicity elicits irreversible organ damage and lethal neurological trauma. To achieve "body fluid homeostasis" or "Na homeostasis", the brain continuously monitors [Na] in body fluids and controls water/salt intake and water/salt excretion by the kidneys. These physiological functions are primarily regulated based on information on [Na] and relevant circulating hormones, such as angiotensin II, aldosterone, and vasopressin. In this review, we discuss sensing mechanisms for [Na] and hormones in the brain that control water/salt intake behaviors, together with the responsible sensors (receptors) and relevant neural pathways. We also describe mechanisms in the brain by which [Na] increases in body fluids activate the sympathetic neural activity leading to hypertension.
Topics: Animals; Body Fluids; Homeostasis; Hormones; Sodium; Sodium Chloride, Dietary; Water
PubMed: 35908954
DOI: 10.2183/pjab.98.016 -
Respirology (Carlton, Vic.) Oct 2019Tuberculous effusion is a common disease entity with a spectrum of presentations from a largely benign effusion, which resolves completely, to a complicated effusion... (Review)
Review
Tuberculous effusion is a common disease entity with a spectrum of presentations from a largely benign effusion, which resolves completely, to a complicated effusion with loculations, pleural thickening and even frank empyema, all of which may have a lasting effect on lung function. The pathogenesis is a combination of true pleural infection and an effusive hypersensitivity reaction, compartmentalized within the pleural space. Diagnostic thoracentesis with thorough pleural fluid analysis including biomarkers such as adenosine deaminase and gamma interferon achieves high accuracy in the correct clinical context. Definitive diagnosis may require invasive procedures to demonstrate histological evidence of caseating granulomas or microbiological evidence of the organism on smear or culture. Drug resistance is an emerging problem that requires vigilance and extra effort to acquire a complete drug sensitivity profile for each tuberculous effusion treated. Nucleic acid amplification tests such as Xpert MTB/RIF can be invaluable in this instance; however, the yield is low in pleural fluid. Treatment consists of standard anti-tuberculous therapy or a guideline-based individualized regimen in the case of drug resistance. There is low-quality evidence that suggests possible benefit from corticosteroids; however, they are not currently recommended due to concomitant increased risk of adverse effects. Small studies report some short- and long-term benefit from interventions such as therapeutic thoracentesis, intrapleural fibrinolytics and surgery but many questions remain to be answered.
Topics: Adenosine Deaminase; Antitubercular Agents; Body Fluids; Drug Resistance, Bacterial; Humans; Interferon-gamma; Pleural Effusion; Thoracentesis; Tuberculosis, Pleural
PubMed: 31418985
DOI: 10.1111/resp.13673 -
Cells Oct 2021Besides their role in cell metabolism, mitochondria display many other functions. Mitochondrial DNA (mtDNA), the own genome of the organelle, plays an important role in... (Review)
Review
Besides their role in cell metabolism, mitochondria display many other functions. Mitochondrial DNA (mtDNA), the own genome of the organelle, plays an important role in modulating the inflammatory immune response. When released from the mitochondrion to the cytosol, mtDNA is recognized by cGAS, a cGAMP which activates a pathway leading to enhanced expression of type I interferons, and by NLRP3 inflammasome, which promotes the activation of pro-inflammatory cytokines Interleukin-1beta and Interleukin-18. Furthermore, mtDNA can be bound by Toll-like receptor 9 in the endosome and activate a pathway that ultimately leads to the expression of pro-inflammatory cytokines. mtDNA is released in the extracellular space in different forms (free DNA, protein-bound DNA fragments) either as free circulating molecules or encapsulated in extracellular vesicles. In this review, we discussed the latest findings concerning the molecular mechanisms that regulate the release of mtDNA from mitochondria, and the mechanisms that connect mtDNA misplacement to the activation of inflammation in different pathophysiological conditions.
Topics: Biological Evolution; Body Fluids; DNA, Mitochondrial; Extracellular Vesicles; Humans; Inflammasomes; Inflammation
PubMed: 34831121
DOI: 10.3390/cells10112898 -
Nature Medicine Jan 2021We developed a metagenomic next-generation sequencing (mNGS) test using cell-free DNA from body fluids to identify pathogens. The performance of mNGS testing of...
We developed a metagenomic next-generation sequencing (mNGS) test using cell-free DNA from body fluids to identify pathogens. The performance of mNGS testing of 182 body fluids from 160 patients with acute illness was evaluated using two sequencing platforms in comparison to microbiological testing using culture, 16S bacterial PCR and/or 28S-internal transcribed ribosomal gene spacer (28S-ITS) fungal PCR. Test sensitivity and specificity of detection were 79 and 91% for bacteria and 91 and 89% for fungi, respectively, by Illumina sequencing; and 75 and 81% for bacteria and 91 and 100% for fungi, respectively, by nanopore sequencing. In a case series of 12 patients with culture/PCR-negative body fluids but for whom an infectious diagnosis was ultimately established, seven (58%) were mNGS positive. Real-time computational analysis enabled pathogen identification by nanopore sequencing in a median 50-min sequencing and 6-h sample-to-answer time. Rapid mNGS testing is a promising tool for diagnosis of unknown infections from body fluids.
Topics: Adult; Aged; Bacteria; Body Fluids; Cell-Free Nucleic Acids; Female; Fungi; High-Throughput Nucleotide Sequencing; Humans; Male; Metagenomics; Middle Aged
PubMed: 33169017
DOI: 10.1038/s41591-020-1105-z -
International Journal of Molecular... Sep 2019Diabetic retinopathy (DR), a sight-threatening neurovasculopathy, is the leading cause of irreversible blindness in the developed world. DR arises as the result of... (Review)
Review
Diabetic retinopathy (DR), a sight-threatening neurovasculopathy, is the leading cause of irreversible blindness in the developed world. DR arises as the result of prolonged hyperglycemia and is characterized by leaky retinal vasculature, retinal ischemia, retinal inflammation, angiogenesis, and neovascularization. The number of DR patients is growing with an increase in the elderly population, and therapeutic approaches are limited, therefore, new therapies to prevent retinal injury and enhance repair are a critical unmet need. Besides vascular endothelial growth factor (VEGF)-induced vascular proliferation, several other mechanisms are important in the pathogenesis of diabetic retinopathy, including vascular inflammation. Thus, combining anti-VEGF therapy with other new therapies targeting these pathophysiological pathways of DR may further optimize treatment outcomes. Technological advancements have allowed for high-throughput proteomic studies examining biofluids such as aqueous humor, vitreous humor, tear, and serum. Many DR biomarkers have been identified, especially proteins involved in retinal inflammatory processes. This review attempts to summarize the proteomic biomarkers of DR-associated retinal inflammation identified over the last several years.
Topics: Biomarkers; Body Fluids; Diabetic Retinopathy; Humans; Protein Processing, Post-Translational; Proteome; Proteomics; Retinitis
PubMed: 31557880
DOI: 10.3390/ijms20194755 -
Cytometry. Part B, Clinical Cytometry May 2021Flow cytometric detection of T-cell clonality is challenging. The current available methodology for T-cell receptor (TCR) Vβ repertoire evaluation is a complex assay...
Flow cytometric evaluation of TRBC1 expression in tissue specimens and body fluids is a novel and specific method for assessment of T-cell clonality and diagnosis of T-cell neoplasms.
BACKGROUND
Flow cytometric detection of T-cell clonality is challenging. The current available methodology for T-cell receptor (TCR) Vβ repertoire evaluation is a complex assay and has limited sensitivity especially for detecting low levels of disease. Therefore, there is an unmet need for a reliable, simple, and rapid assay to identify T-cell clonality. The rearrangement of the TCRB gene involves the random and mutually exclusive expression of one of two constant β chain genes (TRBC1 and TRBC2), analogous to the kappa and lambda gene utilization by B cells.
METHODS
Here, we used a single TRBC1 antibody, in conjunction with other T-cell associated markers, to detect T-cell clonality in tissue biopsies and body fluids. A total of 143 tissue/body fluid specimens from 46 patients with a definitive diagnosis of a T-cell neoplasm and 97 patients with no T-cell malignancy were analyzed with a cocktail of monoclonal antibodies including CD2/CD3/CD4/CD5/CD7/CD8/CD45/TCRγδ/TRBC1.
RESULTS
We examined TRBC1 expression on neoplastic T-cell populations identified based on their immunophenotypic aberrancies, and monotypic TRBC1 expression was identified in all 46 known T-cell lymphoma cases. We applied a similar gating strategy to the 97 cases without T-cell neoplasms, and arbitrarily dissected T-cell populations into immunophenotypically distinct subsets; in this group, we found that all cases revealed an expected polytypic TRBC1 expression in all subsets.
CONCLUSIONS
Single TRBC1 antibody detection of T-cell clonality by flow cytometry is a simple, rapid, and robust assay that could be routinely utilized in flow cytometric laboratories.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Body Fluids; Female; Flow Cytometry; Humans; Immunophenotyping; Lymphoma, T-Cell; Male; Middle Aged; Receptors, Antigen, T-Cell, alpha-beta; Receptors, Antigen, T-Cell, gamma-delta; T-Lymphocytes; Young Adult
PubMed: 32333725
DOI: 10.1002/cyto.b.21881 -
Molecular & Cellular Proteomics : MCP Jul 2023Accurate biomarkers are a crucial and necessary precondition for precision medicine, yet existing ones are often unspecific and new ones have been very slow to enter the...
Accurate biomarkers are a crucial and necessary precondition for precision medicine, yet existing ones are often unspecific and new ones have been very slow to enter the clinic. Mass spectrometry (MS)-based proteomics excels by its untargeted nature, specificity of identification, and quantification, making it an ideal technology for biomarker discovery and routine measurement. It has unique attributes compared to affinity binder technologies, such as OLINK Proximity Extension Assay and SOMAscan. In in a previous review in 2017, we described technological and conceptual limitations that had held back success. We proposed a 'rectangular strategy' to better separate true biomarkers by minimizing cohort-specific effects. Today, this has converged with advances in MS-based proteomics technology, such as increased sample throughput, depth of identification, and quantification. As a result, biomarker discovery studies have become more successful, producing biomarker candidates that withstand independent verification and, in some cases, already outperform state-of-the-art clinical assays. We summarize developments over the last years, including the benefits of large and independent cohorts, which are necessary for clinical acceptance. Shorter gradients, new scan modes, and multiplexing are about to drastically increase throughput, cross-study integration, and quantification, including proxies for absolute levels. We have found that multiprotein panels are inherently more robust than current single analyte tests and better capture the complexity of human phenotypes. Routine MS measurement in the clinic is fast becoming a viable option. The full set of proteins in a body fluid (global proteome) is the most important reference and the best process control. Additionally, it increasingly has all the information that could be obtained from targeted analysis although the latter may be the most straightforward way to enter regular use. Many challenges remain, not least of a regulatory and ethical nature, but the outlook for MS-based clinical applications has never been brighter.
Topics: Humans; Proteomics; Mass Spectrometry; Biomarkers; Proteome; Body Fluids
PubMed: 37209816
DOI: 10.1016/j.mcpro.2023.100577 -
Cancer Cytopathology Mar 2022Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for coronavirus disease 2019 (COVID-19), is known to cause severe respiratory...
BACKGROUND
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for coronavirus disease 2019 (COVID-19), is known to cause severe respiratory infections with occasional accompanying pleural effusion (PE), pericardial effusion (PCE), or peritoneal effusion (PTE). The effect of COVID-19 on effusion cytology is not yet known. This study aimed to examine the cytomorphologic features and workup of effusion fluids in patients with active COVID-19 infection versus those in recovery.
METHODS
PE (n = 15), PCE (n = 1), and PTE samples (n = 20) from hospitalized patients with a SARS-CoV-2 infection (from June 1, 2020, to December 30, 2020) were reviewed. Effusion fluids with metastatic carcinoma were excluded. Differential cell counts, cytomorphology, and relevant immunostains for effusion fluids were retrospectively evaluated and compared between patients with active infection (positive on a SARS-CoV-2 nucleic acid amplification test [NAAT] within 2 months; n = 23) and those in the recovery phase from COVID-19 (negative on a SARS-CoV-2 NAAT for >2 months; n = 13).
RESULTS
The cytology diagnoses were negative for malignancy (n = 31), atypical (n = 4), and suspicious for malignancy (n = 1). Active infection cases showed more atypical mesothelial cells than recovery cases (P < .05); some had enlarged nuclei, prominent nucleoli, occasional multinucleation, and bizarre nuclei. Immunostains were performed more often in active infection cases than recovery cases (47.8% vs 7.7%; P < .05). Differential cell counts (available for 28 cases) showed no significant differences between the active infection and recovery groups.
CONCLUSIONS
This study found atypical and bizarre mesothelial cells more often in effusions of cases with active COVID-19 infection in comparison with patients in recovery. It is important for cytopathologists to become familiar with the cytomorphologic effects of SARS-CoV-2 on effusion cytology so that these cases can be properly triaged.
Topics: Body Fluids; COVID-19; Cytodiagnosis; Humans; Retrospective Studies; SARS-CoV-2
PubMed: 34958719
DOI: 10.1002/cncy.22545 -
BioMed Research International 2021The novel coronavirus disease 2019 (COVID-19) is the cause of an acute respiratory illness which has spread around the world. The virus infects the host by binding to... (Review)
Review
The novel coronavirus disease 2019 (COVID-19) is the cause of an acute respiratory illness which has spread around the world. The virus infects the host by binding to the angiotensin-converting enzyme 2 (ACE2) receptors. Due to the presence of ACE2 receptors in the kidneys and gastrointestinal (GI) tract, kidneys and GI tract damage arising from the virus can be seen in patients and can cause acute conditions such as acute kidney injury (AKI) and digestive problems for the patient. One of the complications of kidneys and GI involvement in COVID-19 is fluid and electrolyte disturbances. The most common ones of these disorders are hyponatremia, hypernatremia, hypokalemia, hypocalcemia, hypochloremia, hypervolemia, and hypovolemia, which if left untreated, cause many problems for patients and even increase mortality. Fluid and electrolyte disturbances are more common in hospitalized and intensive care patients. Children are also at greater risk for fluid and electrolyte disturbances complications. Therefore, clinicians should pay special attention to the fluid and electrolyte status of patients. Changes in fluid and electrolyte levels can be a good indicator of disease progression.
Topics: Acute Kidney Injury; Body Fluids; COVID-19; Electrolytes; Gastrointestinal Tract; Humans; Hypocalcemia; Hypokalemia; Hyponatremia; Kidney
PubMed: 33937408
DOI: 10.1155/2021/6667047 -
Briefings in Bioinformatics Jan 2021Empowered by the advancement of high-throughput bio technologies, recent research on body-fluid proteomes has led to the discoveries of numerous novel disease biomarkers... (Review)
Review
Empowered by the advancement of high-throughput bio technologies, recent research on body-fluid proteomes has led to the discoveries of numerous novel disease biomarkers and therapeutic drugs. In the meantime, a tremendous progress in disclosing the body-fluid proteomes was made, resulting in a collection of over 15 000 different proteins detected in major human body fluids. However, common challenges remain with current proteomics technologies about how to effectively handle the large variety of protein modifications in those fluids. To this end, computational effort utilizing statistical and machine-learning approaches has shown early successes in identifying biomarker proteins in specific human diseases. In this article, we first summarized the experimental progresses using a combination of conventional and high-throughput technologies, along with the major discoveries, and focused on current research status of 16 types of body-fluid proteins. Next, the emerging computational work on protein prediction based on support vector machine, ranking algorithm, and protein-protein interaction network were also surveyed, followed by algorithm and application discussion. At last, we discuss additional critical concerns about these topics and close the review by providing future perspectives especially toward the realization of clinical disease biomarker discovery.
Topics: Biomarkers; Body Fluids; Humans; Proteome; Proteomics
PubMed: 32020158
DOI: 10.1093/bib/bbz160