Current insights into functions of phospholipase A2 receptor in normal and cancer cells: More questions than answers.

Lipid signaling network was proposed as a potential target for cancer prevention and treatment. Several recent studies revealed that phospholipid metabolising enzyme, phospholipase A2 (PLA), is a critical regulator of cancer accelerating pathologies and apoptosis in several types of cancers. In addition to functioning as an enzyme, PLA can activate a phospholipase A2 receptor (PLA2R1) in plasma membrane.

Dipping in Ambulatory Blood Pressure Monitoring Correlates With Overnight Urinary Excretion of Catecholamines and Sodium.

Nondipping blood pressure (BP) is associated with increased morbidity and mortality. This study examines the relationship of "dipping" in 24-hour ambulatory BP monitoring (ABPM) with awake and sleeping urinary norepinephrine (NE) and epinephrine (EPI), and that of urinary NE and EPI with urinary sodium (UNa). Fifty nondippers and 65 dippers were included in the present study.

Epigenetic control of group V phospholipase A2 expression in human malignant cells.

Secreted phospholipases A2 (sPLA2) are suggested to play an important role in inflammation and tumorigenesis. Different mechanisms of epigenetic regulation are involved in the control of group IIA, III and X sPLA2s expression in cancer cells, but group V sPLA2 (GV-PLA2) in this respect has not been studied. Here, we demonstrate the role of epigenetic mechanisms in regulation of GV-PLA2 expression in different cell lines originating from leukaemia and solid cancers.

Epigenetic control of phospholipase A2 receptor expression in mammary cancer cells.

Background: It has recently been proposed that the M-type phospholipase A2 receptor (PLA2R1) acts as a tumour suppressor in certain malignancies including mammary cancer. Considering that DNA methylation is an important regulator of gene transcription during carcinogenesis, in the current study we analyzed the PLA2R1 expression, PLA2R1 promoter methylation, and selected micro RNA (miRNA) levels in normal human mammary epithelial cells (HMEC) and cancer cell lines.

Methods: Levels of PLA2R1 and DNA methyltransferases (DNMT) specific mRNA were determined using real-time RT-PCR.

[Effect of autologous platelet concentrates on the anatomical and functional outcome of late stage macular hole surgery: A retrospective analysis].

Background: The macular hole (MH) is a disorder of the visual center of the retina in humans. An untreated MH leads to loss of central visual acuity and reading ability. Surgery for early-stage macular holes has been very successful for many years and leads to very good anatomical and functional results.

Brief Report: Endothelial-Specific X-Box Binding Protein 1 Deficiency Limits Tumor Necrosis Factor-Induced Leukocyte Recruitment and Vasculitis.

Objective: Endothelial cell activation by tumor necrosis factor (TNF) and associated leukocyte infiltration are hallmarks of vasculitis. The aim of this study was to investigate the potential role of the cellular stress-associated endothelial X-box binding protein 1 (XBP-1) transcription factor in TNF-induced endothelial cell inflammation and vasculitis.

Methods: Mice with an endothelial cell-specific XBP-1 deficiency were used in a modified local Shwartzman reaction (LSR) model of TNF-induced small vessel vasculitis.

Coagulation activation after discontinuation of VTE treatment with different oral anticoagulants and impact on 12-month clinical outcomes.

Increasing D-dimer (DD) levels after discontinuation of vitamin K antagonist (VKA) therapy indicate an increased risk of recurrence of venous thromboembolism (VTE). However, after discontinuation of direct-acting non-VKA oral anticoagulants (DOACs or NOACs) the extent of coagulation activation and its clinical impact is unknown. Blood samples were collected from consenting patients with proximal VTE at the end of anticoagulation treatment with apixaban (n=37), dabigatran (n=17), rivaroxaban (n=9) or VKA (n=184) and 4weeks later.

Preservation of urine free catecholamines and their free O-methylated metabolites with citric acid as an alternative to hydrochloric acid for LC-MS/MS-based analyses.

Background: Measurements of urinary fractionated metadrenalines provide a useful screening test to diagnose phaeochromocytoma. Stability of these compounds and their parent catecholamines during and after urine collection is crucial to ensure accuracy of the measurements. Stabilisation with hydrochloric acid (HCl) can promote deconjugation of sulphate-conjugated metadrenalines, indicating a need for alternative preservatives.

Standardized use of novel oral anticoagulants plasma level thresholds in a new thrombolysis decision making protocol.

Acute ischemic stroke (AIS) patients receiving non-vitamin-K antagonist oral anticoagulants (NOAC) are commonly excluded from thrombolytic therapy, as interpretation of coagulation tests remains unclear. We aimed to investigate the applicability of a novel institutional protocol for thrombolysis based on current expert recommendations and NOAC specific coagulation assessment. We included hospitalized AIS patients receiving NOAC for at least 24 h and consecutive AIS patients not receiving NOAC into a prospective study.

The impact of uric acid on long-term mortality in patients with asymptomatic carotid atherosclerotic disease.

Background: Serum uric acid (SUA) has been discussed to be related to cardiovascular (CV) disease and outcome. We investigated whether levels of SUA predict long-term mortality in neurologically asymptomatic patients with carotid atherosclerotic disease.

Methods: We prospectively studied 959 consecutive patients with carotid atherosclerosis as evaluated by duplex Doppler sonography for all-cause and CV death, respectively.

An LC-MS/MS method for steroid profiling during adrenal venous sampling for investigation of primary aldosteronism.

Background: Steroid profiling for diagnosis of endocrine disorders featuring disordered production of steroid hormones is now possible from advances in liquid chromatography with tandem mass spectrometry (LC-MS/MS). Adrenal venous (AV) measurements of aldosterone and cortisol are a standard practice in the clinical work-up of primary aldosteronism, but do not yet take advantage of steroid profiling.

Methods: A novel LC-MS/MS based method was developed for simultaneous measurement of 15 adrenal steroids: aldosterone, corticosterone, 11-deoxycorticosterone, progesterone, pregnenolone, cortisone, cortisol, 11-deoxycortisol, 17-hydroxyprogesterone, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone-sulfate, 21-deoxycortisol, 18-oxocortisol and 18-hydroxycortisol.

A novel pathway of rapid TLR-triggered activation of integrin-dependent leukocyte adhesion that requires Rap1 GTPase.

Rapid β2-integrin activation is indispensable for leukocyte adhesion and recruitment to sites of infection and is mediated by chemokine- or P-selectin glycoprotein ligand-1-induced inside-out signaling. Here we uncovered a novel pathway for rapid activation of integrin-dependent leukocyte adhesion, triggered by toll-like receptor (TLR)-mediated signaling. TLR2 or TLR5 ligation rapidly activated integrin-dependent leukocyte adhesion to immobilized ICAM-1 and fibronectin.

Dual role of B7 costimulation in obesity-related nonalcoholic steatohepatitis and metabolic dysregulation.

Unlabelled: The low-grade inflammatory state present in obesity contributes to obesity-related metabolic dysregulation, including nonalcoholic steatohepatitis (NASH) and insulin resistance. Intercellular interactions between immune cells or between immune cells and hepatic parenchymal cells contribute to the exacerbation of liver inflammation and steatosis in obesity. The costimulatory molecules, B7.

Silibinin down-regulates expression of secreted phospholipase A2 enzymes in cancer cells.

Background: Silibinin, a naturally-occurring flavonoid produced by milk thistle, possesses antioxidant, anti-inflammatory and cancer-preventive activities. In the current study, we examined the effects of silibinin on the expression of secreted phospholipase A2 (sPLA2) enzymes, especially those of group IIA (hGIIA), which play a crucial role in inflammation and carcinogenesis.

Materials And Methods: The effects of silibinin on sPLA2 expressions in human HepG2 hepatoma and PC-3 prostate cancer cells were analyzed using quantitative reverse transcription-polymerase chain reaction and enzyme linked immunosorbent assay technique.

Opposing effects of HIF1α and HIF2α on chromaffin cell phenotypic features and tumor cell proliferation: Insights from MYC-associated factor X.

Pheochromocytomas and paragangliomas (PPGLs) are catecholamine-producing chromaffin cell tumors with diverse phenotypic features reflecting mutations in numerous genes, including MYC-associated factor X (MAX). To explore whether phenotypic differences among PPGLs reflect a MAX-mediated mechanism and opposing influences of hypoxia-inducible factor (HIF)s HIF2α and HIF1α, we combined observational investigations in PPGLs and gene-manipulation studies in two pheochromocytoma cell lines. Among PPGLs from 140 patients, tumors due to MAX mutations were characterized by gene expression profiles and intermediate phenotypic features that distinguished these tumors from other PPGLs, all of which fell into two expression clusters: one cluster with low expression of HIF2α and mature phenotypic features and the other with high expression of HIF2α and immature phenotypic features due to mutations stabilizing HIFs.

Novel parameters of extended complete blood cell count under fluorescence flow cytometry in patients with sepsis.

Background: We first describe a patient who developed urosepsis from an ordinary urinary tract infection. In this case, the new hematological parameters of immature leukocytes, that is, the high-fluorescence lymphocyte cell (HFLC) and immature granulocyte (IG) counts peaked early, whereas the established infection parameters, that is, C-reactive protein (CRP) and total white blood cell count showed less dynamic regarding infection and therapy.

Methods: To investigate this phenomenon in greater detail, the novel parameters HFLC and IG counts are investigated retrospectively in a cohort of 38 patients who were admitted to the anesthesia intensive care unit.

Serum amyloid A, phospholipase A₂-IIA and C-reactive protein as inflammatory biomarkers for prostate diseases.

Introduction: Serum amyloid A (SAA), secreted group IIA phospholipase A₂ (sPLA₂-IIA), and C-reactive protein (CRP) are acute-phase proteins whose serum concentrations increase not only during inflammatory disorders, but also in the course of malignant diseases.

Materials And Methods: In this study we analyzed serum levels of these inflammatory markers along with prostate-specific antigens (PSA) in patients with benign prostatic hyperplasia (BPH, n = 55), localized prostate cancers (PCa, n = 55), and metastatic prostate cancers (mPCa, n = 27) using immunological assays.

Results: We found that in comparison to healthy individuals (n = 55), patients with BPH, PCa and mPCa have elevated serum levels of SAA, sPLA₂-IIA, and CRP, in addition to elevated levels of PSA.

Levodopa therapy in Parkinson's disease: influence on liquid chromatographic tandem mass spectrometric-based measurements of plasma and urinary normetanephrine, metanephrine and methoxytyramine.

Background: Medication-related interferences with measurements of catecholamines and their metabolites represent important causes of false-positive results during diagnosis of phaeochromocytomas and paragangliomas (PPGLs). Such interferences are less troublesome with measurements by liquid chromatography with tandem mass-spectrometry (LC-MS/MS) than by other methods, but can still present problems for some drugs. Levodopa, the precursor for dopamine used in the treatment of Parkinson's disease, represents one potentially interfering medication.

A 3-day delay in synovial fluid crystal identification did not hinder the reliable detection of monosodium urate and calcium pyrophosphate crystals.

Background: Arthrocentesis is an essential emergency step in managing patients with acute arthritis. To identify a bacterial infection, Gram staining is performed promptly. However, crystal analysis may not be immediately performed in many facilities.

Effective estimation of correct platelet counts in pseudothrombocytopenia using an alternative anticoagulant based on magnesium salt.

Pseudothrombocytopenia remains a challenge in the haematological laboratory. The pre-analytical problem that platelets tend to easily aggregate in vitro, giving rise to lower platelet counts, has been known since ethylenediamine-tetra acetic acid EDTA and automated platelet counting procedures were introduced in the haematological laboratory. Different approaches to avoid the time and temperature dependent in vitro aggregation of platelets in the presence of EDTA were tested, but none of them proved optimal for routine purposes.

Plasma levels of phospholipase A2-IIA in patients with different types of malignancies: prognosis and association with inflammatory and coagulation biomarkers.

It is well-known that the plasma level of group IIA phospholipase A2 (sPLA2-IIA) is increased in patients with malignant diseases, but whether the up-regulated enzyme expression is directly related to tumorigenesis or a consequence of tumor-associated inflammation remains unresolved. In this study we analyzed circulating levels of sPLA2-IIA, C-reactive protein (CRP), fibrinogen, factor VIII (FVIII), von Willebrand factor (vWF), and antithrombin as biomarkers of inflammation and coagulation in patients with various types of malignancies. Underlying tumor entities were lung, esophageal, gastric, pancreatic, colorectal, head and neck, and hepatocellular carcinomas as well as multiple myeloma and non-Hodgkin's lymphoma.

Deregulated expression of urokinase and its inhibitor type 1 in prostate cancer cells: role of epigenetic mechanisms.

Plasminogen activator inhibitor-1 (PAI-1) and urokinase-type plasminogen activator (uPA) play a crucial role in cancer progression. In the present study we examined the regulation of PAI-1 and uPA expressions in normal prostate epithelial cells (PrEC) and the prostate cancer cell lines LNCaP, DU-145, and PC-3. The antigen and mRNA levels of PAI-1 were down-regulated in cancer cells, especially in LNCaP and DU-145.

Analysis of plasma 3-methoxytyramine, normetanephrine and metanephrine by ultraperformance liquid chromatography-tandem mass spectrometry: utility for diagnosis of dopamine-producing metastatic phaeochromocytoma.

Background: Measurements of plasma normetanephrine (NMN) and metanephrine (MN) provide a sensitive test for diagnosis of phaeochromocytomas and paragangliomas (PPGLs), but do not allow detection of dopamine-producing tumours. Here we introduce a novel mass spectrometric based method coupled to ultraperformance liquid chromatography (LC-MS/MS) for measuring NMN, MN and 3-methoxytyramine (MTY), the O-methylated metabolite of dopamine.

Methods: Specific collision-induced fragment ions assessed by multireaction monitoring transitions were used for identification, with quantification according to signal intensities of analytes relative to stable isotope labelled internal standards.