Activation of 2-oxoglutarate receptor 1 (OXGR1) by α-ketoglutarate (αKG) does not detectably stimulate Pendrin-mediated anion exchange in Xenopus oocytes.

SLC26A4/Pendrin is the major electroneutral Cl /HCO exchanger of the apical membrane of the Type B intercalated cell (IC) of the connecting segment (CNT) and cortical collecting duct (CCD). Pendrin mediates both base secretion in response to systemic base load and Cl reabsorption in response to systemic volume depletion, manifested as decreased nephron salt and water delivery to the distal nephron. Pendrin-mediated Cl /HCO exchange in the apical membrane is upregulated through stimulation of the β-IC apical membrane G protein-coupled receptor, 2-oxoglutarate receptor 1 (OXGR1/GPR99), by its ligand α-ketoglutarate (αKG).

The erythroid K-Cl cotransport inhibitor [(dihydroindenyl)oxy]acetic acid blocks erythroid Ca-activated K channel KCNN4.

Red cell volume is a major determinant of HbS concentration in sickle cell disease. Cellular deoxy-HbS concentration determines the delay time, the interval between HbS deoxygenation and deoxy-HbS polymerization. Major membrane transporter protein determinants of sickle red cell volume include the SLC12/KCC K-Cl cotransporters KCC3/SLC12A6 and KCC1/SLC12A4, and the KCNN4/KCa3.

Dysregulated Erythroid Mg Efflux in Type 2 Diabetes.

Hyperglycemia is associated with decreased Mg content in red blood cells (RBC), but mechanisms remain unclear. We characterized the regulation of Mg efflux by glucose in human RBC. We observed that hemoglobin A (HbA) values correlated with Na-dependent Mg efflux (Na/Mg exchange) and inversely correlated with cellular Mg content.

Erythroid-specific inactivation of Slc12a6/Kcc3 by EpoR promoter-driven Cre expression reduces K-Cl cotransport activity in mouse erythrocytes.

Investigation of erythrocytes from spontaneous or engineered germ-line mutant mice has been instrumental in characterizing the physiological functions of components of the red cell cytoskeleton and membrane. However, the red blood cell expresses some proteins whose germline loss-of-function is embryonic-lethal, perinatal-lethal, or confers reduced post-weaning viability. Promoter regions of erythroid-specific genes have been used to engineer erythroid-specific expression of Cre recombinase.

Purinergic signaling is essential for full Psickle activation by hypoxia and by normoxic acid pH in mature human sickle red cells and in vitro-differentiated cultured human sickle reticulocytes.

Paracrine ATP release by erythrocytes has been shown to regulate endothelial cell function via purinergic signaling, and this erythoid-endothelial signaling network is pathologically dysregulated in sickle cell disease. We tested the role of extracellular ATP-mediated purinergic signaling in the activation of Psickle, the mechanosensitive Ca-permeable cation channel of human sickle erythrocytes (SS RBC). Psickle activation increases intracellular [Ca] to stimulate activity of the RBC Gardos channel, KCNN4/KCa3.

Trpv1 and Trpa1 are not essential for Psickle-like activity in red cells of the SAD mouse model of sickle cell disease.

The molecular identity of Psickle, the deoxygenation-activated cation conductance of the human sickle erythrocyte, remains unknown. We observed in human sickle red cells that inhibitors of TRPA1 and TRPV1 inhibited Psickle, whereas a TRPV1 agonist activated a Psickle-like cation current. These observations prompted us to test the roles of TRPV1 and TRPA1 in Psickle in red cells of the SAD mouse model of sickle cell disease.

Evolution of Specimen Self-Collection in the COVID-19 Era: Implications for Population Health Management of Infectious Disease.

Laboratory testing is an important component in the diagnosis of respiratory tract infections such as with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, specimen collection not only risks exposure of health care workers and other patients to infection, but also necessitates use of personal protective equipment that may be in short supply during periods of heightened disease activity. Self-collection of nasal or oropharyngeal swabs offers an alternative to address these drawbacks.

Prophylaxis for thromboembolic disease and evaluation for thrombophilia.

Patients treated with total hip or knee arthroplasty are at risk for venous thromboembolic disease. Laboratory evaluation of thrombophilia can help to better identify patients at higher risk for venous thromboembolic disease, and newer methods that test for genetic factors continue to evolve; however, more research is needed to justify routine testing for thrombophilia. Research studies have yielded differing results in determining the most appropriate prophylactic regimen.

National assessment of warfarin anticoagulation therapy for stroke prevention in atrial fibrillation.

Background: Anticoagulation control with warfarin, as assessed by the international normalized ratio (INR), is challenging. Time in the therapeutic range has been inversely correlated with major hemorrhage, thrombosis, and mortality. Quest Diagnostics offers standardized INR laboratory testing services to approximately half of US physician practices.

Drug-induced lupus anticoagulants and antiphospholipid antibodies.

Lupus anticoagulants (LA) are immunoglobulins (IgG, IgM, and/or IgA) which interfere with one or more of phospholipid-dependent in vitro coagulation tests, eg, activated partial thromboplastin time (aPTT), kaolin clotting time (KCT), dilute Russell viper venom time (dRVVT), and dilute prothrombin time (dPT). LAs may be seen in a variety of clinical settings including the primary antiphospholipid syndrome (APS), systemic lupus erythematosus (SLE), other autoimmune diseases, secondary to infections, malignancies, and in association with certain drugs. LAs associated with the antiphospholipid syndrome and other autoimmune disease recognize certain phospholipid-binding proteins (β(2)-glycoprotein I [β(2)GPI] or prothrombin).

Asymptomatic factor VII deficiency: gene analysis and structure-function relationships.

Factor VII Padua is a variant form of factor VII deficiency characterized by a prolongation of the prothrombin time (PT), when the assay is performed using rabbit brain thromboplastin. The PT is normal when performed using either human or ox brain thromboplastin reagents, or a recombinant human tissue factor-based thromboplastin. We report a case of an African-American woman with asymptomatic factor VII deficiency, who had a prolonged PT and factor VII activity levels of 5-8% using rabbit brain thromboplastin, but a normal PT and factor VII activity levels when measured using recombinant human brain thromboplastin or tissue factor.

David B. Pall, PhD (1914-2004).

In this edition of the Pioneers and Pathfinders Series, the contributions of David B. Pall, PhD, to transfusion medicine are discussed. With the aid of Dr Pall's unpublished personal history and assistance from family members and the company he founded, we are able to provide perspective to several remarkable scientific advances.

Drug-induced thrombotic thrombocytopenic purpura/hemolytic uremic syndrome: a concise review.

An extensive variety of drugs have been associated with thrombotic thrombocytopenic purpura and hemolytic uremic syndrome (TTP/HUS). Although a direct causal effect has usually not been proven, the cumulative evidence linking several drugs with TTP/HUS is strong. This paper reviews several categories of drugs including antineoplastics, immunotherapeutics and anti-platelet agents that have been reported to induce TTP/HUS.

Thrombotic thrombocytopenic purpura: yesterday, today, tomorrow.

Although much has been learned about the pathophysiologic process of thrombotic thrombocytopenic purpura (TTP), both diagnostically and therapeutically, since its initial description by Moschcowitz in 1924, its etiology and treatments remain, in many instances, problematic. Thrombotic thrombocytopenic purpura remains a rare entity whose etiology is usually unknown, but several drugs and infections have now been implicated in its development (i.e.

Detection of genomic polymorphisms associated with venous thrombosis using the invader biplex assay.

A multi-site study to assess the accuracy and performance of the biplex Invader assay for genotyping five polymorphisms implicated in venous thrombosis was carried out in seven laboratories. Genotyping results obtained using the Invader biplex assay were compared to those obtained from a reference method, either allele-specific polymerase chain reaction (AS-PCR), restriction fragment length polymorphism (PCR-RFLP) or PCR-mass spectrometry. Results were compared for five loci associated with venous thrombosis: Factor V Leiden, Factor II (prothrombin) G20210A, methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, and plasminogen activator inhibitor (PAI-1) 4G/5G.