The 'Insertion/Deletion' Polymorphism, rs4340 and Diabetes Risk: A Pilot Study from a Hospital Cohort.

The insertion/deletion, I/D polymorphism, in the gene encoding Angiotensin Converting Enzyme, ACE is a popular genetic marker for cardiovascular disease, CVD. With alarming rise in diabetes, the risk of CVD among Indian subjects is further enhanced. The present study explored the role of ACE I/D polymorphism, rs4340 as a genetic marker and its association with diabetes.

Archaeomagnetic results from Cambodia in Southeast Asia: Evidence for possible low-latitude flux expulsion.

Extensive spatial and temporal distribution of high-quality data are essential for understanding regional and global behaviors of the geomagnetic field. We carried out chronological and archaeomagnetic studies at the Angkor-era iron-smelting site of Tonle Bak in Cambodia in Southeast Asia, an area with no data available to date. We recovered high-fidelity full-vector geomagnetic information from the 11th to 14th century for this region, which fill gaps in the global distribution of data and will significantly improve the global models.

The Association of Fever and Antipyretic Medication With Outcomes in Mechanically Ventilated Patients: A Cohort Study.

Background: Fever is common in mechanically ventilated patients and may be uniquely detrimental in those with lung injury because of its injurious effects on pulmonary vascular permeability and alveolar epithelium. We evaluated the association of fever and antipyretic medication with mortality in mechanically ventilated emergency department (ED) patients.

Methods: This is a retrospective cohort study of 1,264 patients requiring mechanical ventilation initiated in the ED with subsequent admission to an intensive care unit.

Red blood cell phenotype fidelity following glycerol cryopreservation optimized for research purposes.

Intact red blood cells (RBCs) are required for phenotypic analyses. In order to allow separation (time and location) between subject encounter and sample analysis, we developed a research-specific RBC cryopreservation protocol and assessed its impact on data fidelity for key biochemical and physiological assays. RBCs drawn from healthy volunteers were aliquotted for immediate analysis or following glycerol-based cryopreservation, thawing, and deglycerolization.

An mTOR anti-sense oligonucleotide decreases polycystic kidney disease in mice with a targeted mutation in Pkd2.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common life-threatening hereditary disease in the USA. In human ADPKD studies, sirolimus, a mammalian target of rapamycin complex 1 (mTORC1) inhibitor, had little therapeutic effect. While sirolimus robustly inhibits mTORC1, it has a minimal effect on mTOR complex 2 (mTORC2).

Human podocytes perform polarized, caveolae-dependent albumin endocytosis.

The renal glomerulus forms a selective filtration barrier that allows the passage of water, ions, and small solutes into the urinary space while restricting the passage of cells and macromolecules. The three layers of the glomerular filtration barrier include the vascular endothelium, glomerular basement membrane (GBM), and podocyte epithelium. Podocytes are capable of internalizing albumin and are hypothesized to clear proteins that traverse the GBM.

Achieving the Great Lakes Initiative mercury limits in oil refinery effluent.

To meet the stringent Great Lakes Initiative (GLI) wastewater discharge mercury (Hg) limit of 1.3 ppt (ng/L), mercury removal technologies need to be identified and investigated. The goals of this study were to (1) identify and assess available wastewater treatment technologies for mercury removal from an oil refinery wastewater; and (2) conduct bench-scale tests to provide comparable, transparent, and uniform results to assess their performance at low mercury concentrations.

Shank2 contributes to the apical retention and intracellular redistribution of NaPiIIa in OK cells.

In renal proximal tubule (PT) cells, sodium-phosphate cotransporter IIa (NaPiIIa) is normally concentrated within the apical membrane where it reabsorbs ∼70% of luminal phosphate (Pi). NaPiIIa activity is acutely regulated by moderating its abundance within the apical membrane. Under low-Pi conditions, NaPiIIa is retained within the apical membrane.

NHE3 regulatory factor 1 (NHERF1) modulates intestinal sodium-dependent phosphate transporter (NaPi-2b) expression in apical microvilli.

P(i) uptake in the small intestine occurs predominantly through the NaPi-2b (SLC34a2) co-transporter. NaPi-2b is regulated by changes in dietary P(i) but the mechanisms underlying this regulation are largely undetermined. Sequence analyses show NaPi-2b has a PDZ binding motif at its C terminus.

Shank2 redistributes with NaPilla during regulated endocytosis.

Serum phosphate levels are acutely impacted by the abundance of sodium-phosphate cotransporter IIa (NaPiIIa) in the apical membrane of renal proximal tubule cells. PSD-95/Disks Large/Zonula Occludens (PDZ) domain-containing proteins bind NaPiIIa and likely contribute to the delivery, retention, recovery, and trafficking of NaPiIIa. Shank2 is a distinctive PDZ domain protein that binds NaPiIIa.

Sirolimus attenuates disease progression in an orthologous mouse model of human autosomal dominant polycystic kidney disease.

In autosomal dominant polycystic kidney disease (ADPKD), abnormal proliferation of tubular cells drives cyst development and growth. Sirolimus, an inhibitor of the protein kinase mammalian target of rapamycin (mTOR) and a potent anti-proliferative agent, decreases cyst growth in several genetically distinct rodent models of polycystic kidney disease (PKD). We determined here the effect of sirolimus on renal cyst growth in Pkd2WS25/- mice; an ortholog of human ADPKD involving mutation of the Pkd2 gene.

Distinct patterns of kidney and liver cyst growth in pkd2(WS25/-) mice.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disease that results in the development of cystic kidneys and liver. Pkd2(WS25/-) mice are a key genetic mouse model of human ADPKD that recapitulate the 'molecular recessive' nature of human ADPKD. Providing the foundation for future long-term studies, the present work documents distinct patterns of long-term cyst growth in the kidneys and liver of male and female pkd2(WS25/-) mice.

Liver cyst cytokines promote endothelial cell proliferation and development.

Autosomal dominant polycystic kidney (ADPKD) is highly prevalent genetic disease. Liver cyst disease is the most common extrarenal manifestation in ADPKD and accounts for up to 10% of ADPKD morbidity and mortality. The clinical features of ADPKD liver disease arise from dramatic increases in liver cyst volumes.

Extracellular nucleotides stimulate Cl- currents in biliary epithelia through receptor-mediated IP3 and Ca2+ release.

Extracellular ATP regulates bile formation by binding to P2 receptors on cholangiocytes and stimulating transepithelial Cl(-) secretion. However, the specific signaling pathways linking receptor binding to Cl(-) channel activation are not known. Consequently, the aim of these studies in human Mz-Cha-1 biliary cells and normal rat cholangiocyte monolayers was to assess the intracellular pathways responsible for ATP-stimulated increases in intracellular Ca(2+) concentration ([Ca(2+)](i)) and membrane Cl(-) permeability.

CXCR2 agonists in ADPKD liver cyst fluids promote cell proliferation.

Autosomal dominant polycystic kidney disease (ADPKD) is a highly prevalent genetic disease that results in cyst formation in kidney and liver. Cytokines and growth factors secreted by the cyst-lining epithelia are positioned to initiate autocrine/paracrine signaling and promote cyst growth. Comparative analyses of human kidney and liver cyst fluids revealed disparate cytokine/growth factor profiles.

Characterization of ionotrophic purinergic receptors in hepatocytes.

Unlabelled: Ionotrophic purinergic (P2X) receptors function as receptor-gated cation channels, where agonist binding leads to opening of a nonselective cation pore permeable to both Na(+) and Ca(2+). Based on evidence that extracellular adenosine 5'-triphosphate (ATP) stimulates glucose release from liver, these studies evaluate whether P2X receptors are expressed by hepatocytes and contribute to ATP-dependent calcium signaling and glucose release. Studies were performed in isolated hepatocytes from rats and mice and hepatoma cells from humans and rats.

Polycystic liver: clinical characteristics of patients with isolated polycystic liver disease compared with patients with polycystic liver and autosomal dominant polycystic kidney disease.

Aim: The goal of this study was to compare the clinical features of patients with isolated polycystic liver disease (PCLD) with those of patients with polycystic liver and autosomal dominant polycystic kidney disease (ADPKD).

Methods: Cases were identified from clinical records at the University of Colorado Hospital in Denver (USA) and at the Radboud University Hospital in Nijmegen (the Netherlands) by ICD-10 codes. To be included in this analysis, patients had to have an initial diagnosis of PCLD within six years of presentation to our clinics.

VEGF receptor inhibition blocks liver cyst growth in pkd2(WS25/-) mice.

Proliferation of cyst-lining epithelial cells is an integral part of autosomal dominant polycystic kidney disease (ADPKD) cyst growth. Cytokines and growth factors within cyst fluids are positioned to induce cyst growth. Vascular endothelial growth factor (VEGF) is a pleiotropic growth factor present in ADPKD liver cyst fluids (human 1,128 +/- 78, mouse 2,787 +/- 136 pg/ml) and, to a lesser extent, in ADPKD renal cyst fluids (human 294 +/- 41, mouse 191 +/- 90 pg/ml).

Regulated ion transport in mouse liver cyst epithelial cells.

Derived from bile duct epithelia (BDE), secretion by liver cyst-lining epithelia is positioned to drive cyst expansion but the responsible ion flux pathways have not been characterized. Cyst-lining epithelia were isolated and cultured into high resistance monolayers to assess the ion secretory pathways. Electrophysiologic studies showed a marked rate of constitutive transepithelial ion transport, including Cl(-) secretion and Na(+) absorption.

Bicarbonate-rich choleresis induced by secretin in normal rat is taurocholate-dependent and involves AE2 anion exchanger.

Canalicular bile is modified along bile ducts through reabsorptive and secretory processes regulated by nerves, bile salts, and hormones such as secretin. Secretin stimulates ductular cystic fibrosis transmembrane conductance regulator (CFTR)-dependent Cl- efflux and subsequent biliary HCO3- secretion, possibly via Cl-/HCO3- anion exchange (AE). However, the contribution of secretin to bile regulation in the normal rat, the significance of choleretic bile salts in secretin effects, and the role of Cl-/HCO3- exchange in secretin-stimulated HCO3- secretion all remain unclear.

Shank2 associates with and regulates Na+/H+ exchanger 3.

Na+/H+ exchanger 3 (NHE3) plays a pivotal role in transepithelial Na+ and HCO3(-) absorption across a wide range of epithelia in the digestive and renal-genitourinary systems. Accumulating evidence suggests that PDZ-based adaptor proteins play an important role in regulating the trafficking and activity of NHE3. A search for NHE3-binding modular proteins using yeast two-hybrid assays led us to the PDZ-based adaptor Shank2.

Shank2E binds NaP(i) cotransporter at the apical membrane of proximal tubule cells.

Proteins expressing postsynaptic density (PSD)-95/Drosophila disk large (Dlg)/zonula occludens-1 (ZO-1) (PDZ) domains are commonly involved in moderating receptor, channel, and transporter activities at the plasma membrane in a variety of cell types. At the apical membrane of renal proximal tubules (PT), the type IIa NaP(i) cotransporter (NaP(i)-IIa) binds specific PDZ domain proteins. Shank2E is a spliceoform of a family of PDZ proteins that is concentrated at the apical domain of liver and pancreatic epithelial cell types and is expressed in kidney.

Increased susceptibility of fat-laden Zucker-rat hepatocytes to bile acid-induced oncotic necrosis: an in vitro model of steatocholestasis.

Unlabelled: Metabolic liver disorders cause chronic liver disease and liver failure in childhood. Many of these disorders share the histologic features of steatosis and cholestasis, or steatocholestasis. In this study we sought to (1) develop an in vitro model of steatocholestasis, (2) determine the mechanisms of cell death in this model, and (3) determine the role of mitochondrial disturbances in this model.

Protein kinase C regulates the phosphorylation and oligomerization of ERM binding phosphoprotein 50.

Ezrin-Radixin-Moesin (ERM) binding phosphoprotein 50 (EBP50, a.k.a.