Biomedical subjects

Ian Forster

Publications and source records attributed to Ian Forster.

7 recordsLinked to original sources

PubMed2005

Recent advances in renal phosphate transport.

Phosphate (Pi) homeostasis is achieved by adjusting the intestinal absorption and the renal excretion. Renal proximal reabsorption of Pi is regulated by controlling the amount of NaPi-IIa cotransporters in the brush border membrane of proximal tubules. Therefore, the understanding of the molecular mechanisms that control the apical expression of NaPi-IIa is required to have a full picture of how phosphate balancing takes place. In this review we will summarize our present knowledge about the mechanisms involved in the regulation of the apical expression and membrane retrieval of this family of transporters.

Absorption↗

PubMed2005

Using the EDAC test to monitor abstinence and relapses during outpatient treatment.

The main objective of this study is to show the performance of the EDAC test in monitoring alcohol consumption during outpatient treatment. The EDAC is a new approach that uses routine laboratory tests to identify binge drinking as well as chronic drinking. The overall diagnostic performance of the EDAC fluctuates around 80 to 90% for both specificity and sensitivity. Close to two thousand subjects have been tested by the EDAC since the early eighties; 300 of these were patients undergoing treatment at different institutions across the U.S. This article selected five case studies to represent examples of classical drinking behaviors encountered in most outpatient clinics. The first four cases illustrate the use of the EDAC alone and the last case represents the use of the EDAC combined with CDT. These five case studies illustrate the use of the EDAC to detect relapse episodes, to monitor abstinence during outpatient treatment and to recognize a slip early enough to prevent more severe drinking. The use of biomarkers to monitor drinking behavior in alcohol dependent patients is gaining popularity because they provide objective information on a patient's drinking status when used as an adjunct to self-report.

Adult↗

PubMed2004

Aromatic amino acid transporter AAT-9 of Caenorhabditis elegans localizes to neurons and muscle cells.

The Caenorhabditis elegans genome encodes nine homologues of mammalian glycoprotein-associated amino acid transporters. Two of these C. elegans proteins (AAT-1 and AAT-3) have been shown to function as catalytic subunits (light chains) of heteromeric amino acid transporters. These proteins need to associate with a glycoprotein heavy chain subunit (ATG-2) to reach the cell surface in a manner similar to that of their mammalian homologues. AAT-1 and AAT-3 contain a cysteine residue in the second putative extracellular loop through which a disulfide bridge can form with a heavy chain. In contrast, six C. elegans members of this family (AAT-4 to AAT-9) lack such a cysteine residue. We show here that one of these transporter proteins, AAT-9, reaches the cell surface in Xenopus oocytes without an exogenous heavy chain and that it functions as an exchanger of aromatic amino acids. Two-electrode voltage clamp experiments demonstrate that AAT-9 displays a substrate-activated conductance. Immunofluorescence shows that it is expressed close to the pharyngeal bulbs within C. elegans neurons. The selective expression of an aat-9 promoter-green fluorescent protein construct in several neurons of this region and in wall muscle cells around the mouth supports and extends these localization data. Taken together, the results show that AAT-9 is expressed in excitable cells of the nematode head and pharynx in which it may provide a pathway for aromatic amino acid transport.

Amino Acid Transport Systems↗

PubMed2003

The sodium phosphate cotransporter family SLC34.

This review summarizes the characteristics of the solute carrier family SLC34 that is represented by the type ll Na/P(i)-cotransporters NaPi-lla (SLC34A1), NaPi-llb (SLC34A2) and NaPi-llc (SLC34A3). Other Na/P(i)-cotransporters are described within the SLC17 and SLC20 families. Type ll Na/P(i)-cotransporters are expressed in several tissues and play a major role in the homeostasis of inorganic phosphate. In kidney and small intestine, type ll Na/P(i)-cotransporters are located at the apical sites of epithelial cells and represent the rate limiting steps for transepithelial movement of phosphate. Physiological and pathophysiological regulation of renal and small intestinal epithelial transport of phosphate occurs through alterations in the abundance of type ll Na/P(i)-cotransporters.

Animals↗

PubMed2002

Potassium-selective atomic force microscopy on ion-releasing substrates and living cells.

A new method for simultaneous mapping of cell topography and ion fluxes was developed. A highly sensitive ion sensor system was generated by coating atomic force microscopy tips with a PVC layer containing valinomycin, an ionophore for potassium. The activity of specific ions was traced on artificial ion-releasing PVC substrates. A boundary potential was generated owing to the selective exchange of a specific ion between coated tip and ion-releasing substrate. The boundary potential was detectable as a force induced by ion-selective electrostatic interactions. The selectivity coefficient of valinomycin for potassium against sodium (K(K,Na)f) was -2.5 +/- 0.5. Potassium efflux was measured on living MDCK-F1 cells expressing BK(Ca) channels. We could demonstrate localized areas of high potassium concentrations at the cell surface. The potassium efflux could be reversibly inhibited by thapsigargin, which is known to inhibit the efflux of potassium from BK(Ca) channels by suppression of calcium ATPase.

Biosensing Techniques↗

PubMed2002

Regulation of Na/Pi transporter in the proximal tubule.

The physiological tuning and pathophysiological alterations of renal proximal reabsorption of inorganic phosphate can be ascribed to the net amount of the Na/Pi-cotransporter NaPi-IIa localized in the brush border membrane. The net amount of NaPi-IIa appears to be the result of an endocytotic rate regulated by a complex network of different protein kinases. New approaches demonstrated that NaPi-IIa is part of heteromeric protein complexes, organized by PDZ (postsynaptic protein PSD95, Drosophila junction protein Disc-large, tight junction protein ZO-1) proteins. Such complexes are thought to play important roles in the apical positioning and regulated endocytosis of NaPi-IIa and therefore such interactions have to be considered when explaining proximal phosphate ion reabsorption.

Animals↗

PubMed2002

The renal type IIa Na/Pi cotransporter: structure-function relationships.

The type IIa Na/Pi cotransporter mediates proximal tubular brush-border membrane secondary active phosphate (Pi) flux. It is rate limiting in tubular Pi reabsorption and, thus, a final target in many physiological and pathophysiological situations of altered renal Pi handling. In the present short review, we will briefly summarize our current knowledge about the transport mechanism (cycle) as well as particular regions of the transporter protein ("molecular domains") that potentially determine transport characteristics.

Amino Acid Sequence↗