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Biomedical subjects

J M Symons

Publications and source records attributed to J M Symons.

7 recordsLinked to original sources

Integrins in kidney development, function, and disease.

Integrins are heterodimeric cell surface receptors that mediate heterophilic cell-cell interactions and interactions between cells and the extracellular matrix (Hynes RO. Cell 69: 11-25, 1991). As such, they are involved in morphogenetic processes during development, as well as in the maintenance of normal tissue architecture in fully developed organs. Integrins are now recognized to be a large family of receptors, and several different integrins have been demonstrated as being expressed in the developing and adult kidney (Korhonen M, Ylkanne J, Laitinen L, and Virtanen I. Development 122: 3537-3547, 1996; Rahilly MA and Fleming S. J Pathol 167: 327-334, 1992). This review will summarize present knowledge about integrin expression in the developing, normal, and diseased kidney and attempt to provide a hypothetical framework for understanding integrin function in the urogenital system. Since the last time this area was reviewed (Hamerski DA and Santoro S. Curr Opin Nephrol Hypertens 8: 9-14, 1999), there have been significant publications on the roles of integrins in kidney development and disease. At present, there are many more questions than answers, and integrins present an area where many novel and exciting findings will emerge in the coming years.

Aging↗

Mycophenolate mofetil in pediatric renal transplantation.

The use of mycophenolate mofetil (MMF) in adult renal transplantation has been associated with significantly decreased incidence of acute rejection. However, limited data are available for children after renal transplantation. A total of 67 patients undergoing renal transplantation at the University of Alabama at Birmingham, AL, USA and Children's Hospital of Boston, MA, USA were enrolled into the Cooperative Clinical Trials in Pediatric Transplantation randomized controlled trial of induction with OKT3 vs. i.v. cyclosporin A (CsA) at the time of transplantation. The first 31 patients entered were begun on azathioprine (AZA), 2 mg/kg on the first post-operative day. The subsequent 36 patients were begun on MMF, 1000 mg/m2/d. Other maintenance immunosuppression included oral CsA and Prednisone. Biopsy confirmation was obtained for all suspected rejection episodes. Glomerular filtration rate (GFR) was calculated using the Schwartz formula. Data were analyzed using Kaplan Meier survival curves and compared using log-rank tests. At the time of analysis, 52 patients (mean age 10.1 +/- 5 yr) had completed at least 12 months and 15 others had completed at least 6 months of follow-up post-transplantation. Of these, there were 39 male/28 female; 48 white/15 black/4 other; 49 living donor/18 cadaver donor. There were no significant differences in the incidence of rejection episodes, number of rejection episodes, the GFR at 6 and 12 months, allograft, or patient survival between patients receiving MMF vs. AZA. We could demonstrate no significant differences in these outcomes based on sex, race or induction therapy, leading to the conclusion that pediatric patients treated under a consistent protocol in two institutions have no improvement in short-term allograft outcome with the addition of MMF therapy.

Adolescent↗

(Alpha)3(beta)1 integrin regulates epithelial cytoskeletal organization.

Epithelial cell morphology and cytoskeletal organization are determined by interactions, with both adjacent cells and the extracellular matrix, which are mediated by integrins and cadherins. Little is known, however, of the relative contributions of integrins and cadherins to maintaining the sub-cortical cytoskeleton characteristic of epithelial cells. Since most studies that utilize integrin-blocking antibodies result in a loss of both cell-cell adhesion and sub-cortical cytoskeletal organization, it has been difficult to distinguish whether integrins and cadherins both mediate cytoskeletal assembly in epithelial cells. Therefore, cells derived from kidney collecting ducts of (alpha)3(beta)1 integrin-deficient mice were used to examine the role of integrins in epithelial cell morphology and cytoskeletal organization. In primary cell culture, (alpha)3(beta)1 integrin-deficient kidney collecting duct cells maintain cadherin-mediated cell-cell adhesions but fail to form the sub-cortical cytoskeleton that is characteristic of epithelial cells, and instead assemble actin stress fibers. Moreover, the cell-cell junctions in mutant cells were irregular, rather than being uniformly oriented perpendicular to the culture substrate. These results demonstrated that integrins have an primary and essential function in establishing and maintaining the sub-cortical cytoskeleton that is characteristic of epithelial cells. To further study the role of (alpha)3(beta)1 integrin in establishing and maintaining cytoskeletal organization in tubular epithelial cells, we derived immortalized cell lines from wild-type and (alpha)3(beta)1 integrin-deficient kidney collecting ducts that duplicated the cytoskeletal and cadherin organization observed in primary cells. E-cadherin and (alpha)- and (beta)-catenin were complexed together in equal amounts in membranes of wild-type and (alpha)3(beta)1 integrin-deficient cells. However, association of the cadherin:catenin complex with (alpha)-actinin was greatly decreased in mutant cells, indicating that integrin-mediated assembly of the sub-cortical cytoskeleton is essential for subsequent association of the cytoskeleton with the cadherin:catenin complex. These results present direct evidence for integrin:cadherin cross-regulation in which cadherin function is dependent on the presence of an integrin.

Animals↗

An advanced oxidation process for DBP control.

Small water utilities often have difficulty operating complicated treatment processes. The advanced oxidation process investigated here is simple, involving only a pump to add hydrogen peroxide and a power supply for the ultraviolet lamps, and the process does not produce any solid residuals. The results of these studies show that a photon-flux-driven pseudo-first-order model (known as the Prengle-Shimoda rate model) could be used to predict the destruction of total organic carbon, dissolved organic halogen, and dissolved organic halogen precursors.

Benzene↗

Technical note: interference of Br-, BrO3-, and ClO3- with DOX determination.

In the dissolved organic halogen (DOX) analytic test, prior to combustion, the granular activated carbon (GAC) on which the DOX is absorbed is washed with a sodium nitrate solution designed to remove any inorganic chloride that may have also adsorbed to the GAC. Thus, a potential positive interference is removed. This study investigated the effectiveness of the nitrate wash in eliminating possible interferences from bromide, bromate, and chlorate ions. No interference was detected from bromate or chlorate ion, but a small positive interference of about 12 micrograms Cl-/L per mg/L of bromide ion was found in the presence of background organic matter.

Bromates↗

Using anion exchange resins to remove THM precursors.

This study investigated the control of trihalomethanes (THMs) with ion exchange by comparing the THM formation potentials of the organic fractions in the influent to three column systems. The results showed that the smallest organic fraction, <0.5 K apparent molecular weight (AMW), was most reactive with free available chlorine. With the ion exchange system, the 1--5K-, 0.5K--1K-, and < 0.5-AMW organic fractions produced the majority of THMs, whereas with the granular activated carbon (GAC) and the combined ion exchange-GAC systems, the <0.5-AMW fraction produced most of the THMs. The authors conclude that regeneration of the resin of the ion exchange column at sulfate breakthrough, in combination with a GAC column, will produce a water very low in THM formation potential.

Anion Exchange Resins↗