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R G Wells

Publications and source records attributed to R G Wells.

At least 37 records · Page 2Linked to original sources
PubMed1994

The high affinity Na+/glucose cotransporter. Re-evaluation of function and distribution of expression.

We report the primary structure, functional characterization, and tissue distribution of the high affinity Na+/glucose cotransporter SGLT1 from rat kidney. Rat SGLT1 (665 amino acid residues) is 86-87% identical to SGLT1 from rabbit, pig, and human. High stringency Northern analysis demonstrated that SGLT1 is strongly expressed in small intestine and at lower levels in kidney, liver, and lung. In situ hybridization performed on kidney sections revealed that SGLT1 is predominantly present in S3 segments of the proximal tubule. In small intestine, SGLT1 message was located in cells of the lower two-thirds of intestinal villi. Expression of rat SGLT1 in Xenopus oocytes resulted in a large Na(+)-dependent uptake of [14C]-alpha-methyl-D-glucopyranoside (alpha MeGlc). Overall, the transport characteristics were similar to those of rabbit SGLT1. High affinity Na+/glucose cotransport in membrane vesicles was previously shown to be coupled to the cotransport of two Na+ ions (Turner, R. J., and Moran, A. (1982) J. Membr. Biol. 70, 37-45). Previous kinetic analysis of rat and rabbit SGLT1, however, demonstrated between second and first order dependence of sugar uptake on extracellular Na+ concentration, suggesting the existence of Na(+)-binding sites with different affinities. Here, we directly compared the initial rates of the alpha MeGlc uptake with alpha MeGlc-induced inward currents as an indicator of the Na+ flux. This analysis clearly revealed a Na+ to glucose coupling ratio of 2:1. In summary, our data provide important insights into the function and tissue distribution of the high affinity Na+/glucose cotransporter SGLT1 and clarify its role in the reabsorption mechanism of D-glucose in the kidney.

Amino Acid Sequence↗
PubMed1994

AIDS: sonography of hyperechoic renal pyramids in renal candidiasis.

A 13-month-old patient with autoimmune deficiency syndrome had renal candidiasis. An abnormal renal sonographic pattern of hyperechoic renal pyramids was demonstrated. This abnormal sonographic finding should suggest renal candidiasis in an immune suppressed child. In the normal kidney of children, the pyramids are hypoechoic. This pattern has not been noted in previous publications. We report this case.

AIDS-Associated Nephropathy↗
PubMed1994

Adrenal hyperechogenicity in hemolytic uremic syndrome.

Hemolytic uremic syndrome is characterized by an abrupt onset of a microangiopathy, thrombocytopenia, hemolytic anemia and renal failure. These abnormalities present in varying degrees. The vascular abnormalities include endothelial swelling and thrombus formation. The kidney is the major target of involvement, although intestines, lung and brain may also be affected. It is considered a disease of the infant, although it occurs in older children and adults as a component of thrombotic thrombocytopenic purpura. We present the sonographic findings of adrenal involvement in a child with hemolytic uremic syndrome, which seems to be a rare occurrence. The patient developed adrenal insufficiency during the acute phase of the disease.

Adrenal Glands↗
PubMed1993

Localization of the Na+/glucose cotransporter gene SGLT2 to human chromosome 16 close to the centromere.

The chromosomal location of the gene SGLT2, which is presumed to encode a low-affinity Na+/glucose cotransporter, has been determined using a panel of rodent-human somatic cell hybrids. Southern blot analysis of genomic DNA from 16 different hybrids shows that SGLT2 is located on chromosome 16. Analysis of three additional hybrids that selectively retain all or part of human chromosome 16 demonstrates that SGLT2 is located close to the centromere in band p11.2 of the chromosome.

Animals↗
PubMed1993

Spine pain in children.

Spine pain in children as an isolated symptom is infrequently seen in clinical practice. However, as opposed to spine pain in adults, it is accompanied by a relatively higher frequency of pathology. Diagnostic imaging is a necessary follow up to the physical examination and laboratory studies. Standard radiography is usually the initial imaging study. Frequently, however, additional imaging with bone scintigraphy, computed tomography, or magnetic resonance imaging is necessary to add sensitivity and specificity to the clinical presentation. We describe the disease entities, pathophysiology, and imaging characteristics of the varied pathologies responsible for spine pain in children.

Adolescent↗
PubMed1993

Cloning and chromosomal localization of a human kidney cDNA involved in cystine, dibasic, and neutral amino acid transport.

We have recently cloned, sequenced, and characterized a rat kidney cDNA (D2) that stimulates cystine as well as dibasic and neutral amino acid transport. In order to evaluate the role of this protein in human inherited diseases such as cystinuria, we have isolated a human D2 clone (D2H) by low stringency screening of a human kidney cDNA library using the radiolabeled D2 insert as a probe. The D2H cDNA is 2284 nucleotides long and encodes a 663 amino acid protein that is 80% identical to the rat D2 amino acid sequence and 86% to that of the rabbit homologue rBAT. Microinjection of in vitro transcribed D2H cRNA into Xenopus oocytes induced uptake of cystine as well as dibasic and neutral amino acids in a pattern similar to that of rat D2 and rabbit rBAT. Both neutral and dibasic amino acids inhibited the D2H-induced uptake of cystine. Northern blot analysis demonstrated that D2H, like D2 and rBAT, is expressed strongly in the kidney and intestine. Southern blot analysis of genomic DNA from a panel of mouse-human somatic cell hybrids showed that the human gene for D2H resides on chromosome 2.

Amino Acid Sequence↗
PubMed1992

The 4F2 antigen heavy chain induces uptake of neutral and dibasic amino acids in Xenopus oocytes.

The 4F2 cell surface antigen is a disulfide-linked heterodimer induced during the process of cellular activation and expressed widely in mammalian tissues (Parmacek, M. S., Karpinski, B. A., Gottesdiener, K. M., Thompson, C. B., and Leiden, J. M. (1989) Nucleic Acids Res. 17, 1915-1931). The human heavy chain component, a type II membrane glycoprotein, has 29% identity to the amino acid transport-related protein encoded by the recently cloned rat D2 cDNA. We have demonstrated that Xenopus oocytes injected with in vitro transcribed cRNA from D2 take up cystine and dibasic and neutral amino acids (Wells, R. G., and Hediger, M. A. (1992) Proc. Natl. Acad. Sci. U. S. A. 89, 5596-5600). In the present study, we examine the role of the human 4F2 heavy chain in amino acid transport. In vitro transcribed 4F2 cRNA was injected into Xenopus oocytes which were assayed for the uptake of radiolabeled amino acids. Our results show that cRNA from 4F2 stimulates the uptake of dibasic and neutral amino acids into oocytes at levels up to 3-fold higher than for water-injected control oocytes. There is no demonstrable uptake of cystine. Uptake is saturable, with characteristics of high affinity transport, and inhibition data suggest that uptake occurs via a single transporter. Dibasic amino acids are taken up by both 4F2 and D2 cRNA-injected oocytes in a sodium-independent manner. In contrast, 4F2-induced but not D2-induced neutral amino acid uptake has a significant component of sodium dependence. Likewise, neutral amino acids in excess inhibit the 4F2-induced uptake of radiolabeled arginine but not leucine in a sodium-dependent manner. The 4F2-induced uptake we observe most likely represents the activity of a single transport system with some characteristics of systems y+, b0,+, and B0,+. We suggest that 4F2 and D2 represent a new family of proteins which induce amino acid transport with distinct characteristics, possibly functioning as transport activators or regulators.

Amino Acids↗
PubMed1992

Cloning of a rat kidney cDNA that stimulates dibasic and neutral amino acid transport and has sequence similarity to glucosidases.

The transport of amino acids across cell membranes is believed to be mediated by integral membrane proteins with distinct substrate specificities. Using expression cloning in Xenopus oocytes and assaying for the uptake of 14C-labeled cystine, we isolated a 2.3-kilobase cDNA (D2) from a rat kidney library. D2 is expressed specifically in kidney and intestine and induces the transport of both neutral and cationic amino acids. The deduced amino acid sequence predicts a 78-kDa protein with a single transmembrane domain, a structure not typical of the known membrane transport proteins, which generally have multiple membrane-spanning regions. The putative extracellular region is highly similar to the 4F2 heavy-chain cell surface antigen and to a family of alpha-glucosidases, which raises the possibility that D2 encodes a transport activator or regulatory subunit.

Amino Acid Sequence↗