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David W Ploth

Publications and source records attributed to David W Ploth.

9 recordsLinked to original sources

Cloning and functional characterization of a second urea transporter from the kidney of the Atlantic stingray, Dasyatis sabina.

The cloning of cDNAs encoding facilitated urea transporters (UTs) from the kidneys of the elasmobranchs indicates that in these fish renal urea reabsorption occurs, at least in part, by passive processes. The previously described elasmobranch urea transporter clones from shark (shUT) and stingray (strUT-1) differ from each other primarily because of the COOH-terminus of the predicted strUT-1 translation product being extended by 51-amino acid residues compared with shUT. Previously, we noted multiple UT transcripts were present in stingray kidney. We hypothesized that a COOH terminally abbreviated UT isoform, homologous to shUT, would also be present in stingray kidney. Therefore, we used 5'/3' rapid amplification of cDNA ends to identify a 3'UTR-variant (strUT-1a) of the cDNA that encodes (strUT-1), as well as three, 3'UTR-variant cDNAs (strUT-2a,b,c) that encode a second phloretin-sensitive, urea transporter (strUT-2). The 5'UTR and the first 1,132 nucleotides of the predicted coding region of the strUT-2 cDNAs are identical to the strUT-1 cDNAs. The remainder of the coding region contains only five novel nucleotides. The strUT-2 cDNAs putatively encode a 379-amino acid protein, the first 377 amino acids identical to strUT-1 plus 2 additional amino acids. We conclude that 1) a second UT isoform is expressed in the Atlantic stingray and that this isoform is similar in size to the UT previously cloned from the kidney of the dogfish shark, and 2) at least five transcripts encoding the 2 stingray UTs are derived from a single gene product through alternative splicing and polyadenylation.

Amino Acid Sequence↗

Effect of low environmental salinity on plasma composition and renal function of the Atlantic stingray, a euryhaline elasmobranch.

Marine elasmobranchs maintain internal osmolality higher than their external environment, resulting in an osmotic gradient for branchial water uptake. This gradient is markedly increased in low-salinity habitats. The subsequent increase in water uptake presents a challenge to volume homeostasis. The Atlantic stingray is a marine elasmobranch that inhabits a remarkable range of environmental salinities. We hypothesized that the ability of these stingrays to regulate fluid volume in low-salinity environments is due primarily to a renal glomerular and tubular functional reserve. We tested this hypothesis by measuring renal excretory function after a rapid and sustained 50% reduction in the osmolality of the external medium. Atlantic stingrays were maintained in harbor water [control salinity (CS) approximately 850 mosmol/kgH(2)O] for 1 wk. Rays were then either transferred to diluted harbor water [low salinity (LS) approximately 440 mosmol/kgH(2)O] or maintained in CS for a further 24 h. Renal excretory function was markedly higher in the rays subjected to low salinity. Glomerular filtration rate was threefold higher and urine flow rate ninefold higher in the LS group. The clearance of solute-free water was greater, and solute-free water comprised a significantly larger proportion of the urine output for the stingrays transferred to dilute harbor water. We conclude that 1) the kidneys of Atlantic stingrays have a remarkable glomerular and tubular functional reserve, and 2) the marked increase in renal function attenuates the increase in fluid volume when these fish move into low-salinity habitats.

Acclimatization↗

Prospective analysis of global costs for maintenance of patients with ESRD.

BACKGROUND: The prevalence of end-stage renal disease (ESRD) has doubled in the past decade, with total costs projected to exceed 16.5 billion dollars by the end of 2002. METHODS: The purpose of this prospective study is to determine all costs related to inpatient and outpatient health care utilization incurred by 76 patients with ESRD in an outpatient hemodialysis setting for 1 year. Costs were derived from a computer-based cost-allocation process that distributed cost components and overhead to designated revenue-producing departments. RESULTS: During the 1-year study period, these patients had 1,459 total inpatient and outpatient hospital visits (mean, 19.2 visits/patient; range, 0 to 84 visits/patient). There were 149 general inpatient hospital admissions. Of 238 total emergency room visits, 89 visits resulted in admission to the hospital (37%). CONCLUSION: Total hospital costs for all patients for the year were 1,831,880 dollars (actual charges, 2,929,147 dollars). As expected, the greatest hospital cost expenditures were attributed to inpatient hospital admissions (1,419,022 dollars; 77.5% of total). Of total hospital costs, inpatient bed costs were the single highest expenditure. The cost for outpatient hemodialysis therapy was 33,784 dollars/patient-year, consisting of facility costs of 17,200 dollars, outpatient pharmacy costs of 14,100 dollars, and outpatient professional costs of 2,500 dollars/patient-year. Average costs for hospital facility and/or professional fees were 42,730 dollars/patient-year, whereas average costs for outpatient dialysis facility and/or professional fees were 33,784 dollars, for an estimated global cost of 76,515 dollars/patient-year. Our cost estimate for care of this unique inner-city population substantially exceeds those reported earlier by others.

Academic Medical Centers↗

Hyponatremia associated with 3,4-methylenedioxymethylamphetamine ("Ecstasy") abuse.

We present a case of acute, symptomatic hyponatremia in a young woman that developed after use of 3,4-methylenedioxymethylamphetamine (MDMA), more commonly known as "ecstasy." The patient was treated with 5% saline and had complete recovery. The pathogenesis of MDMA-associated hyponatremia involves excessive water intake and inappropriately elevated antidiuretic hormone (ADH) levels. It seems that young, premenopausal women are at particularly high risk for the development of severe, symptomatic hyponatremia after use of this drug. Review of the literature revealed 4 fatal outcomes from MDMA-associated hyponatremia. All were women and all died from cerebellar tonsillar herniation. We suggest that acute hyponatremia that develops after MDMA use may be a life-threatening condition. Recent recommendation that MDMA users should drink large volumes of water may not be appropriate.

Adolescent↗

Molecular and functional characterization of a urea transporter from the kidney of the Atlantic stingray.

In general, marine elasmobranch fishes (sharks, skates, and rays) maintain body fluid osmolality above seawater, principally by retaining large amounts of urea. Maintenance of the high urea concentration is due in large part to efficient renal urea reabsorption. Regulation of renal urea reabsorption also appears to play a role in maintenance of fluid homeostasis of elasmobranchs that move between habitats of different salinities. We identified and cloned a novel 2.7-kb cDNA from the kidney of the euryhaline Atlantic stingray Dasyatis sabina (GenBank accession no. AF443781). This cDNA putatively encoded a 431-amino acid protein (strUT-1) that had a high degree of sequence identity (71%) to the shark kidney facilitated urea transporter (UT). However, the predicted COOH-terminal region of strUT-1 appears to contain an additional sequence that is unique among cloned renal UTs. Injection of strUT-1 cRNA into Xenopus oocytes induced a 33-fold increase in [(14)C]urea uptake that was inhibited by phloretin. Four mRNA bands were detected in kidney by Northern blot: a transcript at 2.8 kb corresponding to the expected size of strUT-1 mRNA and bands at 3.8, 4.5, and 5.5 kb. Identification of a facilitated UT in the kidney of the Atlantic stingray provides further support for the proposal that passive mechanisms contribute to urea reabsorption by elasmobranch kidney.

Amino Acid Sequence↗

Renal transplant in patients with Alport's syndrome.

We evaluated 52 renal grafts transplanted into 41 patients with a pretransplantation diagnosis of Alport's syndrome. Overall 1-, 5-, and 10-year patient and graft survival rates were 95.1%, 90.2%, and 80.5% and 86.8%, 66%, and 45.3%, respectively. Although 14% of renal graft biopsy specimens examined with immunofluorescent microscopy showed linear glomerular basement membrane (GBM) immunoglobulin G deposits, only 1 of 41 patients (2.4%) or 52 grafts (1.9%) developed posttransplantation anti-GBM disease. The incidence of anti-GBM disease was 3.1% (1 of 32 patients) in a subgroup of male transplant recipients. Our analysis suggests that the incidence of anti-GBM disease in transplant recipients with Alport's syndrome is less than previously reported. In addition, it does not appear that HLA-DR alleles, which predispose to the development of anti-GBM disease in native kidneys, have a role in transplant recipients with Alport's syndrome posttransplantation. However, immunosuppression level may have a pathophysiological role in the development of anti-GBM disease. The majority of grafts in transplant recipients with Alport's syndrome failed because of chronic allograft nephropathy (69% of grafts) and acute rejection (22% of grafts). A history of previous acute rejection was the only factor that significantly affected graft outcome.

Anti-Glomerular Basement Membrane Disease↗

Molecular and functional characterization of a urea transporter from the kidney of a short-finned pilot whale.

Cetaceans (whales and dolphins) always excrete urine with an osmolality markedly higher than that of plasma. Although the mechanisms by which cetaceans concentrate urine have not been elucidated, data support a role for medullary urea accumulation in this process, as is the case for terrestrial mammals. Therefore, we hypothesized that facilitated urea transporters are present in the kidney of cetaceans. Using 5'/3'-rapid amplification of cDNA ends, we cloned a 2.7-kb cDNA from the kidney of the short-finned pilot whale Globicephala macrorhynchus. The putative open-reading frame encoded a 397-amino acid protein [pilot whale urea transporter A2 (whUT-A2)] that has 94% amino acid sequence identity to the A2 isoform of the human urea transporter (hUT-A2). Heterologous expression of whUT-A2 cRNA in Xenopus oocytes induced phloretin-inhibitable urea transport. Although Northern analysis and RT-PCR indicated that whUT-A2 was exclusively expressed in kidney, Western blotting using a polyclonal antibody to rat UT-A1/UT-A2 detected various immunoreactive proteins in kidney and other tissues. Furthermore, RT-PCR analysis suggested the presence of alternatively spliced UT-A transcripts in the kidney as well as extrarenal tissues. We conclude that renal urea transporters are highly conserved among mammals inhabiting terrestrial and pelagic environments. A urea-based concentrating mechanism, presumably evolved to meet the demands of an arid terrestrial environment, may have contributed a fortuitous preadaptation that enabled the ancestors of cetaceans to reinvade the sea.

Amino Acid Sequence↗