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Renal Tubular Acidosis (renal + tubular_acidosis)
Selected AbstractsRenal Tubular Acidosis Associated With Zonisamide TherapyEPILEPSIA, Issue 1 2000Article first published online: 19 SEP 200 First page of article [source] Type 1 (distal) renal tubular acidosis in a patient with Type 1 diabetes mellitus,not all cases of metabolic acidosis in Type 1 diabetes mellitus are due to diabetic ketoacidosisDIABETIC MEDICINE, Issue 1 2008J. A. Dymot No abstract is available for this article. [source] Molecular physiology of SLC4 anion exchangersEXPERIMENTAL PHYSIOLOGY, Issue 1 2006Seth L. Alper Plasmalemmal Cl,,HCO3, exchangers regulate intracellular pH and [Cl,] and cell volume. In polarized epithelial cells, they contribute also to transepithelial secretion and reabsorption of acid,base equivalents and of Cl,. Members of both the SLC4 and SLC26 mammalian gene families encode Na+ -independent Cl,,HCO3, exchangers. Human SLC4A1/AE1 mutations cause either the erythroid disorders spherocytic haemolytic anaemia or ovalocytosis, or distal renal tubular acidosis. SLC4A2/AE2 knockout mice die at weaning. Human SLC4A3/AE3 polymorphisms have been associated with seizure disorder. Although mammalian SLC4/AE polypeptides mediate only electroneutral Cl,,anion exchange, trout erythroid AE1 also promotes osmolyte transport and increased anion conductance. Mouse AE1 is required for DIDS-sensitive erythroid Cl, conductance, but definitive evidence for mediation of Cl, conductance is lacking. However, a single missense mutation allows AE1 to mediate both electrogenic SO42,,Cl, exchange or electroneutral, H+ -independent SO42,,SO42, exchange. In the Xenopus oocyte, the AE1 C-terminal cytoplasmic tail residues reported to bind carbonic anhydrase II are dispensable for Cl,,Cl, exchange, but required for Cl,,HCO3, exchange. AE2 is acutely and independently inhibited by intracellular and extracellular H+, and this regulation requires integrity of the most highly conserved sequence of the AE2 N-terminal cytoplasmic domain. Individual missense mutations within this and adjacent regions identify additional residues which acid-shift pHo sensitivity. These regions together are modelled to form contiguous surface patches on the AE2 cytoplasmic domain. In contrast, the N-terminal variant AE2c polypeptide exhibits an alkaline-shifted pHo sensitivity, as do certain transmembrane domain His mutants. AE2-mediated anion exchange is also stimulated by ammonium and by hypertonicity by a mechanism sensitive to inhibition by chelation of intracellular Ca2+ and by calmidazolium. This growing body of structure,function data, together with increased structural information, will advance mechanistic understanding of SLC4 anion exchangers. [source] Familial Hypocalciuric Hypercalcemia Caused by an R648stop Mutation in the Calcium-Sensing Receptor Gene ,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 12 2002Mika Yamauchi Abstract In this study, we report an 84-year-old female proband in a Japanese family with familial hypocalciuric hypercalcemia (FHH) caused by an R648stop mutation in the extracellular calcium-sensing receptor (CaR) gene. At the age of 71 years, she presented with hypercalcemia (11.4 mg/dl), hypocalciuria (Cca/Ccr = 0.003), hypermagnesemia (2.9 mg/dl), and a high-serum parathyroid hormone (PTH) level (midregion PTH, 3225 [160,520] pg/ml). At the age of 74 years, a family screening was carried out and revealed a total of 9 hypercalcemic individuals (all intact PTH values <62 pg/dl) among 17 family members tested, thus, being diagnosed as FHH. Two and one-half of three clearly enlarged parathyroid glands were resected, because persistently high PTH levels (intact PTH, 292 pg/ml; midregion PTH, 5225 pg/ml) and the presence of a markedly enlarged parathyroid gland by several imaging modalities (ultrasonography, computed tomography [CT], magnetic resonance imaging [MRI], and subtraction scintigraphy) suggested coexistent primary hyperparathyroidism (pHPT); however, hypercalcemia persisted postoperatively. Histological and immunohistochemical examination revealed that the resected parathyroid glands showed lipohyperplasia as well as normally expressed Ki67, vitamin D receptor (VDR), and the CaR. Sequence analysis disclosed that the proband and all affected family members had a heterozygous nonsense (R648stop) mutation in the CaR gene. This mutation is located in the first intracellular loop; thus, it would be predicted to produce a truncated CaR having only one transmembrane domain (TMD) and lacking its remaining TMDs, intracellular loops, and C-terminal tail. Western analysis of biotinylated HEK293 cells transiently transfected with this mutant receptor showed cell surface expression of the truncated protein at a level comparable with that of the wild-type CaR. The mutant receptor, however, exhibited no increase in intracellular free calcium concentration (Ca2+i) when exposed to high extracellular calcium concentrations (Ca2+o). The proband's clinical course was complicated because of associated renal tubular acidosis (RTA) and nephrotic syndrome. However, it was unclear whether their association affected the development of elevated serum PTH and parathyroid gland enlargement. This report is the first to show that an R648stop CaR mutation yields a truncated receptor that is expressed on the cell surface but is devoid of biological activity, resulting in FHH. [source] Search for occult secondary osteoporosis: impact of identified possible risk factors on bone mineral densityJOURNAL OF INTERNAL MEDICINE, Issue 5 2002H. A. Deutschmann Abstract. Deutschmann HA, Weger M, Weger W, Kotanko P, Deutschmann MJ, Skrabal F (Krankenhaus der Barmherzigen Brüder, Marschallgasse, Teaching Hospital of the Karl-Franzens University Graz, Austria). Search for occult secondary osteoporosis: impact of identified possible risk factors on bone mineral density. J Intern Med 2002; 252: 389,397. Objectives. To determine whether the use of more elaborate diagnostic tests can identify possible risk factors for secondary osteoporosis and to evaluate the impact of these possible risk factors on the severity of bone disease in the study population. Design. Cross-sectional study. Setting and participants. ,We have investigated 377 subjects (285 females, 92 males) with osteoporosis (T-score less than ,2.5 in dual energy X-ray absorption) or nontraumatic lumbar vertebral fractures; these patients were referred to our hospital, a secondary care centre, for evaluation and treatment of osteoporosis. Results. Osteoporosis without attributable risk factor was diagnosed in 106 women (37%) and 30 men (33%). In 241 patients (179 women, 62 men) one or more possible risk factors for osteoporosis (in this paper also called subclinical disease) were revealed. The most common were lactose malabsorption, disturbed exocrine pancreatic function and renal tubular disturbances, including renal hypercalciuria, incomplete renal tubular acidosis and mild phosphate diabetes. The number of possible risk factors in the individual patient was significantly related to the severity of osteoporosis as assessed by Z-scores (Spearman correlation r = ,0.43, P < 0.001, n = 172 for females; r = ,0.28, P < 0.05, n = 65 for males). Conclusions. All the identified subclinical diseases would have remained undetected if the currently accepted guidelines for the investigation of patients with osteoporosis were applied. The statistically significant correlation between the number of identified possible risk factors and the severity of bone disease in the individual patient strongly suggests the pathogenetic significance of the identified subclinical diseases. It is yet to be shown, whether specific treatment of these subclinical diseases yields additional improvement of bone mass as compared with standard treatment of osteoporosis. [source] Hemolytic anemia and distal renal tubular acidosis in two Indian patients homozygous for SLC4A1/AE1 mutation A858D,AMERICAN JOURNAL OF HEMATOLOGY, Issue 10 2010Boris E. Shmukler First page of article [source] Differences in Endolymphatic Sac Mitochondria-Rich Cells Indicate Specific FunctionsTHE LARYNGOSCOPE, Issue 3 2002Theo A. Peters MSc Abstract Objective/Hypothesis The purpose of the study was to examine the specific involvement of endolymphatic sac mitochondria-rich cells in endolymph homeostasis. Study Design Transmission electron microscopy and immunohistochemistry were performed on the endolymphatic sac of young adult rats, and two important developmental stages were also investigated. Methods Ultrastructural characteristics of endolymphatic sac mitochondria-rich cells were studied more concisely and compared with renal mitochondria-rich cells (i.e., the intercalated cells). In addition, expression of cytokeratins 7 and 19 was determined. Results Until birth, only one type of mitochondria-rich cell is observed in the rat endolymphatic sac. In young adult animals, distinct differences in mitochondria-rich cell ultrastructure in the endolymphatic sac enables classification into subtypes or configurations. Comparison of endolymphatic sac mitochondria-rich cells with renal intercalated cells reveals striking similarities and provides additional information on their specific function in endolymph homeostasis. Furthermore, differences in cytokeratin expression are determined in endolymphatic sac mitochondria-rich cells. Conclusions Differences in morphology of endolymphatic sac mitochondria-rich cells develop after birth and may reflect a distinct functional or physiological state of the cell. In analogy to renal intercalated cells, the distribution patterns of H+ -adenosine triphosphatase and Cl,/HCO3, exchanger may differ between subtypes. We propose that subtype A mitochondria-rich cells, from which protruding A mitochondria-rich cells are the activated state, are involved in proton secretion (apical H+ -adenosine triphosphatase) and thus are potential candidates for hearing loss accompanying renal tubular acidosis. Subtype B mitochondria-rich cells are the most likely candidates to be affected in Pendred syndrome because of the assumed function of pendrin as apical Cl,/HCO3, exchanger. [source] Preliminary X-ray diffraction analysis of the cytoplasmic N-terminal domain of the Na/HCO3 cotransporter NBCe1-AACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 6 2006Harindarpal S. Gill The N-terminal cytoplasmic domain of the Na+ -coupled HCO cotransporter NBCe1-A (NtNBCe1) has been linked with proximal renal tubular acidosis. In a previous purification study of recombinant NtNBCe1, crystal growth at a suboptimal protein concentration (<1,mg,ml,1) yielded small single diamond-shaped crystals that diffracted poorly. In the present study, by increasing the protein concentration 50-fold, the crystal size was doubled and robustness was also improved. Crystal annealing made the crystals suitable for X-ray diffraction. The crystals either belong to space group P3121 or P31 with pseudo P3121 symmetry, with unit-cell parameters a = 51.7, b = 51.7, c = 200.6,Å, , = , = 90, , = 120°, and diffract X-rays to 3.0,Å resolution. The calculated Matthews number is 1.9,Å3,Da,1, with two monomers of molecular weight ,83,kDa in the asymmetric unit. The molecular- replacement packing solution shows that the molecules form dimers by a domain-swapping mechanism. [source] | ||||||||||