Autosomal recessive distal renal tubular acidosis (dRTA) is a severe disorder of acid-base homeostasis, often accompanied by sensorineural deafness. We and others have previously shown that mutations in the tissue-restricted a4 and B1 subunits of the H(+)-ATPase underlie this syndrome. Here, we describe an Atp6v0a4 knockout mouse, which lacks the a4 subunit. Using β-galactosidase as a reporter ...

We investigated the applicability of liquid chromatography with photodiode array detection as a serum drug screening technique in an emergency toxicology setting. Basic compounds are extracted from alkalinized serum with hexane and chromatographed on a cyanopropyl reversed-phase column. The photodiode array detector records the ultraviolet spectrum of each eluting peak for identification and qu...

The E5 oncoprotein of bovine papillomavirus type I is a small, hydrophobic polypeptide localized predominantly in the Golgi complex. E5-mediated transformation is often associated with activation of the PDGF receptor (PDGF-R). However, some E5 mutants fail to induce PDGF-R phosphorylation yet retain transforming activity, suggesting an additional mechanism of action. Since E5 also interacts wit...

Lysosomal enzymes function optimally at low pH; as accumulation of waste material contributes to cell aging and disease, dysregulation of lysosomal pH may represent an early step in several pathologies. Here, we demonstrate that stimulation of the P2X7 receptor (P2X7R) for ATP alkalinizes lysosomes in cultured human retinal pigmented epithelial (RPE) cells and impairs lysosomal function. P2X7R ...

1. Metabolic acidosis invariably accompanies chronic renal failure, and short periods of metabolic acidosis cause renal growth and proteinuria in normal rats. Rates of ammoniagenesis are increased in chronic renal failure, and it has been suggested that this contributes to disease progression. This study assessed (i) whether prolonged acidosis causes chronic renal injury in the normal kidney an...

Introduction Drug-sensitive and drug-resistant MCF7 tumor xenografts in SCID mice have a lower extracellular pH (pHe) than intracellular pH (pHi) (1). Such an acid-outside pH gradient acts to exclude weak-base species such as the commonly used drugs mitoxantrone and doxorubicin (2). We have recently shown that the extracellular milieu of MCF7 tumor xenografts in SCID mice can be alkalinized by ...

We report an analytical reversed-phase liquid-chromatographic procedure for quantifying nicotine and cotinine in urine, taking into account the presence of interfering caffeine frequently encountered in such specimens. These analytes are extracted from the alkalinized urine with chloroform. After evaporation of the chloroform, the residue is dissolved in methanol and injected into a chromatogra...

Several conditions, including rhabdomyolysis, trauma, and surgery, are associated with the release of large amounts of myoglobin into the circulation. Saturation of the salvage system of the kidney will produce myoglobinuria, a condition associated with acute renal failure (ARF). The exact mechanism is not known, but precipitation of myoglobin in the tubules and myoglobin-mediated formation of ...

At present, leucine-induced hypoglycemia and maple-syrup urine disease are the only inborn errors of leucine metabolism recognized in man. In the former disorder, recurrent hypoglycemia is the result of leucine-induced hyperinsulinism.1 In maple-syrup urine disease there is a block in the oxidative decarboxylation of leucine, isoleucine, and valine resulting in the accumulation of the amino aci...