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Biomedical subjects

A C Schoolwerth

Publications and source records attributed to A C Schoolwerth.

At least 55 records · Page 3Linked to original sources
PubMed1988

Renal gluconeogenesis.

Gluconeogenesis, the de novo formation of glucose from non-carbohydrate precursors, is confined to the proximal convoluted and proximal straight tubules of the mammalian kidney. Compared to liver, renal gluconeogenesis has different substrate requirements and responds to different regulatory stimuli. Stimuli in kidney include starvation, metabolic acidosis, glucocorticoid treatment, and, possibly, PTH and catecholamines. Regulation of gluconeogenic flux occurs at three or four key enzyme sites, particularly phosphoenolpyruvate carboxykinase (PEPCK) and fructose 1,6-bisphosphatase. Interest has focused on the relation among H+, Ca2+, and cyclic AMP in the hormonal regulation of gluconeogenesis. The importance of other putative regulators including fructose 2,6-bisphosphate remains to be determined.

Gluconeogenesis↗
PubMed1986

Cefoperazone for empiric therapy in patients with impaired renal function.

Thirty-five patients with serious infections and impaired renal function were treated empirically with 2 to 8 g of cefoperazone per day. Infections included sepsis in 14, nonbacteremic urinary infections in nine, pneumonia in five, intra-abdominal infection in five, fasciitis in one, and malignant otitis externa in one. The average age of this group was 64.3 years, 25 had ultimately fatal underlying diseases, and their average serum creatinine level was 5.2 mg/dl. Infections were caused by Enterobacteriaceae in 23 patients, Streptococcus faecalis in five, Pseudomonas aeruginosa in four, Staphylococcus aureus in four, Hemophilus influenzae in three, and Staphylococcus epidermidis, Streptococcus pneumoniae, and Clostridium sordelli in one each. Overall, 32 patients had clinical and microbiologic cures, two had improvement, and one had failure. Hypoprothrombinemia occurred in 18 of 28 patients not given vitamin K for prophylaxis and occurred more often in those with serum albumin concentrations below 3.5 g/dl. Prothrombin times returned to normal within 36 hours of treatment with vitamin K, although two patients experienced mild hematemesis. In anicteric patients with liver function abnormalities, 2 g every 12 hours produced peak and trough serum concentrations that averaged 254 and 125 micrograms/ml, respectively, compared with 179.5 and 19.5 micrograms/ml, respectively, in five with normal liver function test results. In jaundiced patients treated with 1 g every 12 hours, trough concentrations were comparably elevated. Serum concentrations did not correlate with hypoprothrombinemia, but high levels throughout the dosing interval may have contributed to the excellent cure rate in this study.

Acute Kidney Injury↗
PubMed1986

gamma-Glutamyl transpeptidase excretion in cisplatin-induced acute renal failure.

Cisplatin (cisdiamminedichloroplatinum), an important antineoplastic agent, possesses nephrotoxicity as its major side effect. A mild partially reversible nonoliguric form of acute renal failure (ARF) is generally the most common form of nephrotoxicity and occurs in experimental animals following a single dose. gamma-Glutamyl transpeptidase (gamma GT) is an enzyme with maximal activity located in the brush border of proximal renal tubular epithelium. To test the relationship between cisplatin nephrotoxicity and urinary gamma GT excretion, rats received a single 5.5 mg/kg dose of cisplatin and gamma GT excretion was evaluated and compared to anatomic and functional damage. Twenty-four hours following cisplatin administration, there was a marked enhancement of urinary gamma GT excretion, prior to the onset of azotemia. Urinary gamma GT excretion peaked at day 4, then returned to baseline, and decreased to values below baseline on days 8 through 10. By days 11 through 12, renal function and urinary gamma GT excretion had returned to normal. The correlation between nephrotoxicity, changes in urinary gamma GT excretion, and anatomic damage was excellent. Morphologically, increased gamma GT excretion was associated with loss of microvilli, and the return of urinary gamma GT excretion to normal correlated with their regeneration. We conclude that cisplatin administration results in increased urinary gamma GT excretion. This early enhancement, prior to the onset of azotemia, may provide a useful noninvasive marker of early cisplatin nephrotoxicity.

Acute Kidney Injury↗
PubMed1986

A servo-system for constant pressure perfusion of the isolated rat kidney.

A technical difficulty in perfusion of the isolated rat kidney has been the regulation of perfusion pressure. Since perfusion pressure is an important determinant of renal function, this parameter should be well regulated for experimental consistency. A servo-system is described that uses analog circuitry to calculate and maintain the cannula tip pressure for perfusion of the isolated kidney. The system is sufficiently responsive to maintain a constant perfusion pressure during the rapid changes in renal resistance caused by addition of angiotensin II or epinephrine to the perfusate. Analog outputs are provided for the recording of perfusion flow rate, perfusion pressure, and renal resistance.

Animals↗
PubMed1985

Effect of bicarbonate on glutamine and glutamate metabolism by rat kidney cortex mitochondria.

Isolated rat kidney cortex mitochondria were incubated at pH 7.4 in the presence or absence of a CO2/bicarbonate buffer (28 mM) to investigate the pH-independent role of bicarbonate on glutamine and glutamate metabolism. Changes in the concentration of key intermediates and products during the incubations were used to calculate metabolite flux rates through specific mitochondrial enzymes. With 1 mM glutamine and 2 mM glutamate as substrates, bicarbonate caused an inhibition of glutamate oxalacetate transaminase flux and a stimulation of glutamate deamination. The same effects were also produced with addition of either aminooxyacetate or malonate. These effects of bicarbonate were prevented when 0.2 mM malate was included as an additional substrate. Bicarbonate ion was identified as a potent competitive inhibitor of rat kidney cortex succinate dehydrogenase. These results indicate that aminooxyacetate, malonate, and bicarbonate all act to stimulate glutamate deamination through a suppression of glutamate transamination, and that the control by transamination of glutamate deamination is due to alterations in alpha-ketoglutarate metabolism. In contrast, in mitochondria incubated with glutamine in the absence of glutamate, bicarbonate was found to inhibit glutamate dehydrogenase flux. This effect was found to be due in part to the lower intramitochondrial pH observed in incubations with bicarbonate. These findings indicate that bicarbonate ion, independent of pH, may have an important regulatory role in renal glutamine and glutamate metabolism.

Aminooxyacetic Acid↗
PubMed1984

The significance of the attachment of rat kidney glutaminase to the inner mitochondrial membrane.

The inner mitochondrial membrane of rat kidney mitochondria was altered by 0.03% Triton X-100 treatment in such a way as to render it permeable to NAD and CoA molecules without release of phosphate-dependent glutaminase. A break of linearity in the Arrhenius plot of the enzyme activity was characteristic for a conformational change of a membrane-bound enzyme. The activity of phosphate-dependent glutaminase immobilized in the inner mitochondrial membrane, as studied in 0.03% Triton X-100-treated mitochondria, and solubilized, as in the supernatant of sonicated mitochondria, was hyperbolic with respect to glutamine concentration. Under optimal conditions (pH 8.6 and 100 mM phosphate) the Vmax and Km were 216 +/- 12 nmol/mg per min and 2.7 +/- 0.4 mM, respectively, for Triton X-100-treated mitochondria, and 121 +/- 8 nmol/mg per min and 15.9 +/- 1.8 mM for sonicated mitochondria. Under near physiological conditions (pH 7.8 and 20 mM phosphate), distinct differences in phosphate-dependent glutaminase kinetics were observed. The Vmax as 29.8 +/- 0.4 and 2.6 /- 0.3 nmol/mg per min and the apparent Km 1.55 +/- 0.06 and 24.5 +/- 6.6 mM for Triton X-100 and sonicated mitochondria, respectively. The sigmoidal activation by phosphate at pH 7.8 was significantly shifted to the left in Triton X-100-treated as compared to sonicated mitochondria. As opposed to the data obtained in sonicated mitochondria, the kinetics of phosphate-dependent glutaminase in 0.03% Triton X-100-treated mitochondria agreed quite well with those obtained in intact, rotenone-inhibited and metabolically active mitochondria. These results suggest that an attachment of phosphate-dependent glutaminase to the inner membrane of kidney mitochondria has a profound effect on its kinetics, particularly under near physiological conditions.

Animals↗
PubMed1984

Carbon tetrachloride nephrotoxicity: a reassessment of pathophysiology based upon the urinary diagnostic indices.

Inhalation or ingestion of carbon tetrachloride (CCl4) has been said to result in the nephrotoxic lesion of acute tubular necrosis (ATN). We describe three patients who inhaled toxic quantities of CCl4 and presented with oligoanuria and severe hepatoxicity. All patients developed protracted vomiting and were unable to maintain fluid intake for several days prior to our evaluation. Physical examination, urinalysis, and calculated FENa, FEH2O, and renal failure index (RFI) indicated that the acute oliguric renal failure was "prerenal" due to marked extracellular fluid (ECF) volume contraction. Aggressive volume repletion restored renal function to normal in each patient. It is suggested that the acute renal failure following CCl4 exposure begins as a functional disorder and may progress to ATN if volume depletion is not recognized and corrected. Early and aggressive volume repletion will reverse this prerenal state and may prevent the later onset of ATN following CCl4 exposure.

Acute Kidney Injury↗
PubMed1984

Wegener's granulomatosis with delayed pulmonary and colonic involvement.

We have described a patient with Wegener's granulomatosis whose renal manifestations preceded the pulmonary findings by six years. The disease remained undiagnosed because renal transplantation required the institution of azathioprine and prednisone therapy. After immunosuppressive (azathioprine) therapy was discontinued, pulmonary, bowel, and cutaneous vasculitis promptly appeared and the diagnosis of WG was finally made. Autopsy showed complete disease remission induced by cyclophosphamide. This case emphasizes the need for intensive follow-up of patients who have glomerulonephritis of undetermined etiology. We believe the diagnosis of WG should be considered in such patients even if objective pulmonary disease is not present initially. In addition to delayed pulmonary manifestations in WG, we have described heretofore unreported colonic vasculitis with associated multiple bowel wall perforations.

Adult↗
PubMed1984

Effect of pH on glutamate efflux from rat kidney mitochondria.

To provide further insight into the relationship between glutamate transport and metabolism in rat kidney mitochondria, the effect of pH on [U-14C]-glutamate efflux from [U-14C]glutamate-loaded mitochondria was tested. Glutamate efflux, measured in rotenone-inhibited energized mitochondria at 28 degrees C, was first order with respect to matrix glutamate. Glutamate efflux was tested at different medium pH values ranging from 6.4 to 7.9. Efflux was fastest at pH 7.9 with a rate constant of 0.988 min-1 and decreased progressively at lower pH values such that the rate constant at pH 6.4 was 0.359 min-1. A highly significant correlation between pH and the rate constant of glutamate efflux was observed. When medium pH was held constant at 7.0, matrix pH (range pH 7.2-8.4) did not affect the rate of glutamate efflux. The reduction in glutamate efflux at low pH provides an explanation for the increased concentration of glutamate observed in the mitochondrial matrix space of isolated rat kidney mitochondria incubated at acid medium pH. The elevated glutamate concentration in turn contributes to the accelerated oxidative deamination of glutamate by glutamate dehydrogenase at acid pH. Moreover, these findings suggest that the reduction in renal cortex glutamate levels observed in acute acidosis in vivo may be explained by a decreased rate of glutamate transport from mitochondria to cytosol coupled with an augmented rate of glutamate oxidation in the matrix.

Animals↗
PubMed1984

Evaluation of proteinuria.

Proteinuria may be the initial manifestation of serious renal disease or merely a laboratory finding of little clinical importance. Excretion of urinary protein in excess of 150 mg per 24 hours in an adult is abnormal. It may be of glomerular, tubular or overflow origin. A comparison of the dipstick and sulfosalicylic acid techniques helps distinguish the source of protein, and electrophoresis is confirmatory. Transient and intermittent proteinuria are not clinically important. Persistent proteinuria requires further investigation.

Benzenesulfonates↗
PubMed1983

Ammonia formation in isolated rat liver mitochondria.

Studies of isolated rat liver mitochondria were undertaken in order to evaluate the importance of glutamate transport, oxidation reduction state, and product inhibition on the rates of formation of ammonia from glutamate. Uptake and efflux of glutamate across the mitochondrial membrane were measured isotopically in the presence of rotenone. Efflux was stimulated by H+ in the mitochondrial matrix and was found to be first order with respect to matrix glutamate except when the matrix pH was unphysiologically low. The data suggest that the Km of matrix glutamate for efflux is decreased by H+. Matrix H+ also appeared to stimulate glutamate uptake, but the effect was to increase both the Km of medium glutamates and Vmax. Mitochondria were incubated at 15 and 28 degrees C with glutamate and malonate. Under these conditions, glutamate was metabolized only by the deamination pathway. Flux was evaluated by assay of ammonia formation. Oxidation reduction state was varied with ADP and uncoupling agents. Matrix alpha-ketoglutarate was varied either by the omission of malonate from the incubation media or by adding alpha-ketoglutarate to the external media. Influx and efflux of glutamate could be calculated from previously determined transport parameters. The difference between calculated influx and efflux was found to be equal to ammonia formation under all conditions. It was, therefore, possible to evaluate the relative contributions of oxidation reduction state, transport, and product inhibition as effectors of ammonia formation. The contribution of transport was relatively small while oxidation reduction state exerted a large influence. alpha-Ketoglutarate was found to be a potent competitive inhibitor of ammonia production and glutamate dehydrogenase. Inhibition of glutamate dehydrogenase by alpha-ketoglutarate was judged to be a potentially important modulator of metabolic fluxes.

Ammonia↗
PubMed1983

Glutamate transprot in rat kidney mitochondria.

The quantitative characteristics of [U-14C]glutamate transport were determined in rotenone-inhibited energized rat kidney mitochondria at pH 7.0 and 28 degrees C. Glutamate efflux was observed to be first order with respect to matrix glutamate with a rate constant of 0.457 min-1. Uptake kinetic studies indicated that the Km of external glutamate was 1.4 mM and the Vmax 3.2 nmol/mg X min. These kinetic values were found to be unchanged at pH 6.6 or in mitochondria obtained from kidneys of chronically acidotic rats. Parallel studies of glutamate deamination were performed in which mitochondria were incubated in state 3, state 4, and with carbonyl cyanide p-trifluoromethoxyphenylhydrazone, in the presence of malonate. The oxidative deamination of glutamate determined with 1 and 10 mM glutamate never exceeded the simultaneously measured rate of glutamate transport. No glutamate was detectable within the mitochondrial matrix under the conditions of these metabolic experiments. The studies indicate that the glutamate hydroxyl transporter is quite slow and rate limiting for the oxidative deamination of external glutamate in rat kidney mitochondria.

Acidosis↗
PubMed1983

Metastatic periosteal osteosarcoma causing cardiac and renal failure.

The case of a 25-year-old man who had periosteal osteogenic sarcoma with intravascular metastases in unusual locations is reported. The patient presented with acute renal failure, unilateral pulmonary edema, functional mitral stenosis, and low cardiac output. After successful surgical removal of a left atrial metastasis with subsequent improvement in cardiac output, renal function improved only transiently and urinary output varied markedly. At autopsy, metastatic osteogenic sarcoma was discovered within the lumen of the abdominal aorta obstructing both renal arteries. The case is the first report of a neoplasm metastatic to the aorta causing intermittent bilateral renal arterial obstruction; it illustrates the diagnostic difficulties presented by intravascular metastatic disease.

Acute Kidney Injury↗