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Biomedical subjects

A Askari

Publications and source records attributed to A Askari.

At least 91 records · Page 5Linked to original sources

(Na+ + K+)-dependent adenosine triphosphatase. Regulation of inorganic phosphate, magnesium ion, and calcium ion interactions with the enzyme by ouabain.

1. (Na+ + K+)-dependent adenosine triphosphatase was phosphorylated on the alpha-subunit by Pi in the presence of Mg2+. Phosphorylation was stimulated by ouabain. The interactions of Pi, Mg2+, and ouabain with the enzyme could be explained by a random terreactant scheme in which the binding of each ligand to the enzyme increased the affinities for the other two. Dissociation constants of all steps of this scheme were estimated. 2. In the presence of Pi and ouabain and without added Mg2+, the phosphoenzyme was formed. Because this could be prevented by ethylenediaminetetraacetic acid, but not ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, phosphoenzyme formation under these conditions was probably dependent on traces of endogenous Mg2+. The ability of this Mg2+ to support phosphorylation could be explained by the large increase in the enzyme's affinity for Mg2+ by ouabain. 3. In the absence of ouabain, Ca2+ did not support phosphorylation and inhibited Mg2+-dependent phosphorylation. At lower concentrations, Ca2+ was competitive with Mg2+. With increasing Ca2+ concentration, negative cooperativity was observed, suggesting the existence of multiple divalent cation sites with equivalent affinities for Mg2+, but varying affinities for Ca2+. 4. In the presence of ouabain, the maximum inhibition of Mg2+-dependent phosphorylation by Ca2+ was 50%. With saturating Pi, Mg2+, and ouabain, the number of sites binding ouabain was equal to the number of sites phosphorylated. Although Ca2+ halved phosphorylation and reduced the affinity for ouabain about 100-fold, it did not affect the number of ouabain sites. 5. We suggest that the enzyme is an alpha-oligomer and that the half-of-the-sites reactivity for phosphorylation in the presence of Pi, Mg2+, ouabain, and optimal Ca2+ is caused by (a) ouabain-induced increase in the affinities of both protomers for Mg2+ and (b) the inability of Ca2+ to replace Mg2+ on one of the protomers.

Animals↗

Origins of the different sensitivities of (Na+ + K+)-dependent adenosinetriphosphatase preparations to ouabain.

Properties of the Na+, K+-ATPase preparations from rat and dog kidney medullae were compared. The two enzymes, with a 1000-fold difference in ouabain sensitivities, had similar subunit compositions and similar K0.5 values and Hill coefficients for substrates and activators of several catalytic activities; suggesting that the structural differences of the two are limited to the ouabain binding domains. Experiments on the interactions of ouabain, Pi, and Mg2+ with the enzymes showed that the two enzymes differed (a) in their inherent affinities for ouabain; and (b) in that Mg2+ binding increased affinity for ouabain to a greater extent in the dog enzyme than in the rat enzyme.

Animals↗

Na+, K+-ATPase: relation of conformational transitions to function.

In its native environment, Na+, K+-ATPase of the plasma membrane is an oligomer consisting of two or more of each of two major subunits. Na+ and K+ move across the membrane through the channels that exist between the catalytic subunits of this oligomer. Two distinct ligand-induced conformational transitions (one due to the binding of K+ and ATP to the enzyme, and the other resulting from the phosphorylation of the enzyme in the presence of Na+ and ATP) cause changes in the geometries of the intersubunit channels, and provide the necessary energy-linked gating mechanisms for the transmembrane movements of ions against electrochemical gradients.

Adenosine Triphosphate↗

Net metabolic changes of zinc, copper, nitrogen, and potassium balances in skeletal trauma patients.

Zinc, copper, nitrogen, and potassium balances of 10 male skeletal trauma patients were determined over 5-6 days each. Nutrition consisted of electrolyte/glucose and/or blood/blood product infusions. Patients were started on balance studies within 24 hr following injury. Zinc and copper were analyzed by atomic absorption while nitrogen was measured by the microKjeldahl technique and potassium by flame photometry. The mean daily balances for these patients were -1563 micrograms zinc, -266 micrograms copper, -20.0 g nitrogen and -29 mEq potassium for 5 patients receiving electrolyte/glucose infusions and +1273 micrograms zinc, +322 micrograms copper, -12.9 g nitrogen, and -26 mEq potassium for 5 patients receiving blood/blood products in addition to electrolyte/glucose. Routine daily maintenance supplementation of 2 mg zinc and 2 mg copper is recommended for skeletal trauma patients on electrolyte/glucose and those on electrolyte/glucose with blood/blood products intravenous infusions. Further balance studies are necessary to ascertain the level of zinc and copper supplementation needed by skeletal trauma patients receiving different nutritional support.

Adolescent↗

Surgical treatment of renovascular disease in the solitary kidney: results in 43 cases.

Renal revascularization was performed on 43 patients with vascular disease involving a solitary kidney. Revascularization was undertaken as treatment for severe hypertension in 35 patients and to preserve renal function in 8. There were 2 operative deaths (4.7 per cent) and 3 major complications (7 per cent). No patient suffered acute renal failure after revascularization. Followup ranges from 6 months to 14 years (mean 6 years). The postoperative serum creatinine is improved in 26 patients (63 per cent), unchanged in 9 (22 per cent) and increased in 6 (15 per cent). Of 35 patients with hypertension the blood pressure is cured in 18 (51 per cent) and improved in 14 (40 per cent); there were 3 (9 per cent) failures. In selected patients with renal artery disease involving a solitary kidney revascularization can provide effective treatment of hypertension and stabilization or improvement of renal function.

Adult↗

(Na+ + K+)-ATPase : phosphorylation-dependent cross-linking of the alpha-subunits in the presence of Ca2+ and o-phenanthroline.

In previous studies we had demonstrated that in the presence of 0.25 mM Cu2+ and 1.25 mM o-phenanthroline, cross-linking of the alpha-subunits of Na+ + K+)-dependent adenosine triphosphatase was induced by the addition of Na+ + ATP, and that the formation of the alpha,alpha-dimer was preceded by that of phosphoenzyme. The purpose of the present studies was the further evaluation of the role of phosphoenzyme in the process of cross-linking. Na+ + UTP did not induce cross-linking unless Mg2+ was also added. In contrast, Na+ + ATP-induced cross-linking did not require the addition of Mg2+. The different effects of ATP and UTP in the absence of added Mg2+ could be accounted for by the presence in the enzyme preparation of bound Mg2+ which supported enzyme phosphorylation by ATP but not by UTP. When the enzyme was phosphorylated by Pi, in the presence of Mg2 and ouabain, and the exposed to Cu2+ and o-phenanthroline, the alpha,alpha-dimer was obtained. Under these conditions, Na+ blocked both phosphorylation and cross-linking. These results indicate that it is the formation of phosphoenzyme per se that leads to conformational transitions favorable to cross-linking. They also suggest that Cu2+ and o-phenanthroline participate in the cross-linking reaction, but not in the phosphorylation reactions. In the digitonin-treated enzyme, Na+ and ATP induced the formation of phosphoenzyme, but not that of alpha,alpha-dimer. These findings indicate that in addition to phosphorylation, a proper orientation o alpha-subunits in an oligomer is also necessary for cross-linking.

Adenosine Triphosphate↗

Relationship between the positive inotropic effect of ouabain and its inhibitory effects on Na+, K+ -ATPase and active transport of Rb+ in the dog heart.

Two previous reports have indicated that in the dog if sustained positive inotropy without arrhythmias is induced by ouabain infusion, inhibition of myocardial Na+, K+-activated adenosine triphosphatase is not observed. Another previous study has shown that in similar experiments induction of sustained inotropy is accompanied by inhibition of the active uptake of Rb+. To resolve the apparent inconsistencies between these findings, we repeated the experiments and measured the inhibition of the enzyme and the inhibition of Rb+ uptake after the induction of sustained inotropy with ouabain. Utilizing three different ouabain dosage regimens in open-chested dogs, we obtained three different quasi-steady state plasma levels of ouabain. At the highest level, ouabain toxicity accompanied by enzyme inhibition and inhibition to RB+ uptake was observed. With the intermediate levels, positive inotropy without significant toxicity was also accompanied by enzyme inhibition and the inhibition of Rb+ uptake. At the lowest ouabain plasma levels, sustained positive inotropy without significant inhibition of either enzyme activity or +b+ uptake was obtained. The data indicate that in this preparation either a small degree of enzyme inhibition, which is difficult to detect is sufficient to produce pronounced positive inotropy, or that the inhibition of the enzyme is not required for the induction of positive inotropy.

Animals↗

Metastatic carcinoma to testicle.

Metastatic carcinoma to the testicular, epididymis, and their tunics is unusual and adenocarcinoma of the small bowel is extremely rare. The combination of primary adenocarcinoma of the jejunum with metastasis to the tunica vaginalis of the testis has not been reported previously. An unusual case of a sacral mass in a twenty-seven-year-old black man is presented and the literature reviewed.

Adenocarcinoma↗

Red cell surface antigen and its relationship to survival of patients with transitional cell carcinoma of the bladder.

We studied 73 patients with transitional cell carcinoma of the bladder seen from 1967 to 1973. The red cell antigen test was done in a controlled blind study to determine if tumor behavior can be predicted by this test. Our results do not substantiate the findings of other investigators who have reported excellent correlation. We did not find statistical evidence that loss of antigen could be equated to a poor prognosis. We noted that patients in group O gave the weakest reaction and that this test had to be done in a modified fashion in tumors from these patients. It also was noted that as individuals age they tend to lose the red cell antigen. There is no doubt that this test, as reported in the literature, is a great advance in the study of bladder cancer. Further refinement in technique and more data are needed to substantiate its accuracy in predicting the behavior of bladder cancer.

ABO Blood-Group System↗

Pyeloureteritis cystica.

A case of pyeloureteritis cystica is presented. The incidental findings of an episode of hypertension focused attention on the urinary system. Urologic evaluation concluded a suspicious renal mass. The diagnosis was established only after histologic studies of the surgical specimen.

Cysts↗

Late ureteral obstruction and hematuria from de novo angiosarcoma in a renal transplant patient.

A patient is described with a long-term functioning renal allograft who presented with ureteral obstruction and hematuria from an angiosarcoma. The diagnosis of ureteral obstruction was established preoperatively with computerized tomography guided anterograde pyelography. This represents the first documented case of an angiosarcoma occurring de novo in a renal allograft recipient. Continued awareness is needed of the increased risk of malignancy following transplantation.

Adult↗