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Biomedical subjects

O Sperling

Publications and source records attributed to O Sperling.

At least 55 records · Page 3Linked to original sources
PubMed1989

Guanine ribonucleotide metabolism in human red blood cells: evidence for a high rate of GMP dephosphorylation.

The flux rates through the metabolic pathways affecting the maintenance of GuRN pool in intact human RBC were studied. Normal RBC, incubated in KRBB, exhibited a markedly higher accumulation in nucleotides of Gu than of Hx. Addition of 8-AGuo, a potent inhibitor of PNP, resulted in a marked increase in the accumulation of label in the nucleosides, in Ino following incubation with Hx, and in Guo following incubation with Gu, indicating a very high rate of IMP and GMP degradation to bases through their respective nucleosides. Most of the degradation of GMP is by dephosphorylation to Guo, rather than through reductive deamination to IMP. The ultimate fate of IMP in RBC is its degradation to Ino and consequently to Hx. The contribution of AdRN or of IMP to the GuRN pool is negligible. The results indicate that concerning IMP and GMP, human RBC contain very active futile cycles, nucleotide----nucleoside----base----nucleotide, catalyzed by 5'-nucleotidase, PNP, and HGPRT. The operation of the complete cycles is essential for the maintenance of GuRN and the IMP pool size. These results may explain the finding of reduced GTP content in RBC from patients with an inborn deficiency of PNP or of HGPRT.

Erythrocytes↗
PubMed1989

Does determination of serum aspartate aminotransferase contribute to the diagnosis of acute myocardial infarction?

Values for total lactate dehydrogenase (LD), LD isoenzymes, and serum aspartate aminotransferase (AST) were determined in 150 patients with acute myocardial infarction (AMI) and 130 non-AMI patients 24, 48, and 72 hours after admission. The authors assessed the diagnostic yield of a single determination of AST, LD, and three LD isoenzymes tests: LD-1 greater than LD-2; LD-1 greater than 90 U/L; LD-1/LD greater than 0.4. They also assessed the diagnostic accuracy of combined determination of AST with LD and AST with each of the above three LD isoenzymes tests. The efficiency of single determination of AST was better than that of LD (88% vs. 80%, 48 hours after admission). The most efficient single test for diagnosing AMI was the LD-1 greater than 90 U/L test (92%, 48 hours after admission). The efficiency of the combined AST/LD test was better than that of a single determination of each of the two enzymes (90% vs. 88% and 80%, 48 hours after admission). The highest efficiency was achieved, however, with combined determination of AST and any of the three LD isoenzymes tests. It was found to be more efficient than single determination of each of the LD isoenzymes tests (95.5-96% vs. 89-92.5%) and more efficient than the combined determination of the AST/LD test (95.5-96% vs. 89-90%). The authors conclude that AST should be determined in every patient with suspected AMI because its determination may contribute to the diagnostic yield of LD isoenzymes tests, especially in patients with AMI admitted 48-72 hours after onset of symptoms, when creatine kinase declined to near normal values.

Adult↗
PubMed1989

Patterns of lactate dehydrogenase isoenzymes 1 and 2 in serum of patients performing an exercise test.

Values for total lactate dehydrogenase (LD, EC 1.1.1.27) activity and LD isoenzymes were determined in serum from 56 patients and 40 healthy subjects before and 24, 48, and 72 h after they performed an exercise test. The mean (for all four times) total LD activity concentration and proportion of LD-2 were within the normal range for all 96 subjects. Mean LD-1 values for serum, although within the normal range in all subjects, were significantly higher in patients with positive exercise test results than in subjects with negative results: 75 (SD 12) U/L in 35 patients with ST depression greater than 2 mm; 63 (SD 14) U/L in 16 patients with ST depression of 1-2 mm; 43 (SD 11) U/L in subjects with negative test results, by 48 h after the test. The LD 1:2 ratio was also markedly higher in the group of patients with positive test exercise results, especially in those with ST depression greater than 2 mm (1.02, SD 0.06), compared with those subjects with negative results (0.60, SD 0.04). A similar trend was also found 24 and 72 h after the exercise test. We conclude that exercise-myocardial ischemia may lead to an increased LD 1:2 ratio in serum, and demonstrate a correlation between the degree of ischemia and the LD 1:2 ratio. Determination of the LD 1:2 ratio, even in the presence of normal total LD activity, may assist in the clinical evaluation of patients performing an exercise test.

Adult↗
PubMed1988

Pathways of adenine nucleotide catabolism in primary rat cardiomyocyte cultures.

The pathways of adenine nucleotide catabolism were investigated in cultured beating cardiomyocytes. The activity of the enzymes involved in AMP degradation was assayed in cell extracts. Fluxes of label from ATP to the various purine derivatives were measured in intact cells. Under physiological conditions, cells degraded AMP through deamination to IMP. IMP was rapidly degraded to inosine, hypoxanthine, xanthine and uric acid, which were effluxed from the cells. This is in accord with the fact that the activity of AMP deaminase (EC 3.5.4.6) was 7-fold that of AMP 5'-Nucleotidase (EC 3.1.3.5). Mild ATP-degradation, induced by inhibition of glycolysis by iodoacetate, caused no alterations in the degradation pathways (more than 85% through deamination to IMP). However, fast ATP-degradation (83% of adenine nucleotides/10 min), induced by simultaneous inhibition of glycolysis and electron transport (by antimycin A), caused increased dephosphorylation of AMP to adenosine (50% of total AMP-degradation). The cardiomyocyte extracts were found to contain a significant activity of purine nucleoside phosphorylase (EC 2.4.2.1). Despite the presence of hypoxanthine-guanine phosphoribosyltransferase (EC 2.4.2.8), salvage of hypoxanthine to IMP, both at physiological as well as at conditions associated with ATP degradation, was slow. The salvage of adenosine appeared to be efficient at physiological conditions, but not at fast rates of ATP degradation.

Adenine Nucleotides↗
PubMed1988

Total lactate dehydrogenase and its isoenzymes in serum of patients with non-small-cell lung cancer.

Values for total lactate dehydrogenase (LD, EC 1.1.1.27) activity in serum and LD isoenzymes were determined at diagnosis in 273 patients with non-small-cell lung cancer, 85 of whom were in stage 1, 92 in stage 2, and 96 in stage 3. We divided the patients into three groups, based on their total serum LD values: less than 225 U/L (normal reference range), 226-500 U/L, and greater than 500 U/L. Overall values for LD were above normal at diagnosis for 69% of the patients, being moderately increased in 63 patients and highly increased in 125. Eighty percent of the patients in stage 1 had normal values for LD at diagnosis, but 88% of the patients in stage 2 and 94% of the patients in stage 3 had above-normal LD values at diagnosis. In 55% of the patients in stage 2 and 73% of the patients in stage 3, LD activity was highly increased. In the patients with normal values for total LD, the proportions of the LD isoenzymes were normal. In the patients with increased LD, the isoenzyme proportions were increased for LD-4 and LD-5, up to twice the normal values. The sensitivity of LD in detection of lung cancer was 60% for LD at the cutoff point of 250 U/L in comparison with normal controls, and 47% for LD at the cutoff point of 310 U/L in comparison with the benign lung disease group of patients (95% specificity). We conclude that total LD in serum may be a direct indicator of clinical stage and tumor burden in patients with non-small-cell lung cancer.

Adenocarcinoma↗
PubMed1988

Atypical patterns of lactate dehydrogenase isoenzymes in acute myocardial infarction.

Total lactate dehydrogenase (LD; EC 1.1.1.27) activity in serum and LD isoenzymes were quantified in 190 patients with acute myocardial infarction (AMI) 24, 48, and 72 h after admission. In 90% of the 570 blood specimens an LD isoenzyme pattern typical of AMI (LD-1/LD-2 greater than 0.76) was found. The other 56 blood specimens showed an LD isoenzyme pattern atypical of AMI (LD-1/LD-2 less than 0.76). They were divided into three groups: 28 specimens with isomorphic pattern (relative increase in all five LD isoenzymes); 18 with relatively increased LD-3 proportion (greater than 35%); and 10 specimens with increased LD-5 proportion (greater than 10%). No difference was found in mean total LD activity in serum between the typical isoenzyme group and the three atypical groups. The LD isomorphic pattern was found in 60% of AMI patients complicated by cardiogenic shock. Fifty percent of AMI patients admitted with pulmonary edema showed increased LD-3 proportion and half of the patients with AMI and congestive heart failure, predominant right, demonstrated increased LD-5 proportion. We conclude that although most patients with AMI present at diagnosis with a typical LD isoenzyme pattern, it is important to recognize that some may present with atypical LD isoenzyme patterns, which may be associated with specific AMI complications.

Adult↗
PubMed1988

Significance of isolated increases in total lactate dehydrogenase and its isoenzymes in serum of patients with bacterial pneumonia.

Total lactate dehydrogenase (LD, EC 1.1.1.27) activity in serum and LD isoenzymes were quantified at the time of diagnosis in 320 patients with bacterial pneumonia. In eighty, LD activity was increased, but this was accompanied by either other pathological results for liver-function tests or associated diseases that could explain it. The remaining 240 patients were divided into four groups, based on their total serum LD values: group A, less than 225 U/L (normal limit); group B, 226-350 U/L; group C, 351-499 U/L; and group D, greater than 500 U/L. Total LD was above normal at diagnosis in 40% of the patients. Recovery time was twice as long in group D as in groups A, B, and C. In five patients from group D, the pneumonia reflected underlying lung cancer. In groups B and C, the LD-3 ratio was increased in comparison with group A; in group D, LD-4 and LD-5 were increased up to twice the normal limit. Evidently nearly half of patients with bacterial pneumonia may show isolated increases in total LD activity (mostly LD-3) in serum. In cases with high activity, prolonged recovery time is expected. Intensive follow-up and extensive investigation are warranted in these patients, because some may have underlying lung cancer.

Aged↗
PubMed1988

The efficiency of lactate dehydrogenase isoenzyme determination for the diagnosis of acute myocardial infarction.

Values for total lactate dehydrogenase (LDH; EC 1.1.1.27) activity and LDH isoenzymes 1 and 2 were determined in 80 patients with acute myocardial infarction (AMI) and in 40 without AMI every 24 hours up to 15 days after admission, when total serum LDH level returned to normal. The sensitivity, specificity, and efficiency of three LDH isoenzyme factors (LDH-1, greater than 90 U/L; LDH-1 greater than LDH-2; LDH-1/LDH ratio, greater than 0.4) for diagnosing AMI were assessed in three groups of patients according to total serum LDH values--group A, LDH level over 600 U/L; group B, 400 to 599 U/L; group C, 225 to 399 U/L--and in five groups of patients according to the time after admission--(1) first 48 hours; (2) three to five days; (3) six to eight days; (4) nine to 11 days; (5) 12 to 15 days. All three factors were found to be highly efficient for diagnosing AMI (91.5% to 97.5%) in groups A and B, but the most efficient factor in each group was LDH-1 value above 90 U/L. In group C, the only efficient factor was the LDH-1 value over 90 U/L (96%). The most efficient factor for diagnosing AMI in relation to time after admission up to 15 days after AMI was the LDH-1 value over 90 U/L (96% to 97.5%). The factors LDH-1 greater than LDH-2 and LDH-1/LDH above 0.4 were more efficient in patients up to five days after AMI (91.5% to 97.5%) than in patients six to 15 days after admission. We conclude that the most efficient LDH value for diagnosing AMI is the absolute value of LDH-1 above 90 U/L. Its superiority over other LDH isoenzyme values is best documented in a group of patients six to 15 days after admission and with only slight to moderate elevation of total serum LDH values (225 to 399 U/L).

Adult↗
PubMed1988

Patterns of lactate dehydrogenase isoenzymes in serum of patients with acute pulmonary edema.

Total lactate dehydrogenase (LD; EC 1.1.1.27) activity in serum and proportions of LD isoenzymes were quantified on admission and discharge in 170 selected (from 240) patients with acute pulmonary edema (APE). The patients were divided into group A, 75 patients with normal LD values (less than 225 U/L); and groups B-E, with increased LD activity in serum: group B, 40 patients with increase in the proportion of LD-3 (greater than 38%); group C, 12 patients with increased LD-5; group D, 36 patients with an isomorphic pattern of LD isoenzymes; and group E, seven patients with LD-1/LD-2 greater than 0.75. Nine patients in group C (75%) had also signs of right-sided congestive heart failure, 30 in group D (83%) had hypotension on admission, and six in group E (86%) had signs of recent myocardial infarction. Evidently, half of patients with APE may show increased total LD activity in serum at the time of admission. LD isoenzyme proportions should be determined in such patients, because there is no one typical pattern of LD isoenzymes and some LD isoenzyme patterns may be associated with specific clinical situations.

Acute Disease↗
PubMed1987

Pathways of adenine nucleotide catabolism in primary rat muscle cultures.

The pathways of AMP degradation and the metabolic fate of adenosine were studied in cultured myotubes under physiological conditions and during artificially induced enhanced degradation of ATP. The metabolic pathways were gauged by tracing the flow of radioactivity from ATP, prelabelled by incubation of the cultures with [14C]adenine, into the various purine derivatives. The fractional flow from AMP to inosine through adenosine was estimated by the use of the adenosine deaminase (EC 3.5.4.4) inhibitors, coformycin and 2'-deoxycoformycin. The activities of the enzymes involved with AMP and adenosine metabolism were determined in cell extracts. The results demonstrate that under physiological conditions, there is a small but significant flow of label from ATP to diffusible bases and nucleosides, most of which are effluxed to the incubation medium. This catabolic flow is mediated almost exclusively by the activity of AMP deaminase (EC 3.5.4.6), rather than by AMP 5'-nucleotidase (EC 3.1.3.5), reflecting the markedly higher Vmax/Km ratio for the deaminase. Enhancement of ATP degradation by inhibition of glycolysis or by combined inhibition of glycolysis and of electron transport resulted in a markedly greater flux of label from adenine nucleotides to nucleosides and bases, but did not alter significantly the ratio between AMP deamination and AMP dephosphorylation, which remained around 19:1. Combined inhibition of glycolysis and of electron transport resulted, in addition, in accumulation of label in IMP, reaching about 20% of total AMP degraded. In the intact myotubes at low adenosine concentration, the anabolic activity of adenosine kinase was at least 4.9-fold the catabolic activity of adenosine deaminase, in accord with the markedly higher Vmax/Km ratio of the kinase for adenosine. The results indicate the operation in the myotube cultures, under various rates of ATP degradation, of the AMP to IMP limb of the purine nucleotide cycle. On the other hand, the formation of purine bases and nucleosides, representing the majority of degraded ATP, indicates inefficient activity of the IMP to AMP limb of the cycle, as well as inefficient salvage of hypoxanthine under these conditions.

5'-Nucleotidase↗
PubMed1987

Lactate dehydrogenase isoenzymes in serum during recent acute myocardial infarction.

Lactate dehydrogenase (LD, EC 1.1.1.27) isoenzymes 1 and 2 and the LD 1:2 ratio were determined in 62 patients with recent myocardial infarction 24, 48, and 72 h after total serum LD activity had returned to normal values. From the results we could define two groups of patients. The first, 40 patients in whom proportions of LD-1 and LD-2 isoenzymes in serum and the LD 1:2 ratio were all within the normal reference interval, all had an uncomplicated course of recovery from myocardial infarction. In the remaining 22 patients, LD-1 still exceeded LD-2 24 to 72 h after total LD activity returned to normal values; i.e., the ratio was similar to that in patients with myocardial infarction. Seven of these 22 patients (32%) had a complicated course, with re-infarction in all seven. Thus, even in the presence of normal total LD activity, a high LD 1:2 ratio may reflect a consistent focal myocardial necrosis in some patients with recent myocardial infarction and may serve as an early marker for further re-infarction.

Adult↗
PubMed1986

"Flipped" lactic dehydrogenase pattern in acute coronary insufficiency.

Serum lactic dehydrogenase (LDH) isoenzymes were measured 24, 48, and 72 hours after administration in 85 patients with acute coronary insufficiency (ACI) and 10 patients with stable angina pectoris who served as controls. The above patients did not develop myocardial infarction according to the criteria of development of new Q waves or elevation of cardiac enzymes. In 15 patients with ACI a "flipped" LDH pattern (LDH1 greater than LDH2) was found in the presence of normal total LDH activity and normal creatine kinase-MB. The values of LDH 1:2 ratio ranged between 1.02 and 1.13 (normal values 0.45-0.75). In the 10 control patients, normal levels of total LDH and normal LDH enzyme distribution and creatine kinase-MB were found. A possible explanation for the flipped LDH pattern in the ACI patients (indicating some myocardial damage) could be myocytolysis and coagulation necrosis found on postmortem examinations. The conclusion of our study is that LDH isoenzymes should be measured in patients with ACI to determine the LDH 1:2 ratio. The finding of a "flipped" LDH pattern demonstrating myocardial damage, lacking in stable angina, may also be helpful in patients who developed the clinical picture of ACI more than 24 hours before arrival at the hospital, since by that time the creatine kinase-MB may have already returned to normal. An additional advantage of measuring LDH isoenzymes in these patients may be that patients with "flipped" LDH pattern may need a longer rest and earlier coronary angiographic evaluation.

Acute Disease↗