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A Theologides

Publications and source records attributed to A Theologides.

At least 19 recordsLinked to original sources

Homogeneous trinder-coupled assay for the determination of glucose-6-phosphatase activity in tissue extracts.

We describe an automated, homogeneous, glucose oxidase-coupled method for the determination of glucose-6-phosphatase activity in tissue extracts. The method is based on measurement of the rate of glucose formation by the Trinder reaction, in which the end product is a quinoneimine dye which absorbs maximally at 505 nm and has a molar extinction coefficient of 5700. The incubation mixture contains 20 microL of tissue extract, 25 microL of 0.5 M phosphate buffer, pH 7.0, 175 microL of Trinder/glucose-6-phosphate reagent, and 30 microL of distilled water. After a delay period of 15 min, to exhaust any glucose endogenously present in the extract, glucose production from glucose-6-phosphate is monitored at 505 nm for 5 min in a centrifugal analyzer. The Km was 13 mM over a 10-fold range in glucose-6-phosphate concentration and the reaction was linear up to about 250 U/L. Within-run CV of the assay at activities of 48 and 190 U/L ranged between 2.5-5.0%. The between-run CV at 190 U/L was 5.1%.

Animals

Effect of tumor necrosis factor on enzymes of gluconeogenesis in the rat.

The effect of human recombinant tumor necrosis factor (TNF)-alpha on enzymes of gluconeogenesis in the rat was investigated by determining the activity of glucose 6-phosphatase, fructose 1,6-diphosphatase (FDP), and phosphoenolpyruvate carboxykinase in the liver and kidney of fed and fasted rats. The activity of transaldolase in the pentose phosphate pathway was also measured. Starvation of rats for 24 hr resulted in a 1.6- to 3.1-fold increase in liver and kidney glucose 6-phosphatase and phosphoenolpyruvate carboxykinase (P less than or equal to 0.05), a decrease in liver and kidney FDP (P less than 0.002), and an increase in liver and kidney transaldolase (P = 0.0001). Injection of 50 and 100 micrograms/kg/day of TNF for 5 days resulted in a significant (P less than or equal to 0.03) decrease in kidney FDP only. Injection of 100 micrograms/kg/day of TNF for 5 days with a 24-hr fast on Day 5 resulted in a significant (P = 0.04) increase in liver transaldolase, and a significant decrease in kidney FDP and phosphoenolpyruvate carboxykinase. Comparison of the enzyme activities of rats injected with 100 micrograms/kg/day of TNF for 5 days with those of their pair-fed control partners revealed additionally a significant decrease in glucose 6-phosphatase in the liver (P less than 0.001). It is concluded that TNF administration in the rat has different effects on the enzymes of gluconeogenesis in the liver and kidney, and these effects differ from those seen in starved or tumor-bearing rats.

Animals

Geographic distribution of xanthine oxidase, free radical scavengers, creatine kinase, and lactate dehydrogenase enzyme systems in rat heart and skeletal muscle.

The geographic distribution of the following enzyme systems is described in the rat heart (left and right ventricles) and in different skeletal muscles (soleus, plantaris, and red and white gastrocnemius): xanthine oxidase and dehydrogenase, creatine kinase isoenzymes, lactate dehydrogenase isoenzymes, and the free radical scavenger enzymes superoxide dismutase, glutathione reductase, and glutathione peroxidase. No substantial difference in enzyme activities was observed between the left and right ventricles. Skeletal muscles showed a clear distinction between enzyme activities depending on their composition of oxidative fibers and glycolytic fibers.

Animals

Cancer cachexia.

Cancer cachexia is characterized clinically by anorexia, early satiety, weight loss. anemia, and marked asthenia. The syndrome is not the result of semistarvation alone but it represents a complex metabolic problem. In the host there are abnormalities in metabolism of energy, carbohydrate, lipid and protein, in water content, in acid-base balance, in electrolyte, mineral and vitamin concentrations, alterations in the activity of host tissue enzymes and changes in endocrine homeostasis and immunologic mechanisms. The cancer initiates and contributes to the genesis of the syndrome but complications of the disease and the treatment may also play a role. Only the control of the cancer can reverse completely the syndrome. It was proposed that cancer peptides throw the host metabolism into a chaotic biochemical state by activating and inactivating host enzymes. This results in increased energy expenditure; the released host metabolites and trapped by the growing cancer.

Animals

Combination versus successive single agent chemotherapy in lymphocytic lymphoma.

Fifty-three patients with advanced lymphocytic lymphoma were randomly assigned to treatment with the combination cyclophosphamide, vincristine, and prednisone (CVP) or the same agents used successively in maximal doses (C-V-P). Complete remissions occurred in 68% with CVP and 48% with C-V-P. For patients with nodular lymphoma, the complete remission rate was 81% with CVP and 46% with C-V-P. In patients with diffuse lymphoma a complete remission rate of 50% was obtained with both regimens. The median duration of response was longer for patients who obtained complete remission with CVP (37+ months) than for those entering remission with C-V-P (25+ months). More patients treated with CVP still survive. Current results suggest that CVP is a better induction regime than C-V-P in patients with nodular lymphoma. However, in patients with diffuse lympoocytic lymphoma, neither regimen results in more than 50% complete remissions or significant numbers of prolonged responses. More effective therapy is needed.

Adult

CCNU, vinblastine, and delalutin therapy in renal cell carcinoma.

Advanced renal cell carcinoma is relatively resistant to most adequately evaluated chemotherapeutic agents. The combination of CCNU and vinblastine, which has antitumor activity in a frog renal carcinoma model system, has demonstrated activity in initial studies in man. The current study investigated this combination of drugs together with a progestational agent, Delalutin. Seventeen patients with metastatic renal cell carcinoma were treated with CCNU, vinblastine and Delalutin. There were no objective responses. Four patients with stable disease had a mean survival of 18 months compared to 13 patients with progressive disease who had a mean survival of 5 months. The survival of the four patients with stable disease was in large part due to the slowly progressive natural history of their disease.

Adenocarcinoma

Prolactin dynamics following transphenoidal hypophysectomy for metastatic carcinoma of the breast.

In nine patients who had undergone trans-sphenoidal hypophysectomy, prolactin dynamics were studied with intravenous thyrotropin releasing hormone (TRH). Residual prolactin secretory reserve was demonstrated in seven. Five patients were TRH tested both before and after trans-sphenoidal hypophysectomy. Hypophysectomy did not alter base line prolactin concentration but did decrease prolactin response to TRH from 55 ng/ml to 21 ng/ml (p less than 0.001). Post-hypophysectomy L-Dopa suppressed baseline prolactin concentrations to undetectable levels. There was no correlation between alterations in prolactin dynamics and tumor response to hypophysectomy. Trans-sphenoidal hypophysectomy is not effective in ablating prolactin secretion and serious doubts are raised about the role of altered prolactin dynamics in inducing breast cancer remission.

Breast Neoplasms

Post-hypophysectomy insulin response in patients with advanced breast cancer.

Seven postmenopausal women with metastic breast cancer underwent transsphenoidal hypophysectomy. The rate of disappearance, k*, of iv glucose and insulin following iv glucose and l-arginine infusion was determined before and after the ablation. The k* was estimated with a linear least squares weighted regression method. The insulin secretory capacity of the pancreas before and after the ablation was evaluated with the index of insulinogenic reserve, the index representing the quantity of insulin secreted per unit of glycemic stimulus. Following iv glucose and arginine, there was no significant difference in the mean k* for glucose and insulin, before and after the ablation. The insulinogenic index before was lower than the normal. After hypophysectomy, the index decreased further for the first 30 min following iv glucose. In patients with advanced cancer the index of insulinogenic reserve is lower than normal and is suppressed further by hypophysectomy.

Blood Glucose

Nutritional management of the patient with advanced cancer.

Protein-calorie malnutrition, vitamin and other deficiencies, and weight loss frequently develop in cancer patients. Although there is no evidence that aggressive nutritional management prolongs survival, it may improve the quality of life. Efforts should be made to maintain adequate daily caloric intake with appropriate food selection and with control of complications interfering with nutrition. In selected patients, intravenous hyperalimentation can provide adequate nutrition during potentially effective chemotherapy or radiotherapy. Elemental diets also may be a source of complete or supplemental nutrition. Further experience with both approaches will help to clarify their role in the nutritional management of the patient with advanced cancer.

Anorexia

Hypereosinophilic syndrome with biventricular involvement.

In a 45-year-old man with hypereosinophilic syndrome, cardiac disease, mainly endocardial thickening and extensive mural thrombosis of both ventricles, was confirmed at autopsy. Early in the course of the disease, right ventricular endocardial biopsy had demonstrated the basic process. Restriction in filling and contraction of the right ventricle were demonstrated by functional studies. By echocardiographic study, progressive reduction in size of the right ventricular cavity and premature opening of the pulmonary valve were demonstrated, while this method was less adequate in identifying the process in the left ventricle.

Autopsy

Value of alkaline phosphatase, 5'-nucleotidase, gamma-glutamyltransferase, and glutamate dehydrogenase activity measurements (single and combined) in serum in diagnosis of metastasis to the liver.

We assessed, in 98 patients with cancer, the diagnostic value of measuring serum alkaline phosphatase, 5'-nucleotidase, gamma-glutamyltransferase, and glutamate dehydrogenase activities as an aid to detection of liver metastases. All four enzymes showed diagnostic value, but 5'-nucleotidase appeared to have the greatest. It showed the lowest false-positive results (7.4%) with the highest predictive value of a positive test (85.7%) and agreement (81.3%).. gamma-Glutamyltransferase showed the lowest proportion of false-negative results (2.8%), but was the least specific 35% false-positive results). Analysis of various test combinations showed that the best agreement (77.5%) was obtained when the patients were divided into those who had no or only one abnormal test result, and those who had two or more abnormal test results. However, this was not better than the agreement for 5' nucleotidase alone (81.3%). The agreement of 5'-nucleotidase and gamma-glutamyltransferase (i.e., both tests were positive or negative) was excellent (91.4%), but such agreement included only 67% of the patients with liver metastases.

Alkaline Phosphatase

Cancer cachexia.

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Anemia