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Biomedical subjects

C M Ambrus

Publications and source records attributed to C M Ambrus.

At least 55 records · Page 3Linked to original sources
PubMed1982

Depletion of phenylalanine in the blood of phenylketonuric patients using a PAL-enzyme reactor. An in vitro study.

Blood samples obtained from eight adult phenylketonuric individuals had a mean phenylalanine level of 25 mg/dl. When these samples were circulated through multitubular enzyme-reactors prepared with immobilized phenylalanine ammonia lyase an average of 77% of phenylalanine was metabolized within 30 minutes. We conclude that phenylalanine in human phenylketonuric blood is just as susceptible to metabolism by PAL-enzyme reactors as phenylalanine that is added to normal blood, or that is circulating in dogs and monkeys made hyperphenylalaninemic by experimental means.

Adult↗
PubMed1981

Cyclic nucleotide phosphodiesterases in normal and malignant human tissues.

Biopsy samples were obtained from tumor tissue and surrounding normal tissue from the same organs of the same patients in 25 patients. Adequate studies could be performed on all parameters in 18 tissue pairs: 12 malignant melanomas, 4 sarcomas, and 2 others. Significantly higher levels of cAMP low affinity phosphodiesterases were found in the tumors as compared to the controls. Similar differences were seen in the high affinity cAMP phosphodiesterases, but these were of borderline significance. High affinity cGMP phosphodiesterase levels did not differ significantly between normal and neoplastic tissue samples. Low affinity cGMP phosphodiesterases were not detectable in either tissues. These studies together with earlier experimental findings suggest possible auxiliary therapeutic trials with phosphodiesterase inhibitors.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1981

Burkitt's lymphoma.

Clinical and epidemiologic features of Burkitt's lymphoma are reviewed. Epidemiologic studies suggest that simultaneous infection with Epstein-Barr (E-B) virus and malaria may be involved as etiologic agents. On the other hand we have found that in the Amazon region of Brazil and Peru both malaria and E-B virus infection is common among children, yet Burkitt's lymphoma is rare. The possibility exists that other concomitant etiologic agents and genetic factors are also involved. Several investigators suggested the possible involvement of Reo 3 virus. We have found antibodies against Yaba virus. A laboratory worker who accidentally inoculated himself with Yaba virus developed a histiocytoma which when inoculated into Asiatic monkeys produced typical Yaba tumors. This was the first case that Koch's postulates were fulfilled in a virus induced neoplasm in man. Therapeutically, the best clinical results were obtained in those patients who were treated with small doses of cyclophosphamide. On the basis of somewhat inadequate follow-up studies, it is estimated that "five year cures" were obtained in about 10% of the patients.

Adolescent↗
PubMed1981

Effect of phosphodiesterase inhibitors on platelet aggregation and tumor metastasis.

Recent studies suggest a relationship of platelet aggregation to metastatic spread of neoplasia. In the present experiment pentoxifylline appears to be a highly effective platelet aggregation inhibitor: a dose-response curve is apparent in monkey between 6 and 24 mg/kg i.v. Besides pentoxifylline significantly reduces metastasis rates in Wilms' tumor and neuroblastoma in rodents: 18 mg/kg significantly increase polyploid Ehrlich ascites tumor cell circulation time; on the contrary it has no effect on metastasis in the NIH renal adenocarcinoma. It is thus possible that platelet factor related blood coagulation processes play a different role in the fate of these tumor cells. This may be related to cell membrane characteristics. Phosphodiesterase inhibitors alter membrane fluidity and cell deformability of cancer cells which may pass the microcirculation easier and are less likely to settle and form metastases. Agents with both platelet aggregation inhibitory and red cell deformability increasing effect may find a place in our therapeutic armamentarium in oncology.

Adenocarcinoma↗
PubMed1981

Development of a refractory stage in a dog model for phenylketonuria.

Dogs were fed a continuous diet of phenylalanine (Phe) daily and para-chloro-phenylalanine (p-CPhe), an inhibitor of phenylalanine hydroxylase (PH-ase) every second day. It was reported that such a diet produces a sustained hyperphenylalanemia in rats. We have found, however, that in dogs an initial rise in circulating Phe is followed, after a period of time, by a return to normal levels in spite of diet maintenance. PH-ase ws measured in liver samples obtained from dogs before the start of the above diet and at the time when Phe levels returned to normal. It was found that the post-feeding liver sample had 57%-100% less activity than the normal sample. Accordingly, decline in Phe levels cannot be attributed to an increase in PH-ase activity. Experiments are being initiated using labelled Phe, to investigate whether chronic feeding of Phe and p-CPhe resulted in an intestinal block to Phe absorption, which may explain our experimental findings.

Animals↗
PubMed1980

Radiation sensitizing agents in clinical radiation and chemotherapy.

Patients with bronchogenic carcinoma or with advanced pediatric solid tumours were treated with various radiation therapy schedules alone or with a new alkylating carbamate: AB 132. Drug therapy appeared to potentiate radiation therapy results without significant toxicity except for certain neurologic symptoms (myasthenia, nightmares, disturbances of taste and smell). The latter appeared to be related to acetylcholinesterase and pseudocholinesterase inhibition.

Aziridines↗
PubMed1980

Multitubular reactors with immobilized L-phenylalanine ammonia-lyase for use in extracorporeal shunts.

Hollow fiber cartridges of improved design have been loaded with L-phenylalanine ammonia-lyase [EC 4.3.1.5.] from Rhodotorula glutinis in order to prepare multitubular enzyme reactors for removal of L-phenylalanine from blood. The kinetics of the enzyme in free solution was investigated and the results showed a behavior similar to that reported for L-phenylalanine ammonia-lyase from other sources. On the other hand kinetic data with the reactors were obtained in a recirculating system by measuring the increase in trans-cinnamate concentration in the perfusate. The effect of changing the enzyme load in the hollow fiber cartridge, the length of the cartridge, the substrate concentration, pH as well as the flow rate and the temperature have been investigated. The results showed that the overall kinetics of the enzymic reaction in the multitubular reactor is not the same as that in free solution and the difference can be attributed to diffusion resistances in the hollow fiber system.

Ammonia-Lyases↗
PubMed1979

Inhibitors of fibrinolysis in diabetic children, mothers, and their newborn.

Late diabetic complications are often related to vascular changes and formation of thrombi in the altered vasculature. Contributing factors to thrombosis susceptibility of diabetic patients include changes in clotting factors, platelets, and inhibition of fibrinolysis. We have measured various fibrinolytic inhibitors in the blood of diabetic children, diabetic pregnant women and their offspring, and healthy controls. Inhibitors studied included 1) fast (immediate) antiplasmin, 2) slow (progressive) antiplasmin, 3) alpha-2-macroglobulin, and 4) alpha-1-antitrypsin. It appears from our study that high fast-antiplasmin levels, and low or missing slow-antiplasmin levels are characteristic of diabetic patients and of newborn of diabetic mothers. The reason for high fast-antiplasmin levels is not clear: Levels are not connected with the age of the patient or duration of diabetes, and are not elevated in response to a fibrinolytic process (fibrin decomposition products could not be shown to be present in the serum of diabetic children). Alpha-2-macroglobulin was significantly higher and alpha-1-antitrypsin significantly lower in diabetic women than in controls. In the other groups of patients studied differences in these inhibitors from the appropriate control groups were not statistically significant.

Adolescent↗
PubMed1979

The fibrinolysin system and its relationship to disease in the newborn.

The fibrinolysin system is incomplete in newborn infants. Lack of serum plasminogen in premature newborn has an important role in the pathophysiology of the respiratory distress syndrome since alveolar fibrin deposits cannot be eliminated. Urokinase activated human plasmin has increased the survival rate of infants with respiratory distress syndrome. Plasminogen given I.V. at birth has reduced the incidence and the severity of respiratory distress syndrome, in a randomized double-blind study of 500 premature infants. Death in the plasminogen recipient group occurred only among infants born to mothers with bleeding complications of pregnancy. Plasmin inhibitors measured with a functional assay were the highest in this group of infants, serum plasminogen was the lowest; when activator and purified human plasminogen were added to the serum, fibrinolytic activity was elicited in excess of the plasminogen added. It is suggested that plasminogen and/or plasmin inhibitors may be abnormal fetal variants in infants born to mothers with bleeding complications.

Clinical Trials as Topic↗
PubMed1979

Mechanism of action of fibrinolytic enzymes in vivo.

Plasminogen-rich and plasminogen-poor radiolabeled human fibrin clots were inserted into large veins of baboons and stump-tailed monkeys. The thrombolytic effects of plasminogen activators (urokinase, streptokinase), and plasmin preparations with activator activity (streptokinase-activated human plasmin) and without activator activity (trypsin-activated porcine plasmin, Lysofibrin) were studied. Plasminogen-free and plasminogen-rich clots lysed at equal rates. Preparations with and without activator activity were equally effective as thrombolytic agents. Endogenous activation of plasminogen in the clot thus appears not to be the essential mechanism of thrombolysis. The exogenous pathway of enzyme adsorption to fibrin fibers seems to represent an important thrombolytic mechanism. Clot lysis was achieved with doses of fibrinolytic enzymes which produced little or no significant hematologic changes including hypofibrinogenemia and decreases of other blood coagulation factor levels.

Animals↗
PubMed1979

Studies on vasoocclusive crisis of sickle cell disease. I. Effect of pentoxifylline.

A method was developed to induce and continuously monitor vasoocclusive crisis of sickle cell disease in non-human primates. Pentoxifylline, a phosphodiesterase inhibitory agent, showed significant preventive effect. This may be based on its ability to increase intracellular cAMP levels and consequently to decrease platelet aggregation and to increase red cell deformability.

Anemia, Sickle Cell↗
PubMed1979

The biphasic nature and temperature dependence of the activation of human plasminogen by urokinase. A simple urokinase assay based on this phenomenon.

Activation of plasminogen is a biphasic process, the first phase is temperature independent, the second phase is not. The first phase of activation is completed immediately when urokinase (UK) is combined with plasminogen. At 4 degrees C the fibrinolytic activity generated in the first phase is directly proportional to the concentration of UK used for activation. This linear relationship permits the construction of a standard curve for the quantitative measurement of UK in samples with unknown concentrations of UK. The second, slower phase of activation follows the first only at higher temperatures (e.g. 28 degrees C), is limited by the plasminogen concentration, and is completed within 30 minutes of incubations. Activation of plasminogen by streptokinase under the same conditions follows a different pattern.

Biological Assay↗
PubMed1978

Phenylalanine depletion for the management of phenylketonuria: use of enzyme reactors with immobilized enzymes.

Multitubular enzyme reactors with immobilized phenylalanine ammonia lyase were tested in vitro and in vivo for depletion of phenylalanine in circulating blood. Sustained reduction of phenylalanine was achieved in less than 30 minutes. A 50% decrease of phenylalanine was obtained with a 2-hour application of enzyme reactors and was maintained for more than 2 days. Similar enzyme reactors have therapeutic potential for temporary management of phenylketonuric patients when their circulating phenylalanine becomes exceedingly high because of infection, fever, or pregnancy.

Ammonia-Lyases↗