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Biomedical subjects

M Gosalvez

Publications and source records attributed to M Gosalvez.

17 recordsLinked to original sources
PubMed1978

Metabolic control of glycolysis in normal and tumor permeabilized cells.

Our previous reports have presented evidence suggesting the existence in tumor cells of a second control site of glycolysis of pyruvate kinase as a competition for adenosine diphosphate between this enzyme and mitochondria, which is responsible for the Crabtree effect. Now, by using cells partially permeabilized to nucleotides and phosphorylated substrates, we provide evidence supporting the existence in hepatocytes of a partial control by adenosine triphosphate at phosphofructokinase, which is followed by the total control by adenosine triphosphate at pyruvate kinase. The partial or nonoperation of this second site in Ehrlich ascites tumor cells appears to be the cause for the characteristic aerobic glycolysis, Crabtree effect, and low Pasteur effect of these cells.

Adenosine Monophosphate↗
PubMed1978

Phase I clinical study of quelamycin.

A phase I clinical study was done with quelamycin, a recently synthesized triferric derivative of adriamycin. Twenty-one good-risk patients were studied: 19 patients with non-small cell carcinoma of the lung and two patients with metastatic sarcoma. Acute toxicity occurred in all patients and consisted of high fever, flushing, hypertension, generalized body aches, tremors, and confusion, which lasted 3-6 hours. Potentially dangerous cardiotoxicity occurred in eight patients who had previous minor rhythm disturbances, and was characterized by tachycardia, atrial extrasystoles, atrial fibrillation, and branch block which lasted 6-14 hours. The dose-limiting hematologic toxicity was found to occur at 125 mg/m2 iv single-dose. Objective responses were observed in three of 19 patients with lung cancer and in one patient with metastatic osteogenic sarcoma resistant to adriamycin therapy. In conclusion, quelamycin is a new derivative of adriamycin with potential interest. However, the acute generalized toxicity and the immediate cardiotoxicity found in the presently used schedule are excessive. Further studies directed to suppress these side effects are in progress.

Adolescent↗
PubMed1976

Injurious effect on rat liver mitochondria by lymphocytes from patients with primary biliary cirrhosis.

Lymphocytes from primary biliary cirrhosis (PBC) patients were shown to have an injurious effect on rat liver mitochondria, as was demonstrated by the inhibition of mitochondrial respiratory control by these cells. The incubation of the PBC patients' lymphocytes with isolated rat liver mitochondria produced a significant inhibition of mitochondrial respiration in the presence of ADP. However, no significant effect on respiration was seen with control lymphocytes of normal persons or with lymphocytes from patients with alcoholic cirrhosis and miscellaneous liver diseases. The results suggest that this injurious effect of PBC lymphocytes on mitochondria might be a consequence of sensitization in vivo of the PBC patients' lymphocytes by the mitochondrial antigens.

Animals↗
PubMed1975

Stimulation of tumor-cell respiration by inhibitors of pyruvate kinase.

In a model system consisting of highly coupled rat liver mitochondria respiring in the presence of substrate, pyruvate kinase, phosphoenolpyruvate, ATP, hexokinase and glucose, the increase in the mitochondrial concentration results in a progressive decrease in the activity of pyruvate kinase. These results are in accord with a role of pyruvate kinase as a determinant of glycolytic activity by competing with mitochondrial oxidative phosphorylation for the available ADP. The addition of adequate amounts of the amino acids, cysteine, alanine and phenylalanine, known as inhibitors of pyruvate kinase, to living Ehrlich ascites tumor cell suspensions results in a stimulation of the respiratory rate and in a decrease of the glycolytic rate of the cells. Concomitant with these changes, there is an accumulation of intracellular phosphoenolpyruvate and ADP, and a decrease in pyruvate and ATP. These results provide additional evidence for paying attention to pyruvate kinase as another key enzyme whose properties and activities may be major determinants for the control of glycolysis and the Crabtree and Pasteur effects of tumor cells.

Amino Acids↗
PubMed1975

Impairment of mitochondrial respiratory control by activated lymphocytes.

Mitochondria isolated from rat livers were used as a source of antigens capable of producing in vitro activation of lymphocytes that had previously been sensitized in vivo with the same antigen. Such lymphocytes were shown to have an injurious effect on target mitochondria, as was demonstrated by a new biochemical approach based on the study of the inhibition by these cells of mitochondrial respiratory control. A somewhat milder injurious capacity was also observed in normal and sensitized lymphocytes activated in vitro with the mitogen PHA. The lateration of the respiratory control of mitochondria by lymphocytes correlated with an increase in DNA synthesis in these cells.

Adenosine Diphosphate↗
PubMedDate not supplied

Anoxic cardiac arrest: Its effect on myocardial mitochondrial metabolism.

Forty eight healthy dogs are subjects to cardiopulmonary bypass and divide into two groups according to whether the perfusion is performed in normothermia or moderate hypothermia (30 degrees C). The effects on oxidative phosphorylation and mitochondrial respiration, produced by increasing periods of myocardial anoxia from aortic cross clamping, are studied. A clear correlation is found between the disturbances of mitochondrial metabolism and the future cardiac recovery. Hypothermia shows a protective effect on the anoxic myocardium. It is concluded that the period of absolute safety in cardiac anoxia, as far as mitochondrial function is concerned, is 15 minutes in normal thermic perfusion and 90 minutes in moderately hypothermic ones.

Animals↗