Gerhard Weissbach

Release of adenosine triphosphate by adenosine diphosphate in whole blood and in erythrocyte suspensions.

In whole blood samples from thrombocytopenic patients, large amounts of ATP were released by ADP, exceeding the level obtained with samples from normal persons by far. Because we suspected that the high potential of ATP in erythrocytes would be the main source for this phenomenon, the release of ATP by ADP was measured in whole blood samples from normal, thrombocytopenic, and leukocytopenic persons and in suspensions of washed erythrocytes. The release was recorded by a Whole Blood Lumi‐Aggregometer type 500 VS (Chrono‐Log Corporation, Havertown, PA) using the luciferin‐luciferase system. Not only in samples from thrombocytopenic persons but also with normal platelet count, increasing amounts of ATP were released with increasing ADP concentrations, finally exceeding the ATP releasable from thrombocytes by thrombin. The amounts of ADP required to match the ATP release of thrombin were closely correlated with the platelet counts in the samples. With lower platelet counts, the release mechanism from erythrocytes could be stimulated more easily by low concentrations of ADP. The binding of ADP to platelets occurred with ostensibly higher affinity. The phenomenon of overshooting ATP release was also observed in samples from extremely leukocytopenic patients. A very large release of ATP was also achieved in suspensions of washed erythrocytes. In this way our hypothesis of ATP release from erythrocytes by ADP was confirmed again. The mechanism of the release from erythrocytes remains unclear. We speculate that its purpose is to regulate extracellular nucleotides in the circulating blood. Am. J. Hematol. 56:259–265, 1997.

Non-Hodgkin lymphoma (NHL) as a second neoplasm occurring after neuroblastoma treatment

As far as we know, this is the first report of a non-Hodgkin lymphoma developing after successful treatment of neuroblastoma. A boy was found to have a mediastinal T-cell lymphoma at the age of 5. He had been treated for a neuroblastoma of the left adrenal region 4 years before, when by intensive chemotherapy and radiation a complete remission of the primary tumor was achieved. The second malignancy has also been controlled without evidence of recurrence 1 year after termination of treatment. We conclude that treatment of a neuroblastoma by cytostatic drugs and radiation may lead to a non-Hodgkin lymphoma as a second malignancy.

CRITICAL EVALUATION OF THE QUANTIFICATION OF ATP RELEASE REACTION IN WHOLE BLOOD

The influence of erythrocyte and thrombocyte content on the release of adenosine triphosphate (ATP) in whole blood was tested. Citrated blood from 39 healthy persons was diluted gradually. The release reaction was induced by arachidonic acid (1.25 mM), adenosine diphosphate (ADP; 30 microM) and collagen (1.0 and 5.0 micrograms/ml). The peak of the obtained curves was transformed into percent values of the maximal deflection by the undiluted sample (PEAK IN RELATION) and into ATP concentrations (ABSOLUTE PEAK). By rising dilution an increase of the peak in relation with all inducers was observed which was mainly due to the luminescence-optical effect. As expected the absolute peak decreased but only under arachidonic acid and collagen. Under ADP despite of the rising dilution constant amounts of ATP were released suggesting an additional release from other blood cells. High ATP release curves in response to ADP were observed in patients with pancytopenia and with thrombocytopenia when compared to health persons. ADP seems not to be suited for the measurement of ATP release reaction in whole blood. Collagen at a final concentration of 1.0 micrograms/ml was found as the optimal inducer. The ATP standard is essential for the quantification of release reaction.

Non‐Hodgkin lymphoma (NHL) as a second neoplasm occurring after neuroblastoma treatment

As far as we know, this is the first report of a non-Hodgkin lymphoma developing after successful treatment of neuroblastoma. A boy was found to have a mediastinal T-cell lymphoma at the age of 5. He had been treated for a neuroblastoma of the left adrenal region 4 years before, when by intensive chemotherapy and radiation a complete remission of the primary tumor was achieved. The second malignancy has also been controlled without evidence of recurrence 1 year after termination of treatment. We conclude that treatment of a neuroblastoma by cytostatic drugs and radiation may lead to a non-Hodgkin lymphoma as a second malignancy.

Endothelin-1 as One of the Mediators of the Interaction between Endothelium and Platelets in Humans

Endothelin-1 (ET-1) is an endothelium-derived peptide with multiple functions affecting the cardiovascular, renal, neuroendocrine, pulmonary and gastrointestinal system1,2. Elevated plasma levels of ET-1 were found in diseases associated with the activation of platelets, e.g. myocardial infarction, disseminated intravascular coagulation and diabetes. These findings prompted us to investigate the ET-1 effect on platelet aggregation in human whole blood and in platelet rich plasma (PRP).