Peter Schick

Kinetics of lymphocytes in Hodgkin's disease

SummaryLymphocyte kinetics was studied in 4 patients withHodgkins disease (Stage III A and IV B) by means of a single i. v. injection of3H-thymidine (0.15 μCi/g body weight) and autoradiographic analysis of the labelling pattern of blood and tissue lymphocytes over a period of 7–25 days.The cause of the blood lymphocytopenia in the three lymphopenic patients was the accelerated turnover of the majority of the blood lymphocytes. The average turn-over time of the blood lymphocytes in these patients was about 5 days as compared to 27 days in aHodgkin patient without lymphopenia and to 50 days in non-lymphopenic tumour patients. The turnover times of the small blood lymphocytes were about 14 days in the lymphopenic Hodgkin patients and 70–115 days in hematologically normal patients. Lymphocytopoiesis seemed to be increased in the lymph nodes and in the blood inHodgkins disease. The blood lymphocyte production index was was 61–259 lymphocytes/mm3/day as compared to 40–50 lymphocytes/mm3/day in hematologically normal patients. The generation time of the lymphopoietic cells was estimated to be approximately 24 hours.Our data suggest that the activity of the disease was correlated with accelerated turnover of lymphocytes and increased lymphocytopoiesis.ZusammenfassungBei 4 Patienten mit Lymphogranulomatose (Stadium III A und IV B) wurde die Kinetik von Blut- und Gewebslymphozyten nach einer Einzelinjektion von3H-Thymidin autoradiographisch untersucht.Bei den 3 lymphopenischen Patienten war die Lymphopenie des Blutes durch einen gesteigerten Umsatz der Blutlymphozyten bedingt. Die mittlere Umsatzzeit der Blutlymphozyten betrug bei diesen Patienten 5 Tage, verglichen mit einer mittleren Umsatzzeit von 27 Tagen bei einem Lymphogranulom-Patienten ohne Lymphopenie und von etwa 50 Tagen bei nicht-lymphopenischen Tumorpatienten. Die mittlere Umsatzzeit der kleinen Blutlymphozyten wurde bei den lymphopenischen Lymphogranulomatose-Patienten mit 14 Tagen und bei nicht-lymphopenischen Tumorpatienten mit 70–115 Tagen berechnet. Die Lymphozytopoese bei den Lymphogranulomatose-Patienten war erhöht. Das galt gleichermaßen für die vergrößerten Lymphknoten und das Blut. Der Blutlymphozyten-Produktionsindex betrug 61-259 Lymphozyten/mm3/Tag im Vergleich zu 40–50 Lymphozyten/mm3/Tag bei hämatologisch normalen Patienten. Die Generationszeit der lymphopoetischen Zellen ließ sich auf 24 Stunden schätzen.Die Befunde weisen darauf hin, daß bei der Lymphogranulomatose die Aktivität des Krankheitsprozesses mit gesteigertem Lymphozytenumsatz und stimulierter Lymphozytopoese korreliert ist.

Kinetic differences of autotransfused 3H-cytidine labeled blood lymphocytes in leukemic and non-leukemic lymphoma patients☆

After in vitro incubation with 3H-cytidine, labe led blood lymphocytes were autotransfused in 2 hematologically normal persons, 6 patients with chronic lymphocytic leukemia (CLL) and 3 non-leukemic patients with malignant lymphomas, 2 with lymphosarcoma (LSA) and 1 with reticulum cell sarcoma (RSA). Five minutes after completion of autotransfusion labeling indices were found to be 3–5% in the CLL-patients, 3% in the RSA-patient, 2% in the 2 hematologically normal patients and about 1% in both patients with LSA. From these indices and their extrapolation to zero time it is deduced that the lymphocytes distributed themselves within minutes into a “space” 1·7 to 8 times larger than the “circulating lymphocyte pool (CLP)” calculated on the basis of blood lymphocyte concentration multiplied with the blood volume. During the first hour after autotransfusion, the labeling index of the blood lymphocytes decreased until a plateau was reached. The level of this plateau was found to be between 0·2% and 0·6% in the non-leukemic and between 1·8% and 3·6% in the leukemic patients. At this time labeled lymphocytes were found in lymph node sections and bone marrow smears presumably outside the blood vessels. Therefore, the autotransfused lymphocytes distributed themselves within 1 to 2 hr into a “rapidly exchangeable lymphocyte pool (RELP)” containing intra- and extravascular subpools. The RELP/CLP ratio ranged between 2·5 and 5·7 for the 6 CLL-patients. It was 6·2 and 19 for the 2 hematologically normal patients, 14 for the RSA-patient and 46 and 51 for the 2 LSA-patients. The findings indicate that the method of autotransfusion of 3H-cytidine labeled lymphocytes is suitable to determine the ratio between a circulating and a rapidly exchangeable lymphocyte pool. They suggest that lymphocytes from CLL-patients exchange only poorly with extravascular lymphocyte pools, while this exchange seems normal or even increased in patients with the diagnosis of LSA and RSA.

DNA-synthesizing T and non-T cells in chronic lymphocytic leukemia

ZusammenfassungBei 21 Patienten mit chronischer lymphatischer LeukÄmie (CLL) und 8 Normalpersonen wurde die Anzahl der DNA-synthetisierenden peripheren Blutlymphozyten autoradiografisch untersucht. Die Lymphozyten wurden dabei mit Hilfe des EN-Rosettentests in T-Zellen und Nicht-T-Zellen differenziert. Es zeigt sich eine normale T-Zellproliferation und eine erhöhte Nicht-T-Zellproliferation im Stadium O-I. In den fortgeschritteneren Krankheitsstadien erfÄhrt die Proliferation für T- und Nicht-T-Lymphozyten eine signifikante Steigerung. Die Proliferation der T-Zellen ist im Stadium IV auf das ca. 20fache, die der Nicht-T-Zellen auf das ca. 50fache gesteigert. Auf die Möglichkeit zu prognostischen Aussagen wird hingewiesen.SummaryIn 21 patients with chronic lymphocytic leukemia (CLL) and in 8 hematologically normal persons the number of DNA-synthesizing peripheral blood lymphocytes was investigated by autoradiographic techniques. The lymphocytes were differentiated by En-rosette tests into T and non-T lymphoid cells. The results show a normal number of proliferating T lymphoid cells and an increased number of proliferating non-T lymphoid cells in clinical stages O-I. Stages III–IV demonstrate a significant increase of the proliferation rate of both T and non-T lymphoid cells. The possible pathogenetic factors and the prognostic value of these results are discussed.

Morphologische und funktionelle Veränderungen im Blutzellsystem des Meerschweinchens nach Behandlung mit cytostatischen Substanzen, Prednisolon und Phenylbutazon

SummaryGuinea pigs, having developed cutaneous tuberculin hypersensitivity after immunization with BCG were treated for 10 days by intraperitoneal injections of moderately toxic doses of cyclophosphamide, triethylene melamine, ibenzmethyzin, 6-MP, amethopterin (6 injections in 13 days), actinomycin C, vinblastine, podophyllin derivative, prednisolone and phenylbutazone. After 5 days of treatment tuberculin reaction was suppressed in most animals by 6-MP, whereas the other substances had only moderate or no effect. After 10 days of treatment, however, tuberculin reactions were markedly diminished by nearly all applied substances with exception of vinblastine, TEM and amethopterin, which caused only weak effects. Inspite of nearly complete inhibition of the tuberculin reaction at the end of treatment with 6-MP and ibenzmethyzin a state of tolerance never developed. There was a correlation between the intensity of tuberculin reaction and the number of small lymphocytes with a pale cytoplasm in the blood. An unspecific inflammation, Rebucks skin window (like the tuberculin reaction characterized by an intensive mononuclear cell infiltration), caused simultaneously with the tuberculin reaction immediately after the period of treatment was more or less markedly diminished by 6-MP, TEM, cyclophosphamide, ibenzmethyzin, podophyllin derivative and actinomycin. The notably good inhibition of an immunological reaction of the delayed type by a large scale of different substances in our experiments is explained by an immunosuppressive effect of all and an anti-inflammatory effect of some substances and by some kind of immunoparalysis caused by frequent injections of antigen.

Factor VIII coagulant activity and factor Vlll-related antigen released from isolated perfused human spleens

SummaryEight human spleens were perfused for up to 65 h at normothermia and the coagulant Factor VIII activity measured in the perfusate. In addition, in three experiments Factor VIII-related antigen was determined in the perfusate. Although the spleens were pathologically enlarged and the normal structure involved by different diseases, all spleens released Factor VIII coagulant activity and Factor VIII-related antigen. On average the total amount of Factor VIII coagulant activity released was equivalent to that of 3.5 1 of human plasma.ZusammenfassungBei der normothermen Langzeitperfusion von 8 menschlichen Milzen wurde ein Anstieg des Gerinnungsfaktors VIII im Perfusat gemessen und in 3 FÄllen die Konzentration des Faktor VIII-assoziierten Antigens bestimmt. Obwohl es sich um pathologisch verÄnderte Milzen handelte, stieg in allen FÄllen die Faktor-VIII-AktivitÄt und die Konzentration des Faktor-VIII-assoziierten Antigens an. Der Mittelwert des maximalen Gehalts an Faktor VIII entsprach der GerinnungsaktivitÄt von 3,5 1 menschlichen Plasmas.