Results of a randomized trial of prophylactic chemotherapy in T3-T4 breast cancer patients previously treated by radiotherapy.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to R Plagne.
Explore the source record for details and available documents.
1. The absorption, distribution and elimination of a new alkylating agent, N,N-bis(2'-chloroethyl)4-amino-2-methyl-1-methoxynaphthalene (mitoclomine), labelled with 14C either in the dichloroethyl group or in the methoxy group, have been studied in mice and rats. 2. Expired 14CO2 of rats given [chloroethyl-14C[- or [methoxy-14C]mitoclomine amounted to 1.0 and 35% dose respectively, indicating that O-dealkylation occurs. 3. The part of the molecule carrying the cytotoxic group displayed a high affinity for lymphoid organs (thymus, spleen). This could explain some biological properties of this drug, especially the selective effects of mitoclomine on circulating lymphocytes.
The preparative electrophoretic method allows separation of several cell populations, which can be characterized by the usual membrane markers. This qualitative study shows a heterogeneous distribution of the T-lymphocytes from the most rapid to the slowest migration zones. The electrophoretic mobility (E.M.) of each fraction has been studied by analytical electrophoresis, which confirms the heterogeneity of T-cells. The experiments used total blood lymphocytes and rosette-forming cells with sheep red blood cells. The results obtained with the two methods were well correlated. The average migration speed of the separated populations showed a regular variation from one extreme fraction to the other. The E.M. speeds that characterize the main populations are--0.90 micrometer.sec.--1v.--1cm for the B-lymphocytes; for the T-lymphocytes,--1.10 (previously identified as the "low affinity" E-rosette FC),--1.20 and a small population centered around--1.35 (corresponding to active E rosette FC). In the T-lymphocytes separated after E-rosetting, the progresssive variation in the mean E.M. of each fraction is confirmed, as well as the existence of the previous 3 T-cell populations. Further studies have to be done, to show that each separated population does correspond with a functional differentiation.
The electrophoretic mobility of circulating lymphocytes has been studied in normal human subjects after immunization by tetanus toxoid. The mean migration speed was shown to increase, particularly two and three days after secondary immunization. This increase appeared to be due to the elevation of percentage of T cells migrating at 1.20 and 1.35 micrometer. sec.-1v.-1 cm. (active rosettes-forming cells), with a decrease of the percentage of B cells and T lymphocytes migrating at 1.10 micrometer. sec.-1v.-1 cm. The return to the anterior status was observed between day 4 and 8 after immunization.
Clinical findings in cancer patients and experimental results after separation of active rosettes-forming cells are compatible with the hypothesis that the lymphocytes which do form active rosettes are those whose electrophoretic mobility is about 1.20 micron. sec-1v.-1.cm.
Cell surface charge, assessed by the analytical electrophoresis of fresh and cryopreserved human peripheral blood lymphoctes, is changed in any perceivable manner by freezing and thawing. This was confirmed by different membrane markers (E, EA and EAC rosettes).
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Cell electrophoresis allows separation of normal human lymphocytes into two principal groups which are a function of their relative rates of migration. In 42 healthy adults, 19.9% of the lymphocytes have a slower migration rate, and 80.1%, a faster migration rate than the reference speed (1 mum - sec-1 - cm). Two methods are used for the selection of the lymphocytic populations: spontaneous rosetting with sheeps red blood cells, a property of T-lymphocytes, and adherence to nylon wool columns, which preferentially selects B-lymphocytes. The cells which do not form spontaneous rosettes, but adhere to nylon wool columns show mainly slow migration. Cells which do not adhere to nylon columns show a faster migration rate. These findings affirm the T-nature of the rapidly migrating lymphocytes, and the B-nature of the slow-migrating lymphocytes. Results by the immunofluorescence technique confirm this.
Cell electrophoresis enables the separation of the lymphocytes in normal human blood into two principal groups, as a function of their migration speed in relation to 1 mum.sec -1..v-1.cm. In 42 healthy adults, 19,9 % of the lymphocytes have a slower migration, and 80,1 % a faster migration than the reference speed. Two known methods are used for the selection of the lymphocytic populations : spontaneous rosetting with sheep red blood cells, a property of the T lymphocytes, and the adherence to nylon wool columns, which is dominant in the case of B lymphocytes. The cells which do not form spontaneous rosettes, and the cells adhering to nylon wool columns have above all a slow migration. On the contrary, cells which do not adhere to nylon columns have a fast migration. These arguments are in favour of the T nature of the rapid migrating lymphocytes, and of the B nature of the slow migrating lymphocytes.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Determination of electrophoretic mobility of lymphocytes in 70 cancer patients shows a significant decrease of the fast moving cells. It seems to be a relation between the percentage or absolute number of the rapid lymphocytes and dissemination and prognosis of the disease. This decrease is in agreement with the variations of the T lymphocyte population described in cancer patients with other methods. On the contrary, although there is reduction of total blood lymphocytes, the number of slow moving cells is not reduced. The changes observed in mean migration speed of fast and slow migrating lymphocytes could indicate more selective alterations in some cell subpopulations.
A simple, rapid histone agglutination test (HAT) is described. It consists of incubation in microplates or in microtubes of blood lymphocytes isolated from cancer patients and patients with non-malignant diseases with microquantities of histone fraction F2A1. Positive reaction is shown by massive agglutination of lymphocytes of the patients tested (126 subjects): this test was positive in 76% of cases. All controls (59 subjects) were negative.
Mode of action of chlorambucil first metabolic studies by means of carbon-14 labelled isotpoes rheumatological implications of the results. Chlorambucil, gamma [rho-di(2-chloroethyl) aminophenyl] butyric acid, was labelled in either the carboxylic group (Ia), the mustard radical (Ib), or the carbon atom in the aplha position in the carboxylic group (Ic). The first studies by total autoradiography of mice, by organ fixation, by analysis of urine, faeces, and expired air of rats, and by microautoradiography of sections of organs and smears of tissues from rats and rabbits produced the following results: the metabolism of chlorambucil includes a long hepatic time; the molecule undergoes beta-oxidation almost certainly in the liver; thenthe oxidized form become localized in two potential target organs: the thymus and the bone marrow; there is no elective fixation in normal joints of any ot the three labelled compound studied; on the other hand, with all three molecules, there was elimination via the bile ducts, slight movement into the thoracic canal, and labeling ofHarder's glands (particularly with Ia and Ic); elimination of the three compounds in urine was complex. These facts suggest that chlorambucil undergoses activation in the liver, in the same way as cyclophosphamide; however, the similarity end there. The other steps in metabolism give rise to different molecules for these compounds. The high concentrations of chlorambucil in the thymus and the labelling of the marrow cells indicate that the action of this cytostatic compound is primarily immunodepressive.
86Rb has been used as a tracer for Sarcoma 180 ascitic cells in a humoral cytotoxicity system, and compared with the trypan blue dye exclusion method. In as little as five minutes after contact with antiserum and complement, about 90 p. cent of the isotope has gone from the cells, with a significant difference between controls and experimentals. There is a good correlation between 86Rb and trypan blue dye exclusion results. The only pitfall is a relative fragility of cells during the centrifugation stages of the two washings.
Cell electrophoresis allows separation of normal human blood lymphocytes into two main groups which are a function of their relative rates of migration, with regard to the reference speed (1 mum.sec.-1V-1.cm): the lymphocytes which have a greater mobility than this value seem to be T-lymphocytes (80,1 per cent for 42 healthy adults); on the contrary, B-lymphocytes have an inferior mobility (19,9 per cent). Two known methods are used for the selection of the lymphoid populations: spontaneous rosetting with sheep's red blood cells, which are characteristic of T lymphocytes, and adherence to nylon wool columns, which is dominant in the case of B-lymphocytes. This method confirms the fact that T-lymphocytes have a rapid migration and B-lymphocytes a slow migration. We have isolated a third population, having neither the T markers, nor the B markers. It has a very homogeneous migration, centered on the two classes 1,05 and 1,10 mum.sec.-1.V.-1.cm.
Explore the source record for details and available documents.