Effect of oral self-administration of cocaine on adrenal catecholamine levels and cardiovascular parameters in the conscious rat.
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Biomedical subjects
Publications and source records attributed to B Lau.
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Nalm 6M1 cells, derived from an acute lymphoblastic leukemia of the non-T, non-B type, are known to possess characteristics of early B-lymphocytes. In order to determine whether these cells are able to differentiate along the granulocyte-monocyte pathway, they were cultured in diffusion chambers, and classified according to morphological, cytochemical and immunological criteria. On the basis of this characterization, Nalm 6M1 cells positively labeling with monoclonal anti-human granulocyte or monocyte-specific antibodies were observed in all cases. These immunological changes were accompanied by the appearance of cells positive for the naphthyl-AS-D-chloroacetate esterase reaction. However, no changes in the blast-like appearance of the cultured cells were seen. From these data, we conclude that Nalm 6M1 cells already committed to the B-cell lineage retain their capacity to develop cellular markers of the granulocyte-monocyte series.
Eighteen pretreatment cases of acute lymphoblastic leukemia (ALL) in children were investigated by quantitative autoradiography in order to determine the labeling index (LI) as well as the DNA synthesis time (ts). The ploidy of the leukemic blasts was evaluated by Feulgen-microphotometry. The group consisted of 12 cases expressing the common ALL (CALL) antigen only, while 6 showed varying degrees of development along the T-cell axis. The latter subgroup was taken together and termed T-ALL for the sake of simplicity. By dividing LI by ts the fractional birth rate (FBR) was derived representing the percentage of the total leukemic cell mass newly formed per unit of time. The present study confirms a previous investigation in which a higher LI was detected in association with hyperdiploidy. It shows that ts is simultaneously prolonged, while the DNA synthesis rate remains unchanged. This proves that in hyperdiploid cases the longer ts is caused by a larger amount of DNA to be synthesized. The FBR is the same for eu- and hyperdiploid, as well as for CALL and T-ALL cases, and there is no correlation between the FBR and the white blood cell count. So far, ALL is the only type of leukemia in which a prolongation of ts has been demonstrated in comparison to normal human lymphatic cells. This prolongation is not caused primarily by differences in ploidy. The type of growth is accumulative, since the relative rate of cell production is lower than normal. As a finding of practical importance, the labeling index is shown to correlate quite closely with the FBR. In this cell system the LI can thus be used as a parameter reflecting the rate of relative cell production.
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In two untreated patients with progressive CLL, quantitative 14C autoradiography of lymph nodes and, subsequently, continuous infusion of [3H] thymidine over eight and nine days, respectively, were performed in order to analyse the lymph node cell kinetics. Simultaneously, the turnover of labelled lymphocytes in the peripheral blood was evaluated. From another CLL patient a regional lymph node was removed 6 h after an intralymphatic flash injection of [3H] thymidine and sectioned for autoradiographic study of the distribution of labelled cells within the lymph node tissue. While the durations of DNA synthesis were found to be normal, the labelling indices were reduced. The relative cell production rate was far lower than normal. Very small growth fractions were calculated, amounting to less than 1% in one patient, and to 2.4% in the other. The distribution of labelled cells in the lymph nodes was focal, which supports the finding of low growth fractions. According to the present data, CLL is a disorder in which a very small number of cells cycle at a roughly normal rate. A kinetic definition of accumulative and proliferative tumour growth is introduced. Tumour growth is termed accumulative if growth appears to result from a decreased relative cell loss rate rather than an increased relative cell production rate. According to this definition, the kinetics in CLL may be classified as accumulative. In absolute terms, however, the number of lymphoid cells produced per unit of time was found to be far higher in CLL than in the healthy state.
A very sensitive measuring device for immunoflourescence and a new evaluation method were applied to detect the common acute lymphoblastic leukaemia antigen (cALLA) on individual cells from normal peripheral blood. Using a monoclonal and a polyclonal antiserum a small % (about 10%) of cells was shown to carry this antigen. In double-labelling experiments these cALLA positive cells were shown not to carry surface immunoglobulin, and very little T-antigen if any. During a 13-d cultivation of normal mononuclear blood cells in diffusion chambers, the cALLA positive cells disappeared but could be detected again on day 13 at a frequency comparable to that before culture. Proliferation is discussed as the mechanism accounting for the reappearance of the cALLA positive cells, perhaps due to the influence of the T-helper cells generated during culture.
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Auer-rod positive acute myelocytic leukemia (AML) blasts from a 33-year-old patient were cultured in diffusion chambers (DC) in order to test their differentiation potential. The cells were labeled with anti-human granulocyte anti-serum known to be negative for eosinophils, and evaluated using the unlabeled peroxidase-antiperoxidase (PAP) method. Parallel to a decline in the number of leukemic blasts there was an increase of up to 86% in the number of granulocytic cells belonging to the eosinophilic series. Auer-rod bodies were found in the eosinophilic cells even after 20 days in culture. Staining with anti-granulocyte antiserum failed to demonstrate positive cells at any time during DC culture. Based on the negative reaction with the anti-granulocytic antibodies already at an early stage of development evidence is provided for the existence of a progenitor cell exclusively committed to the eosinophilic pathway.
In PHA cultures of peripheral lymphocytes from three healthy donors the extent and time sequence of cALL and TdT positivity was followed over a period of seven days. In all cases significant percentages of cALL+ and TdT+ cells were observed. However, the period of positivity for both these markers tended to be short. In contrast to previous results with the diffusion chamber system which yielded a comparatively uniform pattern of positivity, PHA cultures of the present cases revealed a more heterogeneous pattern concerning the extent as well as the time sequence of positivity. These experiments provide a broader basis for the notion that those markers are expressed during blastogenesis of normal lymphocytes which are generally regarded as indicative of early lymphatic differentiation and of the stage of developmental arrest of acute lymphatic leukemias.
Peripheral blast cells from patients with acute lymphoblastic leukaemia were cultured in the diffusion chamber system. On different harvesting days the cALL antigen, surface immunoglobulin and T-cell antigen were investigated by direct immunofluorescence. Each cell type investigated showed a different response throughout culture, the commonest change observed being development into the B-cell axis. Our data demonstrate that the differentiation stop of a leukaemic cell can be overcome by using the diffusion chamber system. The data therefore give some insight into the stage of developmental arrest in acute lymphoblastic leukaemia.
Normal human mononuclear blood cells were cultured for 13 d in diffusion chambers and the cell harvest on days 3, 6, 9 and 13 was characterized according to morphology, growth kinetics and surface antigen expression. The greatest part of the cell harvest consisted on all days of lymphoid cells. It could be shown that most of the cells carried the T-cell marker, the main growing population thus being T-cells. The mean anti-T-binding capacity per cell increased during the initial lag phase and reached its peak when the cell count was lowest. It dropped again during the following exponential growth phase to preculture values. These changes indicate an initial increase in surface antigen during the transition of cells from resting to a more activated state before the onset of DNA-synthesis, and a subsequent decrease which may indicate functional maturation.
Blast cells derived from blood and marrow samples of a patient with acute lymphoblastic leukemia (ALL), as well as from the Reh line originally established from an ALL patient, were cultured in diffusion chambers implanted i.p. into preirradiated CBA mice. At different intervals over a period of up to 20 days, surface immunoglobulins, ALL antigen, and T-cell antigen were investigated by using direct immunofluorescence. Rosette formation was tested with sheep and mouse erythrocytes. On day 0, the cells expressed only ALL antigen at the surface, and no rosette formation was observed. During culture the patient's lymphoblasts, which originally had cytoplasmic IgM in addition to ALL antigen, expressed surface immunoglobulins as well as mouse erythrocyte receptors. The Reh line cells were ambivalent in two experiments developing T-cell antigens and sheep erythrocyte receptors as well as mouse erythrocyte receptors. Our data suggest that the differentiation arrest in leukemic lymphoblasts can be overcome, thus entailing a surface pattern similar to mature T- or B-lymphocytes.
Peripheral mononuclear blood cells of 2 healthy individuals were cultured over a 13 d period in diffusion chambers. A high percentage of cALL antigen positive cells and later on TdT containing cells appeared during culture. The cALL+ cells could be clearly distinguished into 2 groups: a population with weak and diffuse fluorescence and a small number of ring-like brightly dyed cells. The first group develops into TdT+ cells and therefore resembles immature T-cells. The interpretation of the ring-like stained cells is still preliminary, but it cannot be excluded, that these cells represent a cell population with more than lymphatic differentiation capacity.
Evidence for short sequences of interlimb coordination was found in 20-day-old rat fetuses. Frame-by-frame analysis of videotape records showed phase relationships indicating a pattern of alternation in sequences involving forelimb-forelimb and hindlimb-hindlimb coordination. Forelimb-hindlimb coordination was not observed.
The growth of mononuclear human peripheral blood cells from five patients with aplastic anemia (AA) was tested in diffusion chambers over a period of 13 days. Considerable differences were seen in the total cell number compared with controls. The total cell number of three patients with AA was markedly lower than in the control group (eight controls). The differentiation of the cells showed considerable differences in the growth patterns of the lymphocytes and in granulopoiesis; in three of five patients with AA no granulopoiesis was observed.
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