Cipropride in preventing nausea and vomiting induced by severely emetic cytostatic agents.
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Biomedical subjects
Publications and source records attributed to C Rosenfeld.
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We measured the fluorescence polarization of 1-6 diphenyl hexatriene in mononucleated cells from the peripheral blood of 49 acute lymphoid leukemic patients in complete hematological remission with an Elscint MV-1 microviscosimeter. The measurements of fluorescence polarization were made at various times after the remission was achieved. Our results represent two years of this prospective study. We found that lymphoid leukemic patients in remission could be separated into two groups according to the lowest value of fluorescence polarization of their blood cells. 1) The first group of 26 patients showed values superior to 3.44 poises, in all samples, corresponding to the lowest value of normal controls. 2) The second group showed at least one value of blood fluorescence polarization lower than 3.44 poises. This second group had a significantly lower median duration of remission and survival compared to the first. We have subdivided these two groups according to other established prognostic parameters such as cytological subtype and initial volume of the disease: we found that cellular fluorescence polarization could give additional prognostic information. These data suggest that fluorescence polarization measurements have a prognostic value to follow acute lymphoid leukemia patients in complete remission: when a low value is found there is a significant risk of relapse.
Of 25 patients with acute lymphoid leukemia (ALL) in remission who were submitted to immunotherapy with BCG plus irradiated REH cells, 17 had positive sera in microcytotoxicity against REH cells after immunization. The follow-up of 28 months indicates that the microcytotoxicity varies in the same patient and may become negative and positive again. The results obtained after convenient absorption of one positive serum strongly suggest that REH cells in leukemic patients can raise antibodies directed against an antigenic structure closely related to the cALL antigen. Moreover, REH cells demonstrate in vitro suppressive activity, which could be a common property of some subcategories of human ALL.
We have demonstrated that splenic lymphocytes from normal syngeneic animals can stimulate tumor growth. This effect is T-cell dependent. Preincubation of these lymphocytes with thymosin not only blocks facilitated tumor growth but can induce a significant reduction of local tumor growth and number of pulmonary metastases. Furthermore, thymosin can also block the expression of suppressor activity of lymphocytes either stimulated by Con A or originating from various advanced solid tumor bearing patients. These results therefore suggest that thymosin is able to modulate, directly or indirectly, functional expression of suppressor cells.
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A semi-automatic method for recognition of chromosomal changes is presented: from a coded description of an abnormal chromosome (formulated with the aid of an R-banding technique), a computer program makes simulations to reconstitute this chromosomal image from a group of normal chromosomes. Nine types of aberrations (see text) can thus be recognized and the aggregate structure of a group of abnormal chromosomes occurring in a human karyotype can also be rediscovered.
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The treatment of human lymphoblastoid cell cultures with the phorbol diester, 12-O-tetradecanoyl-phorbol-13-acetate, a tumour promoter, caused at nM concentration surface structural changes associated with altered adhesion properties. The effect was observed in several cell lines from normal or leukaemic origin. In addition, the tumour promoter induced an early and transitory growth inhibition which was observed in all tested B-characteristic cells. The phorbol diester, 4-O-methyl-phorbol-12,13-didecanoate, which is devoid of tumour-promoting activity, was much less effective in altering cell adhesion properties and cell growth than the active derivative. These observations suggest that lymphoblastoid cells may be a useful model for studying the molecular alterations at the membrane level resulting from the action of tumour-promoting phorbol diesters.
The effect of thymosin on suppressor-cell function was evaluated in vivo in a murine tumor system and in vitro on human lymphocytes. In mice, the Lewis tumor system was used. We showed that splenocytes from tumor-bearing animals were able to enhance tumor growth in a syngeneic system. This enhancement was similar when thymocytes from tumor-bearing animals were used and disappeared after anti-Thy 1-2 antiserum treatment, suggesting a T-dependence. Treatment of the tumor-growth-enhancing lymphocytes with corticosteroids or irradiation caused this effect to disappear completely suggesting that the tumor-growth-enhancing T-lymphocytes were suppressor T-cells. Furthermore thymosin (fraction 5)-treated, tumor-growth-enhancing T-lymphocytes were not able to enhance tumor growth and even significantly decreased it. In the human system we showed that Con A-stimulated lymphocytes were able to suppress the response of normal lymphocytes to PHA, PWM, and Con A, and in MLC. This effect was significantly blocked in presence of thymosin fraction 5.
Fluorescence polarization (FP) of diphenylhexatriene (DPH) has been currently interpreted as cell membrane fluidity. We studied here FP of DPH labelled platelets under activation of membrane enzymes and concluded that FP of DPH could rather reveal interactions with hydrophobic pockets of membrane proteins.
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We describe an improved method for the determination of organic phosphorus from phospholipids. It is the combination of a very fast mineralization step followed by the estimation of liberated phosphate by means of malachite green. This method is accurate, simple, and sensitive.
Steady-state fluorescence polarization studies with the fluorescent lipid probe 1,6-diphenyl 1,3,5-hexatriene were done to determine the degree of microviscosity of cellular membrane lipids and serum lipoproteins in human normal donors and leukemic patients. The results show a marked decrease in microviscosity of cellular membrane lipids in both intact lymphocytes and isolated cellular plasma membranes obtained from leukemic patients in clinical relapse as compared to intact lymphocytes and isolated cellular plasma membranes obtained from normal donors and leukemic patients in complete clinical remission. Concomitant to these dynamic changes in cellular membrane lipids, the degree of microviscosity of lipids in the blood serum of leukemic patients in clinical relapse is markedly reduced as compared to serum obtained from normal donors and leukemic patients in complete clinical remission. Moreover, an in vitro incubation of leukemic lymphocytes with normal low density lipoproteins results in an increased microviscosity of cellular membrane lipids. In addition to the interrelation between cellular membrane lipids and serum lipoproteins, plasma membrane vesicles with a high degree of lipid microviscosity were isolated from the blood serum and pleural effusion of leukemic patients in clinical relapse. Such membrane vesicles could not be detected in normal serum. Therefore, we suggest that the two major mechanisms associated with the decreased microviscosity of membrane lipids in human leukemic cells are an abnormal exchange in lipids between the leukemic cell surface membrane and leukemic serum lipoproteins and an exfoliation of plasma membrane vesicles with a high degree of microviscosity from the cell surface of leukemic cells.
A new lymphoid cell line, Reh 6, has been established from the peripheral blood of a patient with acute lymphocytic leukemia. Reh 6 cells were assayed for the presence of Epstein-Barr virus (EBV) DNA by nucleic acid hybridization and for Epstein-Barr nuclear antigen (EBNA) by the immunofluorescence test. Reassociation kinetics between in vitro [3H]-labeled EBV DNA and Reh 6 cell DNA indicated the absence of detectable amounts of EBV DNA in Reh 6 cell DNA. In addition, attempts to detect EBNA by the immunofluorescence test in Reh 6 cells were unsuccessful. Thus, this new lymphoid cell line apparently lacks the EBV genome.
A comparative chromosomal analysis was made of 10 human lymphoblastoid cell lines, four of which originated from normal donor lymphocytes and six of which were from leukemic peripheral blood. For comparison of lymphoblastoid cells with respect to their normal or leukemic origin, cytogenetic studies have been carried out regularly since the beginning of the culture during more than 3 years. Samples were drawn during the three phases previously described for the establishment of these lines. The chromosome distribution remained diploid for at least 2 years in normal cell lines, and the cells were euploid. In contrast, an important variability of the chromosome set was demonstrated during the same period in leukemic cell lines. Moreover, in these lines, it was always possible to observe a nonsystemic pseudodiploidy. After 2 years, a clonal evolution was described in both types of cell lines that carried at least one marker. With a controlled-heating denaturation technique, it was possible to identify the markers as specific to each cell line. The cells with marker chromosomes appeared to have a selective advantage of growth.
Cell surface modifications after vibrio cholerae neuraminidase treatment were investigated using three different tritiated lectins: Concanavalin A, Ricinus sanguineus agglutinin (R.S.A.) and Robinia pseudoacacia lectin. Lectin binding measurements were performed on untreated and enzyme treated cells. The cells used were from chronic and acute leukemic donors. After neuraminidase treatment, a significant increase in the number of receptor sites, from 1 to 3 times, was found in all cases tested and for all three lectins utilized with only one exception. The affinity constant was generally decreased after neuraminidase treatment. The increase in number lectin binding sites, indicating extensive modification of the cell surface, is completely consistant with the known importance of sialic acid in determining immunogenicity.
Amino acid analysis of the culture medium was carried out in a human leukemic lymphoblastoid cell line (REH) established from the lymphoblasts of a patient with acute lymphoid leukemia. The results are compared with those of a reference cell line (LHN13) established from normal human lymphocytes. The most striking difference between these two cell lines concerns proline. In LHN13 the concentration of this amino acid in the culture medium increases by 40 microgram/ml/10(6) cells during a 72-hr incubation. In REH there is a decrease under the same culture conditions. In both cell lines proline is derived from glutamic acid and from arginine, as found with the use of 14C-labeled precursors. Synthesis of proline in the REH line represents approximately 26% of the value measured in LHN13 when the precursor is glutamic acid and 15% when the precursor is arginine. The radioisotopic assay for delta1-pyrroline-5-carboxylate reductase showed that there is a deficiency of this enzyme in the REH cells. The defect in proline synthesis of REH was found at the establishment of this line and constitutes a metabolic marker that has persisted for more than 2 years.