Large granular lymphocytes and neutropenia in a patient with ankylosing spondylitis.
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Agranulocytosis↗
Biomedical subjects
F Roubinet
Publications and source records attributed to F Roubinet.
Effects of an anti HLA-DR immunotoxin on leukaemia cells and hematopoietic progenitors.
An anti HLA-class II immunotoxin has been prepared by coupling to ricin A-chain (RTA) and anti-DR-DP monoclonal antibody (2G5-MoAb). Protein synthesis inhibition assays showed that 2G5-RTA immunotoxin is: highly cytotoxic to B-cell lymphoid neoplastic cells, and variable so to ALL cells, while AML cell lines display a generally poor susceptibility. Toxicity of 2G5-RTA on normal hematopoietic cells (HPC) was found to be dose-dependent, and to increase significantly with the addition of NH4Cl, used as an activating agent. After 4 h of incubation with 2G5-RTA (10(-8) M), without NH4Cl, percentages of CFU-GM and CFU-GEMM (colony forming units-granulo-monocytes and -multipotent, respectively) progenitor cell recovery were in the order of 50% and 30% respectively. In the same treatment conditions, 2G5-RTA induced a 6 log kill on RAJI cells--measured by clonogenic assay. Finally, this study shows that anti-DR immunotoxins may represent an original, efficient, and relatively safe approach for bone marrow purging of DR positive malignant B-cell populations; while their clinical potential pertaining to ALL and AML remains uncertain.
Animals↗
Sensitivity of fresh leukemic cells to T101 ricin A-chain immunotoxin: a comparative study between Fab fragment and whole Ig conjugates.
We compared the cell killing potency of a whole Ig ricin A-chain immunotoxin (T101 IgG-RTA) against its Fab fragment counterpart (T101 Fab-RTA) on both CEM cells and fresh malignant lymphoid cells. A dye exclusion assay (DEA), was used to evaluate the kinetics of leukaemia cell viability mediated in vitro by each immunotoxin (IT). This study found that in the absence of ammonium chloride (NH4Cl), used as an enhancer agent, T101 Fab-RTA was significantly more toxic to both CEM and fresh leukaemia cells than T101 IgG-RTA. In the presence of NH4Cl (10(-2) M), while no differences could be found between the two IT on CEM cells, T101 Fab-RTA was clearly superior to T101 IgG-RTA on fresh leukaemia cells. These results suggest that T101 Fab-RTA may offer an excellent alternative to T101 IgG-RTA for IT treatment of CD5 positive leukaemia patients.
Ammonium Chloride↗
[Immunopharmacologic study in mice of 2 beta-1, 3, beta-1, 6 polysaccharides (scleroglucan and PSAT) on the activation of macrophages and T lymphocytes].
The immunopotentiating activity and mechanisms of PSAT and scleroglucan, two beta 1-3, beta 1-6 glucan, were investigated in mice: these polysaccharides increase the chemiluminescence of peritoneal phagocytes and the serum C3 level. Augmentation of DNA synthesis of spleen cells was induced in vivo by injecting PSAT or scleroglucan. An additional proliferative effect of these polysaccharides was observed when spleen cells were incubated with mitogens. Moreover, PSAT enhances the number of Thy1 lymphocytes and increases the ratio of lymphocytes L3T4/Lyt2 in mice infected with Toxoplasma gondii. No significant changes in immunoglobulin levels were found. These data indicate that PSAT and scleroglucan favorably affect the non-specific host defense and cellular immune response in mice.
Animals↗
Characterization of two factors enhancing choline acetyltransferase activity in cultures of purified rat motoneurons.
Motoneurons from E14 rat embryos have been retrogradely labeled with the carbocyanine derivative dil and purified 12-fold by centrifugation on a density gradient made of Nycodenz, as assessed by the increase in CAT activity per cell and in the percentage of dil-labeled cells. A 20- to 36-fold purification was achieved by the microdissection of the labeled lumbar motor columns followed by density-gradient centrifugation. Motoneurons were then purified to near homogeneity by fluorescence-activated cell sorting. In certain experiments, motoneurons were purified by a novel cell-sorting procedure that only uses light-scatter parameters and does not necessitate retrograde labeling. In cultures of motoneurons enriched by centrifugation, muscle-conditioned media (CM) had only a marginal effect on the overall neuronal survival but increased up to 10-fold the number of labeled motoneurons surviving after 7 d in culture. CAT activity per culture was quantitatively stimulated to the same extent, suggesting that the increase in CAT activity caused by CM mostly reflected better survival of motoneurons. In cultures of motoneurons purified by cell sorting, CM increased both survival and CAT expression per motoneuron. We have partially purified 2 factors from CM that stimulate CAT activity per motoneuron 2- to 3-fold without affecting their survival. One of these factors is probably identical to the factor involved in the cholinergic/noradrenergic choice of sympathetic neurons (Fukada, 1985).
Animals↗
Patulin immunotoxicology: effect on phagocyte activation and the cellular and humoral immune system of mice and rabbits.
Patulin is a mycotoxin frequently found in rotten apples or molded corn. We have investigated the effect of sublethal doses of patulin on the immune system in mice and rabbits. A significant suppression of the chemiluminescence response of peritoneal leucocytes was observed in both species. Mouse spleen lymphocytes showed a decrease in absolute number, most pronounced for the B-cell population whereas the Ts population showed a relative increase after patulin treatment. The mitogenic response to PHA, Con A and, in particular, PWM was also depressed by patulin. This was paralleled by decreasing serum immunoglobulin levels in the mice and rabbits. The immunosuppressive effect of patulin is reversible and is probably due to interaction with cellular free SH groups since the action of patulin can be circumvented, at least partially, by the prior administration of cystein. Under natural circumstances, patulin may constitute a health risk for animals.
Animals↗
The transsynovial lymphocytic ratio. Characterization of blood and synovial fluid lymphocytes from patients with arthritic diseases.
Monoclonal antibodies and flow cytometry techniques were used to analyze and compare the distribution of lymphocyte subpopulations of peripheral blood and synovial fluid (SF) from 70 patients, 43 with rheumatoid arthritis (RA), 10 with ankylosing spondylitis (AS) or reactive synovitis, 10 with psoriatic arthritis and 7 with other inflammatory arthritic diseases. Patients with RA had significantly reduced number of CD8+ T cells and greater CD4/CD8 ratios in peripheral blood, a greater number of CD4+ T cells and lower CD4/CD8 ratio in SF. No significant difference was found between the groups with AS, reactive synovitis and psoriatic arthritis. The simultaneous analysis of peripheral blood and SF lymphocyte subpopulations allowed us to establish a transsynovial lymphocytic ratio which reflects CD4/CD8 variations on both peripheral blood and SF, 2 easily accessible compartments for physicians. This new ratio may distinguish RA from other inflammatory arthritic diseases.
Arthritis↗
Influence of 12-O-tetradecanoylphorbol-13-acetate on proliferation and maturation of human breast carcinoma cells (MCF-7): relationship to cell cycle events.
Exposure of MCF-7 human mammary carcinoma cells to 12-O-tetradecanoylphorbol-13-acetate (TPA) results in changes in cell morphology and arrest of cell growth. The inhibition of cell proliferation and the increase in cell volume are concentration dependent; these effects are reversible upon removal of the tumor promoting agent. Electron microscopic studies reveal that TPA increases endoplasmic reticulum and induces the appearance of secretory granules. MCF-7 cells treated by TPA therefore present morphological characteristics of secretory cells. These effects of TPA on MCF-7 cells are accompanied by specific disruption of cell cycle events, a block of cells in G1 at the expense of S base, and a delayed passage through G2. Studies in which a cell cycle lock in G1 is produced by tamoxifen show that exposure of such cells to PA produces cell morphological changes and an inability to progress through the cell cycle when estradiol is added.
Breast Neoplasms↗
[Lymphocyte subpopulations in blood and articular fluid in rheumatoid polyarthritis].
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Adolescent↗
[Description and performance of a flow cytometry apparatus: the EPICS].
This is a report on our experience with the EPICS C (Coultronics) cytometric flux apparatus, a screening cell analyzer, employing a laser ray (2 or 5 watts); we obtained good results to analyze immunologically-tagged mononuclear blood cells with or without prior separation: for rhythm, repeatability, and contamination. The EPICS C machine proved to be effective to study the cell cycle using lymphoblastic cells, epithelial cells and cells from a breast cancer. Several screening trials were carried out with fluorescent ball bearings of various sizes; the quality of screening (purity and yield) appear optimal at a speed ranging from 500 to 1,000 bearings per second, using three parameters: the logarithm of green fluorescence, the integral function of green fluorescence, the diffraction of light to small angles. Thus, if results obtained for this analysis are entirely satisfactory, the screening function remains limited because it is slow.
Cell Cycle↗
t(14;14)(q11;q32) in biphenotypic blastic phase of chronic myeloid leukemia.
A blastic crisis of chronic myeloid leukemia without a detectable chronic phase is reported. At diagnosis, blast cells present t(9;22)(q34;q11),t(14;14)(q11;q32) translocations and early B cell phenotype (DR +, TdT +, B4 +, BA1 +, J5 +). At relapse, the malignant clone evolves to a biphenotypic expression, the initial markers remain unchanged, and two myeloid antigens (My 7, My 9) appear. The wide overlap in percentages of blast cells displaying lymphoid and myeloid markers shows that a single clone bears antigens of both lineages. Simultaneous occurrence of a t(14;14)(q11;q32) translocation, usually found in T cell malignancies, and of a B cell phenotype raises the question of the relationship between chromosomal changes and surface marker expression. The malignant cell is assumed to be a progenitor cell, already committed to lymphoid lineage and retaining the potential to switch to myeloid lineage.
Aged↗
Local immunotherapy of recurrent glioblastoma multiforme by intracerebral perfusion of interleukin-2 and LAK cells.
A non randomized pilot study has been undertaken to evaluate the feasibility of local immunotherapy (IT) of recurrent glioblastoma multiforme (GM) by continuous intracerebral perfusion of recombinant interleukin-2 (rIL-2, Eurocetus) with and without lymphokine activated killer (LAK) cells. At time of surgical removal of the tumor, a catheter was implanted in the cavity left by tumor debulking allowing continuous perfusion of rIL-2. Five patients received 18 x 10(6) IU/day or rIL-2 for five days. At days 1, 3, and 5 after surgery, rIL-2 perfusion was briefly interrupted for the injection of LAK cells. Eight other patients received rIL-2 alone, either 24 x 10(6) IU/day (five patients) or 54 x 10(6) IU/day (three patients). Capillary leak syndrome, which is the main side effect of systemic infusion of rIL-2, was never observed, but local immunotherapy induced fever, confusion, and cerebral edema in all patients. Despite local IT, tumor progression was diagnosed by CT scan 4 to 12 weeks after the treatment.
Adult↗