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Biomedical subjects

V Praloran

Publications and source records attributed to V Praloran.

At least 19 recordsLinked to original sources
PubMed1995

PAF and haematopoiesis: III. Presence and metabolism of platelet-activating factor in human bone marrow.

Platelet-activating factor (PAF) is a phospholipid compound with major immunoregulatory activities. The present study shows that human bone marrow contains 576 +/- 39 pg PAF/ml (n = 35). Bone marrow-derived PAF exhibits the same biophysical and biological properties that synthetic PAF. PAF concentrations in bone marrow are correlated with the granulocyte (r = 0.4, P = 0.02) but not with the lymphocyte (r = 0.24, P = 0.17) and the monocyte (r = 0.12, P = 0.48) counts. In bone marrow PAF is inactivated by a plasma PAF acetylhydrolase activity (48.0 +/- 2.3 nmol/min per ml, n = 34). Experiments with [3H]PAF indicate that human bone marrow cells actively metabolize this potent molecule by the deacetylation-transacylation pathway. Results of this investigation indicate the permanent presence of significant amounts of PAF in bone marrow suggesting its putative involvement in the processes of bone marrow cell proliferation and maturation.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1995

PAF and haematopoiesis. IV. Modifications of spleen and thymus PAF contents after a single dose of the chemotherapeutic drug 5-fluorouracil in mice.

The spleen and thymus of mice were examined for the presence of PAF after injection of 5-fluorouracil (5-FU) (200 mg/kg). A significant increase of the spleen (P = 0.005) and thymus (P < 0.05) PAF concentrations was noted 48 h after 5-FU infusion. PAF levels in thymus are similar to those of controls from days 4 to 14. By contrast, spleen PAF significantly decreased (0.005 < P < 0.03) from days 7 to 14. Conversely, the 5-FU administration did not modify the spleen and plasma acetylhydrolase activity, suggesting that the variations of PAF levels in thymus and spleen were mainly due to differences of local PAF production. Thus, the chemotherapeutic drug 5-FU modulates in vivo PAF production in haematopoietic organs of mice. Considering the effects of PAF in the processes of B- and T-cell proliferation and functions, these results could be of importance for the role of PAF during human cancer therapy and haematopoiesis in vivo.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1995

Collagen matrix: an attractive alternative to agar and methylcellulose for the culture of hematopoietic progenitors in autologous transplantation products.

Autografts using untreated or in vitro manipulated bone marrow and peripheral blood stem cells represent promising approaches to the treatment of malignant diseases. In this work, the collagen gel culture technique was compared with agar and methylcellulose for its capacity to permit the growth of human granulomonocytic (day 14 CFU-GM; collagen vs agar or MTC) or erythroblastic (day 7 CFU-E and day 14 BFU-E; collagen versus methylcellulose) colonies in autologous transplantation products. Our results show that the collagen culture system always gave as many or more colonies than the other techniques. It also allowed harvesting of gels onto glass slides and subsequent May-Grünwald-Giemsa, cytochemical or immunocytochemical staining. We suggest that the collagen assay represents an interesting alternative to the widely used agar or methylcellulose systems for the culture of hematopoietic progenitors because of the equal or higher number of colonies detected, the easy phenotypical identification of colonies in stained gels, and the ability to store high-quality documentation. This technique is particularly attractive for use in the quality control of autologous bone marrow transplantation procedures.

Agar↗
PubMed1995

AcSDKP serum concentrations vary during chemotherapy in patients with acute myeloid leukaemia.

AcSDKP is a physiological negative regulator of cell proliferation in mammals. In Ara-C-treated mice its plasmatic concentrations decrease while the CFU-S start cycling. Infusion of AcSDKP protects these animals from death by blocking the proliferation of primitive haemopoietic cells. We measured AcSDKP serum concentrations in 20 AML patients during the course of high-dose cytoreductive treatment. We observed an early and sharp increase of AcSDKP during the induction treatment in 12 patients, reaching a peak during the initial 3 d of treatment in nine of them. These results are contrary to those observed in mice treated with high doses of Ara-C. They encourage further clinical investigation, and suggest that treatments with synthetic AcSDKP (Seraspenide) will perhaps have to be adjusted to the type of disease and the schedule of chemotherapy in order to optimize its myeloprotective effect.

Acute Disease↗
PubMed1992

Enhanced hematopoietic growth factor production in an experimental myeloproliferative syndrome.

The murine myeloproliferative syndrome induced by the myeloproliferative sarcoma virus (MPSV) has numerous similarities to human primary myelofibrosis. We have shown that medium conditioned by spleen cells of MPSV-infected mice has the capacity to support the growth of primitive blast cell colonies. The detection of this activity associated with MPSV infection stimulated us to characterize the hematopoietins responsible for this activity. Northern blot analysis showed a large increase, or induction, of interleukin-6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage-CSF (CSF-1), and granulocyte-CSF (G-CSF) transcripts in the hematopoietic organs of MPSV-infected mice; however, no IL-3 transcript could be detected in either MPSV-infected or normal mice. Significant levels of IL-1 alpha, IL-6, G-CSF, and CSF-1 bioactivities were found in the serum of MPSV-infected mice, but not in controls. Additionally, analysis of medium conditioned by spleen cells of MPSV-infected mice showed the presence of tumor necrosis factor alpha bioactivity. The increased production of cytokines that are able to stimulate pluripotent hematopoietic stem cells corroborates the hypothesis of a possible involvement of hematopoietic growth factors in the development of some myeloproliferative disorders.

Animals↗
PubMed1992

Primary Epstein-Barr virus infection with clonal T-cell lymphoproliferation.

A case of fatal Epstein-Barr virus infection in a previously healthy girl who was first found to have severe infectious mononucleosis with spontaneous recovery is reported. Because an abnormal immune response to the virus persisted, the disease relapsed, manifesting in cutaneous and pulmonary lesions associated with hemophagocytic syndrome responsible for death. Pathologic findings were characterized by polymorphous atypical lymphoid infiltrate, prominent necrosis, and histiocytic hyperplasia. Lymphoid cells displayed CD8 phenotype and clonal T-cell receptor gene rearrangement. Viral genome was detected in lesions by Southern blot and located in nuclei of lymphoid cells by in situ hybridization. Pathologic findings suggested fatal infectious mononucleosis; however, phenotype and genotype favored a malignant diagnosis. Clonality was demonstrated to have arisen during primary infection. Virologic examination indicated that Epstein-Barr virus was a causative agent. Such a process belongs to the recently recognized spectrum of Epstein-Barr virus-related T-cell lymphoproliferative disorders that might overlap fatal infectious mononucleosis in patients who are especially vulnerable to the virus.

Adolescent↗
PubMed1992

Immunohistochemical detection of cells positive for colony-stimulating factor 1 in lymph nodes from reactive lymphadenitis, and Hodgkin's disease.

Colony-stimulating factor 1 (CSF-1) is a cytokine involved in hematopoiesis and perhaps more importantly in the early stages of immunological defense mechanisms. Although numerous studies of in vitro CSF-1-producing cells have been published, in vivo data is totally lacking. According, we performed immunohistochemical detection of CSF-1-positive cells on frozen sections of reactive lymphadenitis (three cases) and Hodgkin's disease (13 cases) lymph node biopsies, using as antibody a highly specific polyclonal rabbit antiserum prepared in our laboratory. Endothelial cells from high endothelial venules and most fibroblasts were positive in all cases (reactive lymphadenitis and Hodgkin's samples), and most lymphocytes in interfollicular T cell areas showed faint granular positivity in reactive lymphadenitis lymph nodes. Hodgkin and Reed-Sternberg cells were positive in all cases tested, although staining intensity was highly variable and the percentage of positive cells differed from case to case. These data from in vivo biopsies confirm previous results for in vitro CSF-1 production by endothelial cells, fibroblasts, T lymphocytes, and Hodgkin cell lines. They are consistent with the role of this cytokine in immune response and raise the question of its significance in Hodgkin's disease.

Hodgkin Disease↗
PubMed1992

Accumulation of T-cell clones producing high levels of both granulocyte-macrophage and macrophage colony-stimulating factors (CSF-1) in lymph nodes involved by Hodgkin's disease.

We have previously shown that total T cells derived from lymph nodes (LN) involved by Hodgkin's disease (HD) secrete higher levels of colony-stimulating activity than total T cells present within benign hyperplastic (BH) LN and B-non-Hodgkin's lymphoma (B-NHL) LN, suggesting that T cells with particular properties accumulate in HD LN. To further characterize this T-cell population, we have quantified production of both granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) production in a total of 98 T-cell clones (TCC) derived from CD25+ activated T cells present in HD LN; TCC derived from CD25+ T cells obtained from B-NHL LN(101 TCC), BH LN(95 TCC), and peripheral blood (PBL; 38 TCC) of healthy donors were used as controls. HD LN were characterized by the presence of an elevated number (44%) of TCC producing particularly high titers of both GM-CSF and M-CSF, whereas only a minority of such TCC was found in control groups (10% in B-NHL, 16% in BH, 8% in PBL). These observations support the hypothesis of a selection of T-cell families with particular properties occurring in contact with Reed-Sternberg (RS) cells. According to the biological properties of GM-CSF and M-CSF, it seems reasonable to suggest the involvement of this particular subset of T cells in the granulomatous process, the peripheral blood polynucleosis, and in the paracrine growth of RS cells.

Clone Cells↗
PubMed1991

Macrophage colony-stimulating factor (CSF-1) gene expression in human T-lymphocyte clones.

Macrophage colony stimulating factor (CSF-1) is one of several cytokines that control the differentiation, survival, and proliferation of monocytes and macrophages. A set of 11 human T-cell clones, chosen for their phenotypic diversity, were tested for their ability to express CSF-1 mRNA. After 5 hours of stimulation with phorbol myristate acetate (PMA) + calcium ionophore (Cal), all T-cell clones expressed a major 4-kb transcript, a less abundant 2-kb transcript, and several other minor species. This pattern of expression is typical for CSF-1 mRNAs. Furthermore, of the two alloreactive T-cell clones analyzed, only one showed a definitive message for CSF-1 on specific antigenic stimulation, but with delayed kinetics and less efficiency. Both conditions of stimulation induced the release of CSF-1 protein by T cells in the culture medium. Together, these findings demonstrate for the first time that normal T cells are able to produce CSF-1, previous reports being limited to two cases of tumoral cells of the T-cell lineage.

Antigens↗
PubMed1991

Purification and biological properties of vasculotropin, a new angiogenic cytokine.

Angiogenesis is a key step in organ development and remodeling during embryogenesis or tissue regeneration. Some pathological events such as tumor growth or diabetic retinopathy also lead to angiogenesis formation. Several molecules have already been identified as promoting angiogenesis in vivo. Whether their bioactivity is mediated by other angiogenic growth factors or not is still unclear. We identified and purified recently a new angiogenic growth factor. Its unique specificity for vascular endothelial cells led us to provisionally name it vasculotropin (VAS). We describe the biochemical properties of VAS and its biological functions. Structural data showed that VAS is related to the SIS family. In vivo VAS was recognized as an inducer of angiogenesis and vascular permeability. In vitro, despite a moderate action on proliferation, VAS strongly stimulates the cell migration. The screening of the presence of cellular receptors and VAS production showed that the cells which bind VAS do not synthesize it, whereas the cells which synthesize VAS do not bind it. Thus, VAS seems to act through a paracrine pathway. We also present data suggesting that VAS has a lymphokine activity.

Amino Acid Sequence↗
PubMed1991

Structure, biosynthesis and biological roles of monocyte-macrophage colony stimulating factor (CSF-1 or M-CSF).

CSF-1 or M-CSF is a homodimeric glycosylated protein purified to homogeneity through its hematopoietic growth factor properties. It has recently been cloned and sequenced as a unique gene encoding several m-RNAs and peptidic species. Its receptor has been identified as the c-fms protooncogene product expressed at the surface of all CSF-1 responsive cells as a transmembrane tyrosine kinase responsible for CSF-1 induced signal transduction. CSF-1 is permanently present in serum and several biological fluids at stable concentrations and can thus be considered as a hormone. In vivo concentrations are mainly regulated by binding, internalization and degradation of the CSF-1 molecule by hepatic and splenic macrophage receptors. Very little is known about the organs and cell types responsible for in vivo CSF-1 synthesis. In vitro, CSF-1 regulates the survival, proliferation and differentiation of the monocyte-macrophage lineage from progenitors to mature cells and activates several important functions of mature tissular macrophages. Recent results obtained with injections of recombinant CSF-1 show that interesting activities, e.g., as ADCC, NK or antiinfectious effects, that had been initially observed in vitro can also be induced in vivo. All these in vitro and in vivo data and the recent availability of large amounts of pure recombinant human CSF-1 point to the diagnostic value of CSF-1 concentration measurements in biological fluids and suggest a therapeutic role for CSF-1 infusion in cancer and infection therapy.

Animals↗
PubMed1991

[Mitogenic activity of vasculotropin for peripheral human lymphocytes].

Vasculotropin is a growth factor with a unique specificity for vascular derived endothelial cells. We report that normal human peripheral lymphocytes represent another target for vasculotropin. The mitogenic activity of the medium conditioned by these cells cultured in the presence of Concanavalin A is potentiated by vasculotropin. This effect is exerted more likely through interactions with the soluble mediators rather than through the VAS receptors since VAS binds equally to Concanavalin A stimulated and to unstimulated lymphocytes.

Concanavalin A↗