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Biomedical subjects

S Castaigne

Publications and source records attributed to S Castaigne.

At least 91 records · Page 5Linked to original sources
PubMed1988

Action of interferon-alpha on hairy cell leukemia: expression of specific receptors and (2'-5')oligo (A) synthetase in tumor cells from sensitive and resistant patients.

IFN-alpha induces tumor regression with a high percentage of complete remissions in hairy cell leukemia. We have recently reported that hairy cells express specific IFN-alpha receptors which are down-regulated upon therapy. We show here that the activity of 2-5 A synthetase, an IFN-induced enzyme, is 2 to 7-fold stimulated in hairy cells from responsive patients within 12-24 h after the first IFN dose. This in-vivo enzyme induction paralleled the kinetics of receptor down-regulation. In one patient who was unresponsive to IFN-alpha treatment neither expression of IFN-alpha receptor nor change in 2-5 A synthetase were expressed and modulated as in sensitive patients. In-vitro treatment of hairy cells with recombinant interferons showed that IFN-beta 1 was able to induce this enzyme to the same extent than IFN-alpha 2, whereas IFN-gamma was inactive despite the presence of specific IFN-gamma receptors. Our results indicate that IFN-alpha can exert its therapeutic effects by acting directly on the hairy cells through interaction with surface membrane receptors. Induction of 2-5 A synthetase can be one of the steps involved in this action. However, both mechanisms, as well as receptor down-regulation are not sufficient to explain the responsiveness of hairy cell leukemia to IFN-alpha.

2',5'-Oligoadenylate Synthetase↗
PubMed1988

[Autografts of blood cells at various stages].

Thirty-nine patients with acute myeloblastic or lymphoblastic leukaemia had peripheral blood mononuclear cells collected by 3 continuous-flow leukapheresis as they entered first remission after induction chemotherapy. CFU-GM were assayed as a measure of the number of haemopoietic stem cells in each collection. Numbers of CFU-GM harvested varied among the patients (for example 0.27 to 155.10(4)/kg for ANLL patients). Nineteen patients underwent peripheral blood stem cells autografts after a conditioning regimen with high dose cyclophosphamide and TBI. The patients were transfused with a median of 2.2.10(4)/kg CFU-GM cells (0.28 to 100.10(4) CFU-GM/kg). Only 1 patient had a graft failure. The rate of haemopoietic recovery was studied for our patients and those reported in the literature. A strong correlation exists between the numbers of CFU-GM transfused and the rate of granulocytes and platelets recovery. Very rapid recovery are regularly obtained when the number of CFU-GM transfused is superior to 5.10(4)/kg.

Adult↗
PubMed1988

[Adult T-cell leukemia associated with HTLV1 and positive HIV2 serology in an African woman].

We report a case of acute adult T-cell leukemia associated with HTLV1 infection in a young African woman. The leukemic proliferation consisted of CD4-, CD25-positive lymphoid cells with typically convoluted nuclei and monoclonal integration of the HTLV1-proviral DNA. The clinical course was characterized by a rapid progression of the leukemia with development of hypercalcemia, resistance to chemotherapy, and the presence of multiple opportunistic infections. The additional finding of a seropositivity for HIV2 raises the problem of the respective contribution of the two retroviruses in this patient's disease.

Acquired Immunodeficiency Syndrome↗
PubMed1988

[Treatment of hematologic diseases with alpha interferon].

Since 1970, several trials conducted with natural alpha interferon have allowed the recognition of sensitive disorders to this new type of treatment. These studies are ongoing now with recombinant alpha interferons in hairy cell leukaemia, low grade lymphomas, myeloproliferative disorders and myeloma.

Humans↗
PubMed1987

Alpha-interferon in hairy cell leukaemia: direct effects on hairy cells or indirect cytotoxicity?

This report presents the results of a clinical trial on 53 patients with hairy cell leukaemia using low-dose alpha-interferon as therapy. Improvement of cytopenia and/or bone marrow hairy cell infiltration occurred in all but one patient. Often, blood and bone marrow improvements were dissociated and, after 7 or 13 months of therapy, complete remission was only observed in about 40% of patients. Recurrence of the disease was observed in some cases after cessation of therapy. A summary of the following results is presented: alpha-interferon receptor analysis, oncogene expression, study of the sensitivity of hairy cells to natural killer cells, and the effects of interferon on T-cell receptor gene rearrangement and on the function of T-cell clones. Results are also presented which show that myelofibrosis may be due to a release of platelet derived growth factor. The immunological findings and oncogene expression in 2 patients with a variant form of hairy cell leukaemia for which resistance to therapy was observed are also described. All the results show that interferon acts on hairy cells and are consistent with a direct effect by interferon in the treatment of hairy cell leukaemia.

Blood Platelets↗
PubMed1987

Platelet acquired defect in PDGF and beta thromboglobulin content in hairy cell leukaemia: improvement after interferon therapy.

To investigate the platelet contribution to the development of myelofibrosis in hairy cell leukaemia (HCL), we have studied two platelet alpha granule components in 15 patients with HCL before chemotherapy: mitogenic activity was measured by 3H thymidine incorporation in BALB/C 3T3 cells and beta thromboglobulin (beta TG) assayed by radioimmunoassay (RIA). Platelet mitogenic activity and beta TG content were significantly decreased in the patients as compared to the control subjects. The nine patients who were treated with recombinant human interferon (IFN alpha A) were restudied after 4 months of therapy. The levels of both mitogenic activity and beta TG platelet content were significantly increased after IFN alpha-treatment with a complete response in five of the nine treated patients, a partial response in two and no response in the two others. HCL seemed therefore to be responsible for an acquired platelet alpha granule defect. As in the grey platelet syndrome a relationship between this abnormal platelet granule storage and the development of myelofibrosis is suggested in HCL.

Blood Platelets↗
PubMed1987

Long-term human blood cultures: application to circulating progenitor cell autografting.

Peripheral blood cells collected by cytapheresis from patients with acute leukemia following induction therapy or with multiple myeloma off-therapy, were maintained in a one-stage long-term liquid culture system. The data indicate that: (1) blood-derived granulopoietic proliferation can be sustained for up to 8 weeks with generation of CFU-GM in a way similar to bone marrow cells; and (2) this normal hematopoiesis can be sustained in spite of the absence of any development of a substantial stromal adherent layer, which suggests that, unlike hematopoiesis from bone marrow, the blood-derived non-adherent cell population is a self-sustaining compartment. While autologous transplantation with peripheral progenitor cells is gaining importance as an alternative to autologous bone marrow transplantation, this study suggests that circulating progenitor cells may have a different behavior from marrow cells. This observation may be relevant to the understanding of cases of defective hematopoietic reconstitution.

Blood Cells↗
PubMed1987

Results of treating 53 hairy cell leukemia patients with alpha-interferon.

Fifty-three hairy cell leukemia patients were treated with low dose recombinant and natural alpha-interferon for 7 or 13 months with a marked improvement in peripheral blood and bone marrow findings. Our results suggest that daily injections have no advantage over three weekly injections, but longer treatment (12-13 months) is better than shorter treatment (6-7 months). The possibility of a relapse raises the issue of the place of splenectomy in the treatment strategy. Since the definition of remission and of relapse is based on the histological changes in the bone marrow, the necessity for the quantification of the hairy cell infiltration on bone marrow sections is stressed.

Dose-Response Relationship, Drug↗