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C Jasmin

Publications and source records attributed to C Jasmin.

At least 19 recordsLinked to original sources
PubMed1992

Purification and identification of a CD25 expression inhibitory protein from cell-free supernatants of chronically HIV-infected promonocytic cells.

The CD25 (IL-2-R alpha) cell surface glycoprotein expressed transiently during T-cell activation is implicated in the high affinity IL-2 receptor. This paper shows that cell-free supernatants from chronically HIV-infected promonocytic cells spontaneously produce a soluble factor which inhibits CD25 expression on PHA-activated human PBMC. We purified the CD25 expression inhibitory activity by a factor 12,350, using XM50 ultrafiltration, Superose 12 molecular sieving chromatography and MonoQ anion-exchange chromatography. Then we associated this activity to one single spot (M(r) 29,000, pI 6.8) on an O'Farrell two-dimensional gel. Our data demonstrate that this protein (M(r) 29,000, pI 6.8) is released from HIV-infected promonocytic cells and suggest that this factor is a new monokine regulating the T-cell activation process.

Cell Line↗
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

Inhibition of human immunodeficiency virus (HIV) type 1 multiplication by an avian cellular factor.

A factor secreted from avian cells infected non productively with a non cytopathogenic mutant of vesicular stomatitis virus (VSV ts 1026) interferes with HIV replication in CEM cells and peripheral blood monocytes (PBL). Production of infectious particles is decreased and many virions lack cores and/or spikes. In CEM cells the prmRNA is spliced into 7.5, 4, and 2 kb mRNA. Residual virus contains less env encoded proteins and p 18; p 25 appears as several bands. The processing of tat, rev. and nef proteins differs in treated cells and in controls.

Animals↗
PubMed1992

Abnormal expression of IL-2R beta (p70)-binding polypeptide on HIV-infected patients' cells.

The constitutively expressed IL-2R beta (p70) chain participates in the formation of high-affinity (h.a.) IL-2R and transduces IL-2-mediated signals to normal cells. Its expression on HIV-infected patients' PBMC was evaluated and was found to be decreased in both nonstimulated CD4+ and CD8+ cells. Mitogenic cell stimulation induced IL-2R beta chain expression on both CD4+ and CD8+ cells from asymptomatic and persistent generalized lymphadenopathy patients but not on those from AIDS patients. Comparison of mean fluorescence intensity of IL-2R beta positively stained cells from normals and patients did not reveal significant differences. Cross-linking of 125I-rIL-2 on patients' PHA-blasts revealed decreased signals corresponding to both IL-2-binding chains and, in some cases, neither IL-2R alpha nor IL-2R beta chains could be detected. Decreased expression of IL-2R beta polypeptide was associated with impaired accumulation of the corresponding mRNA transcripts. Binding experiments with 125I-rIL-2 under h.a. conditions showed a decreased number of IL-2-binding sites/cell which was more pronounced in patients with AIDS than in patients with less advanced clinical stages. In vitro HIV infection of normal PHA-blasts also resulted in a decreased number of h.a. IL-2R/cell. High concentrations of rIL-2 in the absence of other mitogenic stimuli induced a decreased cell proliferation and expression of the IL-2R alpha chain and did not enhance the constitutive NK and the generation of LAK activity in several patients, suggesting an impaired IL-2R beta chain-mediated cell activation.

Antibodies, Monoclonal↗
PubMed1992

A phase II study of sequential recombinant interleukin-2 followed by dacarbazine in metastatic melanoma.

16 patients with disseminated malignant melanoma (1 with primary ocular melanoma) entered a multicentre phase II study of recombinant interleukin-2, (rIL-2) given by continuous intravenous infusion on days 1-5 at 18 x 10(6) IU/m2 per day, followed by dacarbazine 850 mg/m2 on day 8. After a 2 week rest, a second course was given. In the absence of disease progression, monthly maintenance cycles were given for up to four cycles. 16 patients received one cycle, 14 received two and 6 patients three or more. All 16 patients are evaluable for toxicity and 15 for response. 2 patients responded (13%). 1 patient with lung and pleural metastases achieved partial remission after two cycles and went off treatment after six cycles. 3 months later a complete response was noted lasting 396+ days. A second patient with lung metastases had a partial response lasting 153 days. 3 patients (20%) had stable disease. Mean rebound lymphocytosis (24-48 h after the end of rIL-2 therapy), cell count 4.9 x 10(9)/l (2.6-8.8 x 10(9)/l) was within the expected limits. Other toxicity was as expected. Thus sequential treatment with rIL-2 and dacarbazine is feasible but synergy did not occur.

Adult↗
PubMed1992

Expression of the interleukin-2 receptor on human fibroblasts and its biological significance.

In this study, we have investigated the expression of the alpha and beta chains of the IL-2 receptor (IL-2R alpha, IL-2R beta) both at the membrane and at transcriptional levels during the lifespan of human embryonic fibroblasts. Here we show that the mAbs IOT14 and MIK beta 1 directed against the IL-2 binding sites of the IL-2R alpha and IL-2R beta respectively, stain human embryonic fibroblasts early in their life span. Data from [125I]rIL2 cross-linking experiments show the simultaneous expression of two IL-2 binding peptides of 70 and 55 kDa respectively on embryonic young fibroblasts as on lymphoid activated cells. The p55 and the p70 IL-2 binding peptides are shown to be specific for the IL-2R alpha and to the IL-2R beta by the finding that these bands are abolished by excess amounts of cold IL-2 and mAbs directed against the IL-2 binding sites of the alpha and beta chains. Scatchard analysis after [125I]IL-2 labelling shows the presence of both high affinity (150 sites with a Kd of 147 pM) and low affinity (1100 sites with a Kd of 4 nM) IL-2 binding sites. Northern blot and dot blot analysis show the presence of specific transcripts for the IL-2R alpha and IL-2R beta genes in early passaged fibroblasts. By contrast, in senescent cultures, only the IL-2R beta transcript were detected. Finally, IL-2 at low concentrations (36 pM) down modulates the level of the intercellular adhesion molecule ICAM-1 in young but not in senescent cultures.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Adhesion Molecules↗
PubMed1992

Phase I trial of recombinant interleukin-2 followed by recombinant tumor necrosis factor in patients with metastatic cancer.

In this Phase I trial, the feasibility of sequential administration of continuous intravenous recombinant interleukin-2 (rIL-2) at 18 x 10(6) IU/m2/day for 6 days, followed by three daily bolus intravenous recombinant tumor necrosis factor (rTNF) infusions at doses escalating between 10 and 120 micrograms/m2/day, was investigated in 31 patients with metastatic malignancies. Prophylactic use of indomethacin prior to and during rTNF administration was found to significantly reduce toxicity. However, despite prophylactic indomethacin, a maximum tolerated dose of rTNF of 120 micrograms/m2 was reached. The limiting toxicity was hypotension. Predictable flu-like toxicities (i.e., fever/chills, hypotension, gastrointestinal toxicity, edema, malaise) were seen in most patients. These started during the rIL-2 infusion and continued during rTNF administration, particularly in the absence of indomethacin. Hematological, renal, and hepatic toxicities were not dose limiting. These toxicities were all reversible after treatment interruption. Pulmonary toxicity [i.e., anaphylactic-like reactions, bronchospasms, and adult respiratory distress syndrome (ARDS)] was seen in several patients immediately after rTNF infusions, irrespective of the rTNF dose or treatment cycle, and mainly in patients with extensive pulmonary metastases. The combined effect of treatment-related ARDS, lung metastases, and a Guillain-Barré syndrome led to the death of one patient. Two partial responses were seen in this study (i.e., breast and renal cancer). Based on these results, a Phase II trial of rIL-2 followed by rTNF has been initiated in metastatic breast cancer patients.

Adolescent↗
PubMed1992

Human immunodeficiency virus-infected adherent cell-derived inhibitory factor (p29) inhibits normal T cell proliferation through decreased expression of high affinity interleukin-2 receptors and production of interleukin-2.

Adherent cells from HIV-infected subjects as well as in vitro HIV-infected normal adherent cells produce spontaneously a 29-kD (p29) factor that inhibits mitogen-induced proliferation of normal T cells. p29 mediates a partial dose-dependent inhibition of total protein synthesis in both nonstimulated and PHA-activated cells that is associated with impaired PHA-induced expression of IL-2 receptor (IL-2R)alpha chain, HLA-class II molecules, and production of IL-2 by these cells; conversely, p29 does not modify the expression of IL-2R beta chain, 4F2, CD9, or transferrin receptor, or the production of IL-1 and TNF alpha by the cells. 1 h preincubation of the cells with p29 is sufficient to detect its biologic activity and added rIL-2 abrogates p29-induced inhibition of IL-2R alpha chain expression; however, p29 does not display any biologic effect on already expressed IL-2R alpha chains. The impaired expression of IL-2R alpha chain mediated by p29 is not due to a decreased accumulation of the corresponding mRNA transcripts, but is associated with a two-fold increase of intracellular cAMP. Binding experiments with 125I-rIL-2 reveals that p29 induces a 50% decrease in the number of both high and low affinity IL-2R per cell. p29 also inhibits alloantigen-induced proliferation of PBMC, whereas it does not modify IL-2-dependent proliferation of 48-h PHA-blasts that already express high affinity IL-2R. These findings indicate that p29 mediates its biologic activity during early stages of T cell activation affecting the expression of high affinity IL-2R and production of IL-2, through a nontranscriptional mechanism involving an increase of intracellular cAMP.

Cyclic AMP↗
PubMed1992

Increased synthesis of extracellular spleen glycosaminoglycans in an experimental myeloproliferative syndrome.

The changes occurring in the hematopoietic extracellular matrix in an experimental myeloproliferative syndrome were explored by comparing the glycosaminoglycan (GAG) composition of normal mouse spleens and spleens infected with myeloproliferative sarcoma virus (MPSV). Large quantities of hyaluronate and of sulfated GAGs accumulated in the extracellular matrix of infected spleens, as shown by histoimmunoassay and alcian blue staining, respectively. The splenic GAGs were either labeled with 35S-sulfate injected in vivo or unlabeled. The spleens were fractionated to separate hematopoietic cells from the stromal component containing extracellular matrix material and fibroblasts, and the GAGs were extracted from each fraction. Specific degradative treatments and electrophoresis indicated that sulfated GAGs were mostly chondroitin sulfate and heparan sulfate. Three hours after in vivo injection of 35S-sulfate, the amount of 35S-GAGs was increased approximately fivefold per mg stromal proteins. The bulk of these 35S-GAGs (70%) was recovered in the stromal fraction. The higher amount of sulfated GAGs in leukemic spleen was due both to the presence of more producer cells (infected fibroblasts and hematopoietic cells) and to a stimulation of GAG synthesis per cell, as evidenced 35S-labeling in in vitro experiments. Chondroitin sulfate was the main sulfated GAG present in the culture medium of both hematopoietic and fibroblastic cells and in the pericellular material released by trypsin from fibroblastic cells. High amounts of chondroitin sulfate, which has a possible role in the detachment of hematopoietic cells from the stromal cells, may favour the release of hematopoietic cells from the spleen into the peripheral blood. Heparan sulfate was produced by fibroblastic cells and it was principally present in their pericellular material. Considering the capacity of heparan sulfate to retain cytokines, as demonstrated by others in vitro, large amounts of heparan sulfate may result in the retention of large amounts of the cytokines, which production is enhanced in the infected spleen. This phenomenon may contribute to promote the hematopoietic stem cell proliferation characteristic of the MPSV-induced myeloproliferative disease.

Animals↗
PubMed1992

Open trial of tacrine therapy in 70 HIV-infected patients.

The purpose of this study consisted in following-up the biological and clinical parameters in HIV infected patients treated with tacrine (THA). THA (150-300 mg/d) was administrated to 70 patients (39 IVC I and 31 IVC II and III). Thirty-five were treated after discontinuation of AZT treatment and 35 as a first intention treatment. Thirty (43%) patients showed an increase in the CD4+ cell count by more than 50% relative to pretreatment levels and fifteen (21%) showed an increase of more than 25%. p24 antigenemia (Ag p24) became negative in eight of the twenty-seven patients who were initially positive, and decreased by 25 and 50% in nine and six patients, respectively. Ag p24 was therefore decreased in 80% of the patients. From a clinical point of view, there were two deaths (3%) and five opportunistic infections (7%). The treatment with THA was stopped in five patients because of side effects (nausea, rash). Neither hepatotoxicity, hematotoxicity, nor pancreatitis was observed during the THA treatment. In group II and III only two patients (6%) developed an opportunistic infection.

AIDS-Related Opportunistic Infections↗
PubMed1992

Interleukin 2 production and interleukin 2 receptor expression by human immature leukemic T cells.

In order to determine the role of interleukin 2 (IL2) on the proliferation of leukemic cells from patients with T-cell acute lymphoblastic leukemia (T-ALL) we studied the production of IL2, the function of IL2 receptors (IL2R) expressed on T-ALL cells and their IL-2-dependent in vitro proliferation. Leukemic cells from six out of 17 T-ALL/T-cell non-Hodgkin's lymphoma patients with a prothymocyte (stage I) or a mature thymocyte (stage III), but not with a common thymocyte (stage II) phenotype, could proliferate, in a dose-dependent manner, in response to recombinant IL2 (rIL2) and anti-Tac and TU27 moAbs as well as polyclonal anti-IL2 purified immunoglobulin G could inhibit this IL2-induced cell proliferation. Both crude or/and Amicon-concentrated media conditioned by T-ALL cells from 10 out of 13 tested patients contained IL2 activity as assessed by colorimetric biological and immunoenzymatic assays; this biologic activity was due to a 14.5 kDa molecule adsorbed by anti-IL2 antibodies in an immunoaffinity assay. Although less than 10% of fresh leukemic cells expressed IL2R alpha (Tac) chain, a 24 h cell incubation in the absence of any mitogenic stimulation induced IL2R alpha chain expression in five out of 13 patients (11-83% Tac+ cells). Morever, Tac mRNA transcripts could be detected in fresh cells from all 10 patients tested. Staining of fresh leukemic cells with an IL-2R beta-chain-specific monoclonal antibody and flow cytometry analysis revealed that 4-13% of leukemic cells were positive. Binding experiments with 125I-rIL2 showed a small number of high affinity IL2R on fresh cells from three T-ALL patients (114-200 sites/cell, dissociation constant = 101-181 pm). Finally, antibodies against IL2R alpha, IL2R beta and IL2 could inhibit both IL2 driven and spontaneous cell proliferation of most patients' T-ALL cells, although in some cases an heterogenous pattern of inhibition was observed. Taken together, these findings strongly suggest that an IL2/IL2R-dependent mechanism could be involved in the proliferation of some T-ALL cells.

Antigens, CD↗
PubMed1992

Phorbol myristate acetate-induced expression of high-affinity interleukin 2 receptors and production of interleukin 2 by human acute lymphoblastic leukemia T cells.

The effect of phorbol myristate acetate (PMA) on the expression of interleukin 2 receptors (IL-2R), production of IL-2 and IL-2-dependent proliferation of acute lymphoblastic leukemia T cells (T-ALL cells) from 10 patients was studied. First, the effect of PMA on the expression of cell surface markers was assessed: a decrease of CD3 and CD4, and an enhanced expression of CD8 molecule were observed on T-ALL cells. Moreover, PMA exhibited an heterogenous effect on various activation-associated molecules such as a decreased expression of transferrin receptor and T10 molecule and an induced expression of 4F2 and CD9 molecules. It is known that functional high-affinity IL-2R are composed of at least two IL2 binding molecules, the alpha (p55) and beta (p70) chains. We found that PMA induced the expression of both IL-2R alpha and IL-2R beta chains, as well as IL-2 production by T-ALL cells. These effects were time- and dose-dependent. Cross-linking experiments with 125I-labelled recombinant IL-2 (125I-rIL-2) revealed both p55 (IL-R alpha) and p70 (IL-2R beta) IL-2-binding polypeptides, whereas binding equilibrium assays on PMA-treated cells demonstrated the presence of a low number (31-413) of high-affinity binding sites/cell in five out of six cases analysed, as well as intermediate affinity IL-2R (1234-3919 sites/cell) in four out of six cases, according to the time of incubation with PMA. In two cases tested high-affinity IL-2R on PMA-treated T-ALL cells could internalize 125I-rIL-2 at 37 degrees C. PMA alone enhanced the spontaneous proliferation of T-ALL cells in three cases, whereas a clear synergy between IL-2 and PMA could be detected in three patients' cells. Moreover, exogenous rIL-2 enhanced cell proliferation of PMA-preincubated T-ALL cells in four cases studied. Taken together, these observations indicate that a short-term incubation of T-ALL cells with PMA can activate the IL-2/IL-2R system on these cells without inducing strong modifications of their differentiation status. These results thus suggest that this system may be involved in the proliferation process of some activated immature T cells.

Cell Division↗
PubMed1991

[Human interferons: biological and clinical promises and premises].

Interferons have been demonstrated by animal experimentation to have antiviral, antitumoral and immune effects. Clinical trials of human recombinant alpha-interferon have shown a substantial therapeutic effect in various chronic leukemias and lymphomas. Studies concerning the mechanisms of the anti-leukemia effect of the various interferons have demonstrated that they play an important role in regulating the proliferation of normal and leukemic cells. These lymphokines interact with other important biological mediators such as interleukins, growth factors, factors associated with angiogenesis, etc. New therapeutic developments in oncology and in immunopathology may be expected in the near future.

Adjuvants, Immunologic↗
PubMed1991

Recombinant interleukin-2 in metastatic renal cell carcinoma--a European multicentre phase II study.

This multinational, multicentre study represents the introduction of recombinant interleukin-2 (rIL-2) in Europe. From December 1987 to June 1989, 57 eligible patients with metastatic renal cell cancer were treated with rIL-2 administered as continuous intravenous infusion. 8 out of 51 evaluable patients responded (16%), 2 complete remission (CR) and 6 partial remission (PR). 10 patients had no change (20%). The response duration for CR was 209 and 394+ days. The median response duration for PR was 371 (range 140-506+) days. Dose-limiting grade 3-4 toxicities were hypotension in 52% of the patients, arrhythmia (4%), dyspnoea (8%), creatinine rise (4%), peripheral neurotoxicity (10%) and central neurotoxicity (10%). Toxicities most often recovered solely on interrupted therapy. 2 patients died due to catheter-related septicaemia and one patient died of rIL-2 induced renal failure. The study confirmed the antitumour efficacy of rIL-2 in renal cell cancer. Toxicities were numerous, but manageable by close observation in a normal oncology ward without routine use of an intensive care unit.

Adult↗
PubMed1991

20 alpha-hydroxysteroid dehydrogenase expression in a murine virus-induced myeloproliferative syndrome.

The myeloproliferative sarcoma virus (MPSV) infection in DBA/2 mice leads to important quantitative and qualitative changes in their hemopoiesis. These findings suggest a disturbance in the production and action of a certain hemopoietic factor similar to IL3. Here, we show that the level of the 20 alpha-hydroxysteroid dehydrogenase (20 alpha-SDH) expression, which can be induced by IL3, is dramatically increased in spleen and thymus of MPSV-infected mice. Our results suggest that quantification of 20 alpha-SDH activity can be used to indicate abnormal production of a growth factor similar to IL3 in hemopoietic system diseases.

20-Hydroxysteroid Dehydrogenases↗
PubMed1991

Concepts of remission, curability and lineage involvement in relationship to the problems of minimal residual leukaemia.

Minimal residual leukaemia (MRL) is due to chemotherapeutic failure. Chemoincurability in chronic myeloid leukaemia and in myelodysplastic syndrome is the norm and is the result of tumour defect arising within the marrow stem cell compartment. We propose that this is indeed the state of affairs in the majority of adult acute leukaemias and such tumours derived from stem cells are chemoincurable. The proportion of acute leukaemias which belong to this category can only be cured by allogeneic bone marrow transplantation though conventional chemotherapy and autotransplant may result in prolonged periods of remission and a return to a preleukaemic state in some patients. A proportion of the acute leukaemias occurring predominantly in children are presently curable by chemotherapy. It is hypothesized that these chemocurable leukaemias derive from the compartment of haemopoietic progenitors already irreversibly committed to a single lineage. Some recent studies using markers of the leukaemic clone to determine the origin of in vitro myeloid colony forming cells support this concept. Intrinsic and/or acquired genetic chemoresistance represents a supplementary restriction to the chemocurability of acute leukaemias. New methods of detecting MRL are sensitive enough to detect up to one leukaemic cell in 10(6) bone marrow mononuclear cells. However, it is possible that even such sensitive techniques will not be sufficient to determine whether patients in complete remission continue to harbour leukaemic cells in the stem cell compartment when the marker of interest might not be expressed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗