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Biomedical subjects

B Serrou

Publications and source records attributed to B Serrou.

At least 19 recordsLinked to original sources

[Ultradian variations of interleukin-1 beta concentration (IL-1 beta), interferon gamma (IFN-gamma) and soluble IL-2 receptors (RIL-2) in healthy volunteers humen].

The aim of this study consisted in underlining the concentrations' evolution in time of two cytokines: IL-1 beta and IFN-gamma, as well as that of RIL-2 (soluble receptor for IL-2), in healthy volunteers. Under normal physiological conditions, these molecules are secreted in small amounts, according to a sequential chronology. Thus, 25 blood samples were carried out from each of the four subjects included in the study, one every 20 minutes, during 8 hours. Concentrations were determined with the ELISA method. Spectral analysis was carried out using the Frequencies Spectrum method (Fourier Transform of a temporal series). This method allows a rhythm search over a milited number of values, in a short interval of time, provided having enough samples. Important variabilities have been observed between all subjects sera, particularly for IL-1 beta (Range (mean +/- SD): 132 +/- 34.6 pg/ml to 250 +/- 17.5 pg/ml, one subject had low values: 2.34 +/- 0.53 pg/ml) and RIL-2 (Range: 677 +/- 175 pg/ml to 1,187 +/- 46.2 pg/ml). Furthermore, ultradian serum variations, characterized by the relation ((Cmax-Cmin)/Cmax) x 100, have been assessed for each subject and each molecule: IL-1 beta (Range: 18.9 to 92.2%), IFN-gamma (Range: 66.3 to 74.2%) and RIL-2 (Range: 11.6 to 86.3%); they might be the manifestation of a periodicity; this hypothesis has been confirmed by the spectral analysis. Thus, the concentrations' variation with time showed a periodicity (Range: 80 mn to 240 mn, the most frequent period was 160 mn (2 h 40 mn)).

Activity Cycles

Tumor-tissue and plasma concentrations of platinum during chemotherapy of non-small-cell lung cancer patients.

Tumor-tissue and plasma concentrations of platinum were studied prospectively in two groups of eight patients who were suffering from advanced non-small-cell lung cancer. Treatments including two different schedules of cisplatin administration (25 vs 100 mg/m2 on day 1) were compared. At 30 min after the beginning of the cisplatin infusion, blood samples and bronchoscopically obtained biopsy specimens were taken for determinations of platinum concentrations by means of flameless atomic absorption spectrophotometry. The procedure did not induce any complication. Total plasma platinum concentrations at 30 min were significantly lower (P less than 0.01) in patients receiving 25 mg/m2 (0.49 +/- 0.23 microgram Pt/ml) than in those receiving 100 mg/m2 (1.44 +/- 0.62 micrograms Pt/ml), whereas no significant difference was observed in tumor-tissue platinum concentrations (22.49 +/- 53.89 ng Pt/mg in patients receiving 25 mg/m2 vs 51.13 +/- 65.52 ng Pt/mg in those receiving 100 mg/m2). There was a weak correlation between simultaneous plasma and tumor-tissue platinum concentrations at 30 min. Tumor-tissue platinum concentrations seem to be poorly influenced by the cisplatin dose. This finding suggests a great interindividual variability of platinum tumor-diffusion properties in non-small-cell lung cancer.

Adult

The efficacy of granisetron as a prophylactic anti-emetic and intervention agent in high-dose cisplatin-induced emesis.

A single-centre, double-blind, placebo-controlled study was carried out in 28 patients with malignant disease, naive to chemotherapy, receiving cisplatin at a mean dose in excess of 80 mg/m2. Patients were randomized into two groups, receiving either granisetron (40 micrograms/kg) or placebo. Patients in both groups who experienced symptoms of vomiting and nausea were given up to a further three 40 micrograms/kg doses of granisetron on an open-label basis, allowing the assessment of granisetron as an intervention anti-emetic in the placebo group. Following granisetron administration, 13 (93%) patients had no vomiting or nausea in the first 24 h, a significant difference compared with the one patient in the placebo group who remained free from vomiting and had only mild nausea in the same period (P less than 0.001). As a single intervention agent, granisetron achieved control or improvement of existing symptoms in the remaining members of the placebo group.

Adult

[Prevention of cisplatin nephrotoxicity in cancer: adjusting the dosage with a computerized chrono-pump].

Platinum and its derivates are particularly efficient in treatment of ovarian and testis carcinomas. Nevertheless, the high nephrotoxicity of these drugs limits their use. It is known that nephrotoxicity appears when platinum plasmatic concentrations are higher than 1.5 mg/l. Moreover, the wide variability between patients and between cures, emphasizes the difficulties of utilization. Using a computerized pump and a program for individual dosage regimen, an efficient prevention of plasmatic overdosages have been realised and nephrotoxicity accidents have been avoided.

Aged

Solubilization of a human lymphocyte factor for autorosette.

With incubation at 45 degrees C, human peripheral blood lymphocytes (PBL) loose 80% of their capacity to form 1-hr autorosettes (AR). However, the addition of supernatant from heated lymphocytes (SHL) restores 93% of their rosette-forming capacity, while producing an inhibitory effect on nonincubated lymphocytes. A soluble factor present in SHL is active to a 1/5000 dilution; is absorbable on autologous red blood cells but not on sheep red blood cells; is RNase and DNase resistant and sensitive to trypsin and pronase; and acts variably on allogenic cells.

Animals

Human autologous rosettes. IV. Their relation with interleukin 2 activity production and natural killer cells in cancer patients.

Peripheral blood lymphocytes (PBL) of solid-tumor-bearing cancer patients produced a lower interleukin 2 (IL-2) activity after lectin stimulation than did those from normal subjects. Moreover natural killer (NK) cell activity and autologous rosette forming (ARF) cell rate are found significantly correlated with IL-2 production in these patients. No direct relation is observed between ARF cell ratio and NK cell activity in a given patient. A central role for IL-2 in cancer patient immune dysfunctions is suggested. Two lines of pathogenetic mechanisms are documented. First, PBL exhibited cellular function defects, namely, autologous receptor expression, IL-2 production, and NK activity. Second, these dysfunctions involved, at least partly, plasma factors. The possibility of specific deficiency, (e.g., thymic factors) is not documented. Conversely it is demonstrated that patient plasma contain immunosuppressive factor(s) that block(s) IL-2 production and ARF cell expression. Involvement of ARF cell receptor in T-cell activation is discussed.

Adult

Increased sensitivity of IL2-dependent cultured T cells and enhancement of in vitro IL2 production by human lymphocytes treated with Bestatin.

Bestatin is an inhibitor of leucine aminopeptidase and aminopeptidase B which potentiates various immune functions, such as delayed hypersensitivity and antibody formation, and inhibits tumor cell growth in animal models. Our study focuses on the effect of Bestatin on interleukin 2 (IL2) sensitivity of IL2-dependent cultured T cells (CTC) and on IL2 production by human peripheral blood mononuclear cells (PBM). Bestatin (0.01 - 10 micrograms/ml) increases CTC 3H-TdR incorporation in the presence of suboptimal (low) concentrations of exogenous IL2. Bestatin alone has no mitogenic effect on CTC. This phenomenon is due to increased CTC IL2-receptors after treatment with Bestatin. Bestatin (1 - 10 micrograms/ml) also increases (1.4 - 21 fold) IL2 production by PHA-stimulated PBM. Bestatin therefore increases both IL2 sensitivity and IL2 production. This may explain the various immunopotentiating effects of Bestatin previously described.

Adjuvants, Immunologic

The role of interleukin-2 in T colony formation by human pre-T cells (pTCFC).

Human T lymphocyte colonies may be grown in agar from pre-T peripheral blood cells. Pre-T cells giving rise to these colonies represent 0.5% of the non-adherent, E rosette and Leu 1 depleted mononuclear cell subpopulation. T colony formation is induced by PHA stimulation and only if media conditioned by PHA stimulated peripheral blood lymphocytes (PHA-LCM) is added. These media contained interleukin-2 (IL-2) and T colony promoting activity (TCPA) for pre-T cells. TCPA is co-eluted with IL-2 by gel filtration with an apparent molecular weight of 18,000 daltons. Moreover, when PHA-LCM are absorbed on IL-2-dependent cultured T cells, TCPA is removed as well as IL-2. In attempt to further demonstrate the role of IL-2 in T colony formation by the pre-T cells we used the anti-Tac monoclonal antibody directed against IL-2 receptor. We demonstrated that anti-Tac inhibits T colony formation in a dose-dependent manner in pre-T cells. We conclude that IL-2 is the essential exogenous factor contained in PHA-LCM which allows pre-T cell differentiation expression and proliferation in agar medium.

Antigens, Surface

Low dose of deoxyguanosine increases IL-2 receptors of IL-2-dependent cultured T cells.

Deoxyguanosine ( dGuo ) is a purine nucleoside phosphorylase (PNP) substrate which has been shown to inhibit T lymphoblast growth, PHA-induced cell proliferation and suppressor T cell activity. Low dGuo concentrations (0.5-5 microM) increase interleukin-2 (IL-2) sensitivity of IL-2-dependent cultured T cells (CTC). dGuo alone has no direct mitogenic effect on CTC. The increased IL-2 sensitivity of CTC was more marked in the presence of low IL-2 concentrations than high ones. CTC incubated with dGuo at 37 degrees C for 24 hrs absorbed more exogenous IL-2 than control non-treated CTC. CTC incubated at 4 degrees in the presence of dGuo did not absorb any more IL-2 than control CTC. FACS analysis further showed increased Tac expression on CTC due to dGuo . These findings indicate that a 37 degrees incubation of CTC with dGuo increases the number of CTC IL-2 receptors. dGuo was not found to increase IL-2 production by PHA-stimulated PBM. Therefore, low dGuo concentrations selectively augment the sensitivity of cells responding to IL-2 by increasing IL-2 receptors.

Cells, Cultured

The role of interleukin 1 and interleukin 2 in human T colony formation.

We investigated the roles of interleukin 1 (IL1) and interleukin 2 (IL2) on T colony formation by PHA-stimulated peripheral blood lymphocytes (PBL). Purified T cells stimulated by PHA could not generate T colonies as did PBL. Media conditioned by PHA-stimulated PBL (PHA-LCM) contained IL2 and a T colony-promoting activity (TCPA) which induced T colony formation in PHA-stimulated purified T cells. IL2 and TCPA are coeluted in the same peak of 18,000 molecular weight after gel filtration chromatography. Moreover, TCPA present in the PHA-LCM could be absorbed on IL2-sensitive cells which possessed specific receptors for IL2. These results suggest that TCPA and IL2 are related entities. Monocytes or IL1 (a monokine released by activated monocytes) also induced T colony formation in purified T cells. Phorbol myristate acetate (PMA) could replace monocytes in the induction of T colony. Monocytes, IL1, or PMA are known to be crucial requirements for IL2 production by PHA-stimulated T cells. This combined with the fact that IL2 participates in T colony formation suggests that monocytes induce T colony formation through IL2 production.

Clone Cells

Diminished interleukin-2 activity production in cancer patients bearing solid tumors and its relationship with natural killer cells.

Interleukin-2 (IL-2) activity production by stimulated peripheral blood lymphocytes (PBL) from solid tumor bearing cancer patients was lower than in normal subjects. Natural-killer (NK) cell activity in the PBL of cancer patients was very significantly correlated to IL-2 activity production (P less than 0.001). These results might suggest a central role for IL-2 in the immune dysfunctions in cancer patients, and the possible use of IL-2 as an immunological response modifier in these patients.

Adult

Modulation of human T lymphocyte functions by isoprinosine.

Isoprinosine was shown to alter certain T cell functions. In vitro, it has previously been shown to induce suppressor cell activity in both mouse and human lymphocytes. Our in vitro results suggest that Isoprinosine acts on immune balance by increasing the number of non-suppressor T cells and, at least partially blocks Con A induced suppressor activity. In vitro NK activity remained unaltered.

Adjuvants, Immunologic

Induction of human T colony formation by phorbol myristate acetate.

Phorbol myristate acetate (PMA) is a potent inducer of T colony formation by peripheral blood lymphocytes. A mean cloning efficiency of 0.3% (0.05-0.5%) is obtained with PMA concentrations of 100-1000 ng/ml. PMA-induced T colony formation does not require the presence of monocytes and therefore differs from other mitogens in this respect. Purified T-colony-promoting activity (TCPA) (devoid of phytohaemagglutinin (PHA)) increases PMA-induced T colony numbers and induces T colony formation at low PMA doses (0.01 to 1 ng), concentrations at which no T colonies are detected in the absence of added TCPA. PMA-induced colonies are mainly composed of cells bearing Fc receptors for IgM (54%), which is not the case for colonies obtained with PHA (11%). PMA-induced colony cells do not bind OKT3 and OKT4 monoclonal antibodies, whereas 23% are able to bind OKT8 antibody. These results demonstrate that PMA is a potent inducer of T colony formation and may therefore serve as a useful tool for the study of T-cell differentiation.

Antigens, Surface

Human soluble Fc gamma-binding material. I. Immunochemical properties of the material produced by the T cell line KE37.

A soluble Fc gamma-binding material (S-Fc gamma BM) is produced by the Fc gamma receptor-bearing human T cell line KE37 but not by the two Fc receptor-negative cell lines Molt 4 and Reh 6. The S-Fc gamma BM has specific affinity for the Fc fragment of IgG and none for the Fab fragments. It can be obtained in radioactive form after internal labeling with radioactive amino acids. It can then be isolated from the supernatant of the KE37 cell line by affinity chromatography, gel filtration and isoelectric focusing. The subunit components of S-Fc gamma BM are 23,000-dalton polypeptide chains. The soluble form is a dimer (42,000 to 45,000 m.w., pl 6.2), which retains Fc gamma-binding activity after isolation. Higher m.w. polymers of the 23,000-dalton subunits are also present in the supernatant of the KE37 cell line. These polymers are relatively insoluble in aqueous solvents but possess Fc gamma-binding activity. The S-Fc gamma BM molecules might be derived from a membrane-inserted form by restricted proteolytic cleavage at connecting regions of a larger polypeptide chain folded into 23,000-dalton subunits.

Animals

Suppressor effect of prostaglandins on T colony formation.

This study evaluated the action of prostaglandins on T colony formation. A single step culture process was used which involved direct seeding of freshly isolated peripheral blood mononuclear cells (MC) in semi-solid agar culture medium containing phytohaemagglutinin (PHA). Suppression of endogenous production of prostaglandins with 10(-6) M indomethacin increased T colony formation by up to 100%. Similarly, addition of synthetic prostaglandin E (PGE) to the culture system demonstrated a dose-dependent reduction of T colony formation by PHA-stimulated non-adherent cells. The 50% inhibitory dose (ID 50) was 10(-7) M for PGE2 and 1.3 x 10(-7) M for PGE1. Prostaglandin F had no effect on T colony formation. The synthesis of PGE by adherent cells can be increased two- to three-fold in the presence of T colony promoting activity released by PHA-stimulated lymphocytes. We conclude that monocyte produced PGE is responsible for the suppressor effect exerted by these cells on T colony formation. The PGE inhibitory role is interpreted as a feedback mechanism, modulated by lymphokines released by PHA-activated lymphocytes.

Clone Cells

Modulation of PHA-induced T colony formation by phorbol myristic acetate.

PMA (10 ng/ml), induced a four-fold increase in PHA-induced T colony formation by peripheral blood lymphocytes (PBL). At lower (0.1-1 ng/ml) and higher concentrations (100-1,000 ng/ml), PMA had an inhibitory effect. The potent co-mitogen effect observed at 10 ng/ml PMA was associated with a strong increase in T colony promoting activity (TCPA) released by PHA stimulated PBL cultured in the presence of PMA (10 ng/ml). PMA at all concentrations exerted an inhibitory effect on T colony formation when PBL were cultured in the presence of PHA and an optimal concentration of exogenous TCPA. PMA was also capable of assuming the essential role played by monocytes in T colony formation. Thus, PMA can fulfil both co-mitogen and monocyte like roles in T colony formation. These activities closely resemble those previously described for interleukin 2 (IL2) production.

Clone Cells