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Biomedical subjects

E Legrand

Publications and source records attributed to E Legrand.

At least 91 records · Page 5Linked to original sources

[Characteristics and mechanisms of action of leukocyte depletion filters].

Since their creation, leukocyte depletion filters, used to prepare leukocyte-poor red cell or platelet concentrates, have been continuously evoluting: their volume has been reduced and their composition has been modified, polyester fibers have replaced cotton wool or cellulose acetate. In the same way, their capacity to remove leukocytes has increased. The mechanisms of cell separation are still unclear. Through published studies, different factors seem to be implicated, such as wetable surface of the filter, surface tension or charge density of fibers. It was also observed that removal of lymphocytes from red cell concentrates is rather based on trapping in the fiber network, and that removal of granulocytes, monocytes and platelets is partly due to activation and subsequent adhesion to the fibers. There have been few studies of the mechanism of leukocytes depletion from platelets concentrates.

Adsorption↗

[Polycythemia after kidney transplantation].

Between 1971 and 1990, 251 kidney transplanted patients with a well functioning graft were evaluated to determine the frequency of post-transplant erythrocytosis (PTE). Thirty-one patients (13 percent) developed polycythaemia 10.6 +/- 10 months after transplantation. Thromboembolic complications occurred in 22 percent of the cases. The frequency of PTE was higher in males than in females (sex ratio: 7.2 vs 2.1; P < 0.05). Patients with renal dysplasia had a lower incidence of PTE (3 vs 22 percent; P < 0.05) as did those who had been treated with azathioprine (9.4 vs 19 percent; P < 0.05). None of the patients treated with recombinant erythropoietin before transplantation developed PTE during a mean follow-up of 15.1 +/- 4.5 months. The majority of polycythaemic patients had normal erythropoietin levels. These results show that there is an erythropoietin-independent proliferation due to an increased sensitivity of erythroid progenitors or to an erythroid stem cell stimulation by cytokines.

Adult↗

Acamprosate modulates synaptosomal GABA transmission in chronically alcoholised rats.

Male Sprague-Dawley rats were pulmonary alcoholised for 30 days. Six were treated with acamprosate (400 mg/kg/day, PO) during alcoholisation. The control nonalcoholised group also received acamprosate (400 mg/kg/day, PO) during the 30 days. At the end of the experiment, brains areas (cortex, hippocampus, thalamus, striatum, and olfactory bulbs) were dissected for the study of synaptosomal 3H-GABA uptake. In another experiment, GABA levels were determined in the same areas using HPLC with electrochemical detection. Blood ethanol levels were also measured during alcoholisation. Acamprosate treatment did not modify blood ethanol levels. In cortex and olfactory bulbs, alcoholisation increased 3H-GABA uptake (Vmax) with an increase in the affinity (Km). 3H-GABA uptake was not affected by alcoholisation in other brain areas. In hippocampus and thalamus, acamprosate treatment enhanced 3H-GABA uptake (Vmax) only in alcoholised rats. Moreover, in thalamus, alcoholisation enhanced GABA levels. The effect of alcohol and acamprosate on GABA presynaptic events is discussed and it is concluded that the action of ethanol and acamprosate on GABA transport could be, in part, responsible for the modulation by acamprosate treatment of ethanol behaviour.

Acamprosate↗

DPB1 polymorphism in rheumatoid arthritis: evidence of an association with allele DPB1 0401.

HLA-DP polymorphism was examined in 71 rheumatoid arthritis patients and 148 controls, using dot-blot analysis with 14 synthetic oligonucleotide probes specific for the variable region of the DPB1 second exon. The DPB1 0401 allele was found to be significantly more frequent in RA patients than in controls (77.46% vs 55.40%, p less than 0.002, pc less than 0.03, relative risk value: 2.74). An association between DPB1 0401 and seropositivity for rhumatoid factors was also observed: 44 of the 55 seropositive RA patients were DPB1 0401 (p less than 0.001). Analyzing the HLA DPB1 alleles frequencies in 57 HLA-DR-typed RA patients did not show any linkage between the DPB1 0401 and the DR4 specificities. Furthermore, the DPB1 0401 homozygous frequency was increased in DR4-negative RA patients. Our findings suggest an independent role of the DPB1 0401 allele in the genetic susceptibility to RA.

Adult↗

[Real effects of sport on the bone mass in women].

What is the role of physical training in the prevention of osteoporosis? The authors tried to answer the question, comparing the positive and negative effects of exercise on women bone mass before and after the menopause and proposed a way of management of bone loss in amenorrheic women athletes.

Amenorrhea↗

Tianeptine, a specific serotonin uptake enhancer, decreases ethanol intake in rats.

The effect on ethanol intake of the selective 5-HT uptake enhancer tianeptine was examined in rats and compared with that of fluoxetine, a specific 5-HT uptake inhibitor. Both treatments significantly decreased ethanol intake (54% by tianeptine and 57% by fluoxetine). Fluoxetine also decreased food intake whereas tianeptine did not. Body weight was decreased by 12.5% in fluoxetine-treated rats but was not modified by tianeptine. It is proposed that tianeptine has a specific action on ethanol intake, possibly related to its effect on serotonin function.

Alcohol Drinking↗

Ethanol intake and 3H-serotonin uptake I: A study in Fawn-Hooded rats.

Ethanol intake and synaptosomal 3H-serotonin uptake were studied in male Fawn-Hooded and Sprague-Dawley rats. Fawn-Hooded rats consumed more alcohol and more water than Sprague-Dawley rats. Plasma alcohol levels of Sprague-Dawley rats were not detectable but were about 5 mg/dl in Fawn-Hooded rats. Ethanol intake increased the Vmax of serotonin uptake in Fawn-Hooded rats in hippocampus and cortex, but not in thalamus. In Fawn-Hooded rats, serotonin uptake (Vmax) was higher than in Sprague-Dawley rats cortex. Ethanol intake reduced the Vmax of serotonin uptake in Fawn-Hooded rats in hippocampus and cortex. In cortex, the carrier affinity for serotonin was increased in alcoholized Fawn-Hooded rats. These results indicate that synaptosomal 3H-serotonin uptake is affected by ethanol intake. In Fawn-Hooded rats, high ethanol consumption is associated with high serotonin uptake. In rats presenting high serotonin uptake, alcoholisation reduces 3H-serotonin internalisation in synaptosomes, indicating a specific sensitivity to alcohol intake of serotonin uptake system.

Analysis of Variance↗

Ethanol intake and 3H-serotonin uptake. II: A study in alcoholic patients using platelets 3H-paroxetine binding.

The kinetic parameters of 3H-paroxetine binding and 3H-serotonin uptake were studied in platelets of alcoholic patients. There was no difference between alcoholic and non alcoholic subjects in 3H-paroxetine binding. When binding and 3H-serotonin uptake were studied, in the same plasma of the same subjects, the Vmax of serotonin uptake was increased in alcoholics. The data confirm the involvement of serotonin uptake system in alcohol dependence and suggest that serotonin uptake and paroxetine binding sites may be regulated independently in this pathology.

Adult↗

A new leukemogenic retrovirus isolated from tumor cells derived from a radio-induced lymphoma of C57BL/6 mice: analysis of the env and LTR sequences.

We report the cloning and characterization of a new ecotropic provirus encountered in a radio-induced thymic lymphoma of the C57BL/6 mouse. The provirus with an abnormally long LTR was inserted in the chromosomal DNA within the Pvt-1/MLVi-1/Mis-1 region which is a common integration site for MCF virus in mice and for Mo-MuLV in rats. This new ecotropic provirus was molecularly cloned and found to be infectious and competent for replication after transfection of murine cells. The recovered virus termed T3651/B was B-ecotropic, T-lymphotropic (in vivo) and highly leukemogenic for newborn C57BL/6 mice and for adult mice provided they were submitted to a subleukemogenic dose of irradiation. As compared to the AKV prototype N-ecotropic endogenous retrovirus, the T3651/B env proteins are only affected by few scattered point mutations. In contrast, the LTR has five repeats of enhancer sequences containing consensus motifs specific of the nuclear factors NF1-like, LVa, LVb and SEF1. Since a virus with such properties was encountered only once in 31 radio-induced tumors and isolated at a fourth tumor passage, a direct role of T3651/B virus in tumor genesis after irradiation is uncertain. Nevertheless, it is clear that T3651/B virus is a new leukemogenic retrovirus with a particular LTR structure which fits well with the model proposed by Rassart et al. (J. Virol. 58, 96-106, 1986) for the emergence of a thymotropic highly leukemogenic RadLV.

Amino Acid Sequence↗

Production of interleukin 3 by spleen cells in immunodeficient C57BL/6 mice after injection of RadLV-Rs viral complex.

Injection of RadLV-Rs viral complex to C57BL/6 mice results in massive enlargement of lymphoid organs. The polyclonal T and B populations which proliferate in spleen and lymph nodes display severely impaired immune functions. Several data suggest that development of this immunodeficiency syndrome is dependent on the presence of T cells whose functions are progressively altered. In contrast, the erythro-myeloid populations and the stem cell compartment are not deeply modified, suggesting that the production of the lymphokines involved in their regulation is not altered. Interleukin 3 (IL-3) is mainly involved in this regulation. Thus, the purpose of the present experiment was to evaluate the IL-3 production: in RadLV-Rs injected mice IL-3 production is decreased at the cellular level but if it is evaluated by taking into account the increase of spleen cellularity, it is initially decreased and later on, above the normal value.

Animals↗

Effect of interleukins and anti-CD3 monoclonal antibody on the proliferation of thymocytes from irradiated mice.

The responsiveness of thymocytes on day 8 after irradiation to mitogens or anti-CD3 monoclonal antibody was evaluated in the presence of interleukin 2 (IL-2), interleukin 4 (IL-4), interleukin 6 (IL-6) or phorbol-myristate-acetate (PMA). After irradiation, the thymocytes were poorly responsive to T cell mitogens (Concanavalin A, phytohemagglutinin) and the defect could not be overcome by exogenous IL-2, IL-4, IL-6 or by PMA. In contrast, the combination of the calcium ionophore (A23187) and PMA stimulated thymocyte proliferation to a normal level. The anti-CD3 antibody associated with PMA activated thymocytes above the control values, but this was not observed when anti-CD3 was associated with either IL-2 or IL-4. These results suggest that in the thymic populations present early after irradiation 1) the weak proliferative response to mitogens could be related to a defect at a thymocyte level associated or not to an accessory cell deficiency, 2) the intracellular mechanisms involved in T cell proliferation were not altered, 3) the T cell antigen-receptor/CD3 complex was functional.

Animals↗

Natural killer activity, production of interferon-gamma and interleukin 2 in immunodeficient C57BL/6 mice injected with RadLV-Rs viral complex.

Injection of the RadLV-Rs, a viral complex originally obtained from radio-induced thymic lymphosarcomas, into C57BL/6 mice induces a massive enlargement of spleen and lymph nodes. T- and B cell-proliferating populations display severe deterioration of their immune functions, resulting in death of the animals within three months. In contrast, the experiments reported here indicate that in such animals the natural killer (NK) activity is increased for about 2 months after viral injection. Interleukin 2 production is dramatically decreased, whereas interferon-gamma production is increased to twice the control value and thereafter decreases concomitantly with NK activity. This suggests that in RadLV-Rs-injected mice, the high NK activity is related to interferon-gamma production.

Acquired Immunodeficiency Syndrome↗

Identification of malignant cell clones in radio-induced murine thymic lymphomas by viral and cellular probes.

The role of B ecotropic recombinant retroviruses in the emergence and the progression of radio-induced thymic lymphomas was evaluated by analyzing the cell populations present in nine primary and in in vivo propagated tumors. For this, tumor DNAs were analyzed by the Southern method using probes specific for newly acquired proviral sequences, T-cell receptor beta-chain, and immunoglobulin heavy chain genes. Our results show that primary radio-induced tumors are composed of several tumoral cell clones but do not support that malignant cell transformation and proliferation are conferred, solely, by the newly acquired ecotropic recombinant retroviral sequences.

Animals↗

Production of cytokines after lipopolysaccharide stimulation of murine spleen cells during lymphoma development in AKR mice.

Injection of syngeneic lymphoma cells in AKR mice, resulted in an important increase of splenic natural killer (NK) activity in the early days following the graft. Modifications of the production of different types of cytokine: interferon, interleukins 1 and 2, tumor necrosis factor (IFN, IL-1, IL-2, TNF), involved in the regulation of NK activity, were investigated in short-term cultures of total, adherent and non-adherent fractionated spleen cells, using lipopolysaccharide as the triggering or amplifying agent. Upon stimulation with lipopolysaccharide, splenocytes from lymphoma-grafted mice released a large amount of interferon as compared to controls with a maximum level 1 day after the graft. Equal amounts of IFN-gamma and IFN-alpha/beta were detected. Treatment of spleen cells prior to culture with anti-(asialo-GM1) or anti-(Thy-1.1) antibodies reduced interferon production by 80% and 50% respectively. This finding indicates that (a) the IFN-gamma is produced by Thy-1-positive cells and (b) the production of IFN-gamma by these cells is at least partially under the control of asialo-GM1-positive cells. We also showed that non-adherent fractionated spleen cells from lymphoma-grafted mice produced IL-1 and IL-2. IL-1 was released by asialo-GM1-positive cells and IL-2 by Thy-1-positive cells. Adherent cells released only IL-1. In contrast, total cells released smaller amounts of IL-1 and IL-2, suggesting a reciprocal inhibition between subpopulations of non-adherent and adherent cells. A high level of TNF production by adherent cells was observed only 4 days after the graft. These results indicate that graft of lymphoma cells entails important modifications of spleen cell populations releasing different types of cytokines implicated in NK activation.

Animals↗

Evidence of recombinant ecotropic provirus integration in thymic lymphomas induced by direct or indirect radiation effects.

Several investigators described the occurrence of ecotropic recombinant proviruses in the DNA of in-vivo or in-vitro propagated radio-induced lymphomas, but such proviruses were never detected in primary tumors. To assess their biological significance in the tumorigenic process, we reinvestigated the presence of new proviruses chiefly in primary radio-induced tumors and in models of radioleukemogenesis which could give additional support for their role. Such models included thymic lymphomas originating after (i) graft of non-irradiated thymuses in thymectomized irradiated mice and (ii) the injection of a B-ecotropic retrovirus (T1223/B) in association with a subleukemogenic dose of irradiation. We report for the first time that new ecotropic proviral sequences are encountered in a significant number (30%) of primary lymphomas induced directly by irradiation or indirectly in non-irradiated thymuses grafted in irradiated hosts. The existence of a 3.5-kbp Kpn1 restriction fragment with ecotropic sequences in the digested DNA of these tumor cells indicates that these new sequences belong to an ecotropic provirus recombinant in the gag-pol region. We observed that most of the primary radio-induced tumors in which novel recombinant provirus could be detected, displayed the integration at a single or at a few sites, demonstrating their clonality with respect to viral integration. The same was observed in thymic lymphomas arising after T1223/B virus injection and irradiation and in in-vivo or in-vitro propagated tumors. Altogether, these data bring the first evidence of the integration of ecotropic recombinant proviral genomes in a significant number of primary radiation induced thymic lymphomas and of their possible role in view of their frequent occurrence in grafted thymomas.

Animals↗