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F Pflumio

Publications and source records attributed to F Pflumio.

47 records · Page 3Linked to original sources

Transplantation of normal and leukemic human bone marrow into immune-deficient mice: development of animal models for human hematopoiesis.

The successful engraftment of human hematopoietic cells into immune-deficient mice offers a novel approach to characterize the developmental program of human hematopoiesis. While it is not yet possible to achieve high-level engraftment of all human lineages, several methods have been developed to successfully engraft human lymphoid cells and reconstitute partial immune function. In addition to mature cell types, there is evidence that progenitors and perhaps stem cells can engraft the murine bone marrow. Recent work suggests that provision of exogenous human cytokines significantly increases the level of human cell engraftment and stimulates the development of multiple lineages. Progress has also been made to establish animal models of human hematopoietic diseases such as leukemia, autoimmunity, and infectious diseases.

Animals↗

Immunoglobulin isotypes of C57BL/6 nu/nu, lpr/lpr mice. Lack of direct intrinsic effect of the lpr gene on B cell hyperactivity.

The absolute concentrations of mouse immunoglobulin (Ig) heavy chain isotypes were determined by specific ELISAs in the serum of C57BL/6 (B6) mice doubly homozygous at the nude (nu) and the lymphoproliferation (lpr) locus (B6 nu, lpr mice), and compared with normal B6 nu mice. The distribution and the absolute concentrations of all Ig isotypes were found to be very similar in B6 nu, lpr and B6 nu mice, for both sexes and with similar increases in titers with ageing. Thus, the major part of the severe autoimmunity and hyperglobulinemia characteristic of the lpr syndrome of euthymic B6 lpr mice, including their elevated titers of thymus-independent IgM and IgG3 isotypes, is abrogated by the nude mutation, an effect of which is the lack of thymus differentiation. Though a postulated intrinsic activity of the lpr gene directly on B cell hyperactivity cannot be discarded, its expression would then require the presence of either the thymus or of T cells or of other cells or factors whose expression is also abrogated by the homozygosity at the nude locus.

Aging↗

Mouse models for human hematopoiesis.

The successful engraftment of human hematopoietic cells into immune-deficient mice offers a novel approach to characterize the developmental program of human hematopoiesis. While it is not yet possible to achieve high level engraftment of all human lineages, several methods have been developed to successfully engraft human lymphoid cells and reconstitute partial immune function. In addition to mature cell types, there is evidence that progenitors and perhaps stem cells can engraft the murine bone marrow. Recent work suggests that provision of exogenous human cytokines significantly increases the level of human cell engraftment and stimulates the development of multiple lineages. Progress has been made to establish animal models of human hematopoietic disease such as leukemia, autoimmunity, and infectious diseases. One major challenge for the future will be reconstitution of mice with the entire human hematopoietic system.

Animals↗

Impaired antibody response of C57BL/6 beige mutant mice to a thymus-independent type 2 antigen.

The murine equivalent of the human Chediak-Higashi Syndrome is the beige (bg) mutant in the C57BL/6 (B6) background. Besides the well-known lack of natural killer (NK) activity in bg-homozygous mice, functional abnormalities of T cells, macrophages and various granulocytes have been reported. With the exception of one study indicating a decreased in vitro response to lipopolysaccharide, there is no report concerning the B cell compartment of the beige mutant. The in vivo anti-trinitrophenyl antibody response to a TI-2 antigen (TNP-Ficoll) was found here to be significantly lower in B6 beige than in B6 wild mice, although both strains responded similarly to an analogous TD antigen (TNP-ovalbumin). Since the marginal zone macrophages of the spleen were previously shown to be essential for the initiation of antibody responses to TI-2 antigens, they might be another target of the beige mutation.

Animals↗

Adoptive transfer of viable motheaten (mev) humoral autoimmunity: IgM to IgG switch of the hyperglobulinaemia in nude, beige recipient mice.

Homozygous C57BL/6 nude, beige mice (B6 nu,bg) were used as recipients for the transfer of lymphoid cells from autoimmune homozygous B6 'viable motheaten' mice (B6 mev) and from either normal B6 mice (B6 wild) or B6 bg mice as controls. Surprisingly, the mev cell grafts prolonged survival of these short-living doubly immunodeficient recipients. Although the [mev----nu,bg] chimeras did not develop the mev external necrosis phenotype, they showed a hyperglobulinaemia and a significant increase of their anti-single-stranded DNA (ssDNA) antibody titres, compared to control chimeras ([bg----nu,bg] and [wild----nu,bg]). However, this hyperglobulinaemia was quite different from the mev-type hyperglobulinaemia, with poor contribution of the IgM isotype. Moreover, the anti-ssDNA antibodies were more distributed among the various Ig classes than the anti-ssDNA antibodies of the mev homozygous mice. Though the adoptive transfer of some mev-type humoral autoimmunity symptoms were achieved in this chimera model, the recipient mice did not suffer from the several other features of the mev syndrom, such as the severe pathology and the extremely high IgM serological levels.

Animals↗

Adoptive transfer of viable motheaten humoral autoimmunity in cyclophosphamide-immunodepressed beige recipient mice.

Cyclophosphamide-pretreated homozygous C57BL/6 beige mice (B6 bg) were used as recipients for the transfer of lymphoid cells either of short-living autoimmune homozygous B6 'viable motheaten' mice (B6 mev) or of normal B6 mice (B6+) or B6 bg mice as controls. The grafts had no incidence on the survival of the recipients, whatever protocol used. The [mev----bg] chimeras did not develop the mev external phenotype, but there was a transfer of humoral autoimmunity. Compared to control Compared to control chimeras ([bg----bg] and [+----bg]), recipients of mev cells always showed an increase in anti-single-stranded DNA (ssDNA) antibody titres, reaching 2/3 of the mev ones 40 weeks after the cell transfers. Moreover, the anti-ssDNA were mainly of IgM class, correlating with the higher total IgM level found in [mev----bg] chimeras, thus reflecting the serological phenotype of the mev homozygous mice. Though the adoptive transfer of some mev-type humoral autoimmunity symptoms was clearly achieved in this chimera model, the recipient mice did not suffer from the several other features of the mev syndrome, such as the hyperglobulinemia and the severe pathology. This indicates that microenvironmental influences act in concert with B cells to produce pathology in mev mice.

Animals↗

The C57BL/6 nude, beige mouse: a model of combined T cell and NK effector cell immunodeficiency.

This article describes the construction and establishment of a double congenic nude, beige C57BL/6 (B6 nu, bg) mouse strain. The mice do not show higher fragility than C57BL/6 nude mice and the double congenic strain can be maintained under conventional mouse housing conditions. Although the B6 nu, bg display a very low natural killer activity which cannot be enhanced by an interferon inducer (poly(I-C], they lack responsiveness to a T cell mitogen (concanavalin A); and they also show extremely low responsiveness to a B cell mitogen (0128: B12 Escherichia coli lipopolysaccharide) probably as a result of combined effects of the beige and nude genes in the C57BL/6 genetic context.

Animals↗

Lymphoid cell transfers between adult C57BL/6 mice differing at the lpr and/or nu locus. Humoral immunity phenotype of the chimeras.

Congenic C57BL/6 mice (B6) homozygous only at the nu (nude, athymic) locus (B6 nu) or also at the lpr (lympho-proliferation) locus (B6 nu, lpr) were used as recipients for the transfer of spleen and/or lymph node cells from either normal B6 mice (B6+) or lpr-homozygous B6 mice (B6 lpr). Highly increased survival was obtained for [B6 lpr----B6 nu, lpr] chimeras, but not for [B6+----B6 nu, lpr] and [B6 nu----B6 nu, lpr] chimeras. All long-term survivors that were killed showed an increased responsiveness to the T-cell mitogen concanavalin A (Con A) but no change of responsiveness to the B-cell mitogen lipopolysaccharide (LPS). Some enlargement of spleen and lymph nodes was observed only in some specific [B6----B6 nu, lpr] chimeras (female recipients of spleen cells). Within a few weeks after cell grafting, all but [B6 nu----B6 nu, lpr] chimeras developed highly increased levels of serum immunoglobulins, as well as a higher occurrence of anti-single-stranded (ss) DNA containing sera. These chimeras had been constructed in order to dissect the components of the lpr phenotype etiopathology (primordial involvement of B and/or T lineage cells, lymphoid and/or environmental influences). Though the evolution of serological parameters showed some chimera type-specific features, it seems difficult to reconstitute the entire expression of the lpr phenotype.

Animals↗

Radiation therapy of spontaneous autoimmunity: a review of mouse models.

The classical types of generalized autoimmune disease in man are systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Several murine strains which develop SLE and sometimes RA-like diseases are now available. They should help in the understanding of the etiopathology of SLE and RA. Basically two main therapeutic strategies which use solely irradiation have been tried; one being sublethal whole-body irradiation (WBI) and the other fractionated total lymphoid irradiation (TLI). Other protocols which combine lethal WBI and stem cell transplantation have often been attempted. It was regularly found that the bone marrow transplant (BMT) dictates the immune status of the recipient. This paper reviews the data published about NZB, NZB/W, BXSB and MRL mice in this context.

Animals↗

[A case of pheochromocytoma with cardiac localization. Review of the literature].

In a 26-year old man who died post-operatively, post-mortem examination revealed the presence of a phaeochromocytoma located in the atrio-ventricular sulcus and involving the trunk and bifurcation branches of the left coronary artery. Pre-operative investigations, including whole-body computerized tomography, and exploratory laparotomy had failed to detect the tumour. In contrast with the case reported here, the 4 other cases previously published concerned intrapericardial phaeochromocytomas in contact with the posterior wall of the left atrium.

Adult↗