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Biomedical subjects

M Pelletier

Publications and source records attributed to M Pelletier.

At least 73 records · Page 4Linked to original sources

Demonstration of OKT6 antigen on human thymic dendritic cells in culture.

In situ, two types of dendritic cells (DCs) have been characterized in more detail: the interdigitating DCs of peripheral lymphoid tissues and the epidermal Langerhans cells. In order to characterize human thymic DCs, normal human thymus specimens were obtained from children undergoing cardiovascular surgery. In culture, DCs could be easily differentiated from macrophages and epithelial cells by their long fine processes, irregular nucleus, and dark, membrane-bound granules. By immunoelectron microscopy, using the protein A-gold and the avidin-biotinperoxidase complex techniques, cultured DCs were strongly labeled with anti-Ia and anti-OKT6 monoclonal antibodies. These results demonstrate that the phenotype of thymic DCs is similar to that of epidermal Langerhans cells and suggest that they may belong to the same cellular lineage.

Antibodies, Monoclonal↗

Morphological anomalies in the lymph nodes of 13-month-old thymus-grafted nude mice.

The purpose of the present work was to investigate whether the grafting of a thymus to 7-day-old BALB/cByJ nude mice prevents the occurrence of the nodal anomalies recently observed in non-grafted nude mice. We found that the anomalies were still present, but attenuated, in the grafted mice. Furthermore, we observed differences between anomalies occurring in grafted and in non-grafted nude mice. The differences appear to be interrelated and to result from changes in the pattern of lymphocyte migration in the nodes of grafted nude mice, due to a lesser deficiency of the immune system.

Animals↗

The modification of the oxidative metabolism of cells derived both locally and at distance from the site of an acute inflammatory reaction.

During an acute nonspecific inflammatory reaction initiated in the pleural cavity by a nondiffusible stimulus (calcium pyrophosphate crystals), the oxidative metabolism, as measured by chemiluminescence and superoxide release, of cells harvested from both the inflammatory site and at points distant from it was studied. The oxidative metabolism of peritoneal macrophages, obtained from rats undergoing an inflammatory reaction (pleurisy), demonstrated a transient decrease in activity compared with the resident population when using both zymosan and phorbol myristate acetate as stimulants. This metabolic unresponsiveness induced by inflammation may be related to the concomitant changes in the levels of prostacyclin in the peritoneal cavity. It should be emphasized that the peritoneal cellular composition or number did not change during these events. On the other hand alveolar macrophages from inflamed animals showed no significant changes in their superoxide production or chemiluminescence compared to controls. The precise reason for these inflammation-induced changes is unknown; however the acute nonspecific inflammatory reaction was able to modulate the oxidative metabolism of cells not only at the site of inflammation, but at points distant from it.

Acute Disease↗

Persistence of host Langerhans cells following allogeneic bone marrow transplantation: possible relationship with acute graft-versus-host disease.

Langerhans cells (LC) are bone marrow-derived dendritic antigen-presenting cells found in the epidermis. In an effort to determine the origin (host versus donor) of LC at different intervals following bone marrow transplantation, we performed skin biopsies in 16 recipients of sex-mismatched marrow. LC were identified using monoclonal antibody OKT6 in an indirect immunoperoxidase assay and their donor or host origin determined according to the presence or absence of Y body. The presence of Y-positive (donor) LC could be demonstrated in all (6/6) skin biopsies of female recipients of male marrow tested between days 39 and 730 post-transplant. Persistence of host LC in male recipients of female marrow was documented in all (6/6) recipients studied on day 39 and in two out of seven patients tested on day 120 post-transplant. From day 365 onward, no residual host LC could be detected, suggesting that by this time all epidermal LC are donor-derived. Our study demonstrates that host LC usually persist for 39 and up to 120 d following bone marrow transplantation. The relevance of this observation to the possible role of LC and other host dendritic antigen-presenting cells in the graft-versus-host reaction is discussed.

Acute Disease↗

Genetic resistance to murine cryptococcosis: increased susceptibility in the CBA/N XID mutant strain of mice.

In a survey of 301 normocomplementemic inbred mice (belonging to nine different strains: BALB/cN nu/nu and nu/+, CBA/N, C57BL/KsJ, C57BR/cdJ, CBA/CaJ, BRVR, DW/+, and C57BL/6J) for natural resistance to Cryptococcus neoformans, cumulative survival values were found to range from 12 to 22 days. When the average organ weights of infected animals were compared with reference values obtained in uninfected mice of the same age and genetic lineage, the following changes were documented. In the CBA/N strain, the mean spleen and brain weights increased 313 and 13.5%, respectively, whereas the mean liver weight remained unchanged. In the CBA/Ca strain, cerebral cryptococcosis was the dominant clinical feature, and a 54% increase in mean brain weight was recorded at the time of death. The averaged liver weight was drastically lower, whereas spleen weight values evinced a biphasic pattern of transient splenomegaly followed by involution. At the median time of death, CBA/N mice had significantly more cryptococci in the liver and spleen than corresponding CBA/Ca mice. In the (CBA/N X CBA/Ca)F1 mice, susceptibility to C. neoformans segregated according to the sex-linked inheritance of the X-linked immunodeficiency (xid) gene. It is concluded that (i) susceptibility to cryptococcosis is under multigenic control, (ii) the xid locus on the X chromosome influences susceptibility to cryptococcosis, and (iii) xid mice behave differently than CBA/Ca mice in their organ response during the course of the infection.

Animals↗

Genetic resistance to murine cryptococcosis: the beige mutation (Chédiak-Higashi syndrome) in mice.

The influence of the bgJ and bg2J mutations on the susceptibility of mice to experimental cryptococcosis was studied in inbred mice of the C57BL/6J and C3H/HeJ strains. Although infected animals with the bg/bg genotype had a significantly shorter lifespan than bg/+ or +/+ animals, C3H/He beige-2J mice were less susceptible than C57BL/6 beige-J mice when compared with nonbeige mice of similar background. On days 18 and 19 after infection, quantitation of cryptococci in the brain, liver, and spleen revealed that the overall burden of organisms in infected C57BL/6 beige-J mice was in excess of one log unit above that found in the brain, liver, and spleen of infected C57BL/6 +/+ mice. At that time, C57BL/6 beige-J mice showed a 53% increase in mean brain weight, a 67.8% decrease in mean liver weight, and a 58.6% decrease in mean spleen weight, when compared with uninfected animals of the same age and genetical lineage. The corresponding figures for C57BL/6 +/+ mice were a 32% increase in mean brain weight, a 41.4% decrease in mean liver weight, and a 23.4% decrease in mean spleen weight. From these data, it is concluded that the beige mutation in mice is associated with increased susceptibility to cryptococcosis, the accrued susceptibility of the beige mutant is related to more rapid changes in the weight profile of the target organs as well as to a higher rate of growth or decreased clearance of Cryptococcus neoformans or both, and other autosomal genes are likely to be involved in the genetic control of susceptibility to murine cryptococcosis.

Animals↗

Evolution of cell types and T-cell subsets in the spleens of Mycobacterium bovis BCG-resistant and M. bovis BCG-susceptible strains of mice after infection with M. bovis BCG.

In mice, the early host response to intravenous infection with small doses of dispersed Mycobacterium bovis BCG is controlled by the Bcg gene. After infection with a low dose of M. bovis BCG, Lyt-1+ cells were generated in the spleens of BCG-susceptible mice (Bcgs) in parallel with an increase in the proportion of phagocytic cells. Very few changes occurred in the splenic cell types of BCG-resistant mice (Bcgr).

Animals↗

beta-NADPHase- and TMPase-positive "snake-like tubules" in the exocrine pancreas: cytochemical and immunocytochemical studies.

Using five different protocols, two enzymes, nicotinamide adenine dinucleotide phosphate phosphohydrolase (beta-NADPHase) and sodium trimetaphosphatase (TMPase), were localized in the acinar cell of rat pancreas by ultrastructural cytochemistry. The beta-NADPHase cytochemical localization was realized at pH 4.8 and pH 3.9. At pH 4.8, the beta-NADPHase activity was found in the Golgi intermediate saccules, lysosomes, gland lumen, and tubular structures, described as snake-like tubules (Beaudoin AR, Grondin G, Lord A: Eur J Cell Biol 33:275, 1984; Beaudoin AR, Grondin G, Lord A, Pelletier M: In Proc 42nd Ann Meeting Electron Microscopy Soc Am. San Francisco Press, CA, 1984). There was no detectable beta-NADPHase activity at pH 3.9. The TMPase cytochemistry was done at pH 3.9 according to Oliver (J Histochem Cytochem 28:78, 1980) and at pH 3.9 and 4.8 with the medium described by Berg (J Histochem Cytochem 8:92, 1960). TMPase localization varied according to the protocols. It was found in tubular structures described as "basal lysosomes," lysosomes, and zymogen granules, whereas Golgi saccules were generally negative. Our observations showed that the structures identified as "basal elongated lysosomes" and revealed by TMPase (Oliver C: J Histochem Cytochem 28:78, 1980; J Histochem Cytochem 31:1209, 1983) were morphologically similar to snake-like tubules (SLT) revealed by beta-NADPHase. Relationships between SLT and mitochondria as well as lysosomes and plasma membranes were observed. Using amylase-specific antibodies, it was also shown, by the protein A-gold immunocytochemical technique, that SLT do not contain amylase and, in fasting conditions, would not be involved in the transport of secretory proteins.

Acid Anhydride Hydrolases↗

Cellular immune response to Mycobacterium bovis (BCG) in genetically-susceptible and resistant congenic mouse strains.

Congenic Bcgr (C.D2, resistant) and Bcgs (BALB/c, susceptible) mice were infected intravenously with Mycobacterium bovis (BCG, strain Montreal) in order to establish the relationship between different indicators of the cell-mediated immune response and the bacterial load attained in the host. There was a correlation between the bacterial burden and the splenomegaly response, granuloma formation in the liver and cross-protection against an heterologous pathogen (Listeria monocytogenes) in Bcgr and Bcgs mice. No relationship was found between bacterial load or granuloma formation and the development of specific acquired protection against an homologous organism (BCG or M. tuberculosis, H37Rv) as assessed by the level of resistance attained in BCG-primed mice challenged with virulent H37Rv or by the adoptive immunity conferred by BCG-primed spleen cells transferred to naïve irradiated recipients challenged with BCG.

Animals↗

[Allergic rhinitis].

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Diagnosis, Differential↗

Development of the lymph nodes in the very young, and their evolution in the mature, nude rat.

We recently revised the concepts on the morphology of the lymph nodes of the young adult athymic nude rat. The present work studied the postnatal development of its nodal structures and their evolution with aging. The structural development of the deep cortex "units" was found to progress as usual. However, while the concentration of lymphocytes appeared to develop normally in the periphery of a unit, the center of the unit remained lymphocyte-depleted. Further, the peripheral cortex failed to develop over the middle part of a unit center. With aging, the peripheral cortex over the remainder of a unit center could atrophy and disappear completely. The present findings did not yield information as to whether thymic elements are necessary to trigger the development of a unit, but they revealed that its further development is determined by stimuli. It was concluded that, in the absence of T-cells, stimuli for cellular immune responses provoke the proliferation of the reticular or interdigitating cells of a unit center. On the other hand, an increase of these stimuli was concluded to cause the peripheral cortex to fail to develop over part of a unit center and, later, to atrophy over the remainder of the unit center. The mechanisms of the phenomena are discussed.

Aging↗

Modification of thymo-dependent and thymo-independent antibody responses during non-specific acute inflammation.

An acute non-immunological inflammatory reaction, induced in mice by injecting intrapleurally a non-bacterial, non-antigenic and endotoxin-free irritant (40,000 molecular weight dextran or monoclinic dihydrated calcium pyrophosphate microcrystals), provoked an increase of antibody responses to thymus-dependent SRBC or thymus-independent TNP-LPS or DNP-Ficoll when the phlogistic stimulus was applied before immunisation. The increase in the number of IgM plaque-forming cells per spleen was obtained for different time intervals between the induction of the inflammatory stimulus and the antigen administration according to the type of irritant and the antigen used. However, no stimulation could be observed when this time interval was greater than three days. No stimulation of the antibody response to SRBC was observed when the irritant was applied one to three days after the antigen. The (stimulatory) effect could not be entirely related to a polyclonal activation as an augmentation in the production of antibody against non-cross-reactive antigen could only be seen four days after the onset of the inflammatory process, when the specific antibody response was not maximal. These observations indicate that an acute non-immunological inflammatory reaction lasting for 48 h can affect the immune reactivity of the host, even after the inflammatory process has disappeared.

Acute Disease↗

Direct and indirect in vivo stimulation of LAF-like production induced by acute nonspecific inflammatory processes.

Peritoneal macrophages harvested from animals undergoing an acute non-immunological inflammatory reaction induced by an injection of calcium pyrophosphate ( CaPP ) or dextran into the pleural cavity showed an enhanced level of production of a lymphocyte activating factor (LAF) like material. On the other hand, macrophages harvested from the site of inflammation did not show enhanced production of this activity when compared to macrophages derived from normal controls. This enhanced activity was observed for up to two/three days after initiation of the inflammatory reaction and was obtained in both the presence and absence of lipopolysaccharide (LPS) during in vitro cultivation. Thus these results demonstrate that the acute inflammatory reaction, initiated by a non-antigenic stimulus ( CaPP ), is able to stimulate macrophages remote from the inflammatory site to produce a factor which behaves like LAF in a standard LAF assay.

Animals↗