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Biomedical subjects

M Pelletier

Publications and source records attributed to M Pelletier.

At least 91 records · Page 5Linked to original sources

Histological and immunopathological studies of delayed hypersensitivity reaction to tuberculin in mice.

At 4 to 6 weeks after intravenous infection with 2 X 10(4) CFU of dispersed Mycobacterium bovis bacilli (BCG), C3H/HeNCrIBR and C57BL/6NCrIBR mice exhibited a strong reaction to purified protein derivatives, as evaluated by the increase in footpad swelling at both 24 and 48 h after local antigenic challenge. However, histological studies of the footpad skin demonstrated a prominent perivascular infiltration with polymorphonuclear cells at 6 and 24 h after purified protein derivative challenge, whereas mononuclear cells represented the majority of infiltrating cells only at 48 h. An immunopathological study of the footpad skin showed granular deposits of immunoglobulins and complement in vascular walls and perivascular tissues at 6 and 24 h. These results demonstrate that the footpad swelling observed 24 h after the antigenic challenge is caused by an Arthus-type reaction, whereas that caused by cell-mediated immunity appears at 48 h. Hence, delayed hypersensitivity must be evaluated at 48 and not 24 h after challenge.

Animals↗

Study of Langerhans cells after allogeneic bone marrow transplantation.

We assessed the number of Langerhans cells (LC) before and after bone marrow transplantation (BMT) in 27 patients in order to study the fate and behavior of these dendritic antigen-presenting cells following allogeneic BMT. LC were identified using monoclonal antibody OKT6 on skin biopsies performed on days - 10, 0, 11, 25, 39, 120, and 365. In a control group composed of 15 healthy adults aged 20-37 yr, the mean number of LC (+/- SEM) was 25.6 +/- 1.17/0.1 sq mm of epidermal surface. Our study shows that pretransplant, the number of LC in patients with aplastic anemia or leukemia was lower than that of controls. The finding of low numbers of LC in patients with untreated aplastic anemia is suggestive of a medullary origin of LC in man. Moreover, during the early posttransplant period, nearly all patients present a severe deficit in LC. This deficit may delay the maturation of their immune system. The number of LC reaches nearly normal levels 4-12 mo after BMT. Finally, we have noted a significant impairment of LC reconstitution in patients with acute graft-versus-host disease (GVHD), providing evidence that this defect may be an important mechanism involved in acute GVHD-related immunodeficiency.

Acute Disease↗

Modifications of the structures of the rat lymph nodes by neonatal thymectomy.

Until recently, the deep cortex of the lymph node was thought to exist as a layer completely underlying the peripheral cortex. It was known, moreover, that through neonatal thymectomy, the lymphocyte population of the deep cortex could be depleted. Through our current research, however, we have demonstrated that the deep cortex actually consists of hemispherical 'units'. Each unit is centered under an opening of an afferent lymphatic and comprises a center and a periphery with different morphological features and functions. In the light of this new knowledge, we felt it appropriate to reexamine the influence of neonatal thymectomy on node histology. Rats were thymectomized 5 h after birth. When they were 8 weeks old, nodes from various anatomical sites were submitted for morphological analysis. The resulting observations were compared to those made with nodes of nude as well as normal rats. It was found that the histological changes induced by neonatal thymectomy were comparable to those resulting from the congenital athymic state, but with marked differences. Differences were also observed in the nodes of thymectomized and semi-thymectomized rats. The discussion deals with these differences and presents new observations.

Animals↗

Acute non-specific inflammation and modification of macrophage and lymphocyte functions.

The acute inflammatory response is a common phenomenon experienced by the physician in a wide variety of clinical situations. One of the major problems facing the investigator in this field of research who wishes to look at the cellular and humoral responses involved, is that in most of the animal models previously used, the inflammatory reaction has been provoked in subcutaneous tissues. Thus, a quantitative assessment of leucocyte emigration and mediator production in the inflamed area is technically difficult without resorting to complicated and artificial methods. Inflammation provoked in the pleural cavity provides a useful tool in the study of these problems since the collection of cells and analysis of humoral factors in exudates is easily accomplished. Among the irritants that may be used, we focused our interest on calcium pyrophosphate (CaPP) crystals, a non-diffusible, non-antigenic and endotoxin-free irritant, because their deposition is implicated in pseudogout and chondrocalcinosis in man (MacCarty, 1973). Calcium pyrophosphate-induced pleurisy is typified by an acute reaction, dominated by polymorphonuclear leucocytes, reaching its maximal intensity at about 5 h and disappearing within 48 h (Willoughby et al., 1975). It was found to be independent of the complement system. Examination of the known mediators of inflammation revealed no significant participation of either histamine or 5-hydroxytryptamine. There was an early rise in PGE2 followed by a greater rise in PGF2 alpha as the reaction diminished (Capasso et al., 1975). More recently, we have demonstrated the presence of a small quantity of thromboxane and a large quantity of prostacyclin during the first 2 hours of this inflammatory process. It was also shown that this type of acute inflammation was accompanied by the very rapid liberation of acute phase proteins both locally, in the exudate, and systemically in the serum (Tissot et al., 1983). Some of these events were also examined during the pleural reaction to other types of irritants (Capasso et al., 1975) and gave similar results (Tissot et al., 1983).

Animals↗

[Stimulation of mitotic activity of bone marrow cells in an acute inflammatory reaction. Implication of serum factors].

A nonspecific acute inflammatory reaction, induced in mice by an intrapleural injection of dextran, is able to increase, in vivo, the mitotic index of bone marrow cells. The transfer of this phenomenon to normal mice can be obtained by the injection of pure or diluted sera from animals developing an acute non-specific inflammation. This activity may also be found in the serum of normal mice but at a much lower level. The stimulatory activity is also observable in vitro when bone marrow cells are incubated with inflammatory serum. This activity is recoverable after ultrafiltration in the fraction less than 10 000 daltons. These results suggest the existence in sera of stimulating factors for hematopoiesis and furthermore that these stimulatory activities are increased during the process of inflammation.

Acute Disease↗

Immunopathology of BCG infection in genetically resistant and susceptible mouse strains.

Natural resistance to Mycobacterium bovis (BCG) is under the control of a single gene, designated Bcg. Resistant (Bcgr) mice prevent multiplication of an i.v. injected inoculum of congruent to 10(4) dispersed BCG cells, whereas progressive multiplication of this pathogen occurs in the first 3 wk of infection in spleens and livers of susceptible (Bcgs) mice. Striking differences in the development of cellular immunity, as measured by granuloma formation in the liver and spleen, delayed-typed hypersensitivity, and a resistance to the challenge with homologous (BCG) and heterologous (Listeria monocytogenes) pathogens, were detected between Bcgr (C3H/HeN and A/J) and Bcgs (C57BL/6J and B10.A) strains. Cellular immune reactions progressively developed in the Bcgs mice, as a response to the increasing bacterial load, whereas greatly inferior levels of acquired immunity were observed in Bcgr strains. These findings support the concept that mice genetically resistant to BCG infection are able to prevent bacterial multiplication without the need for a cellular immune response, whereas genetically susceptible mice will eventually control bacterial multiplication with the acquisition of cellular immunity.

Animals↗

[New technic for detecting anti-double-stranded DNA antibodies. Value in disseminated lupus erythematosus in children].

Two assays for antibodies to double stranded (ds) DNA were compared in children with systemic lupus erythematosus (SLE). An indirect immunofluorescent test using Crithidia luciliae (IF-CL) was more specific but slightly less sensitive than the DNA binding assay (RIA). Detection of antibodies to ds-DNA (anti-ds-DNA) by IF on 3 different trypanosoma (T. brusei, T. equiperdum, and T. musculi) was as specific and as sensitive as IF-CL, but more difficult to read microscopically. No correlation was found between immunoglobulin (Ig) class of circulating anti-ds-DNA and severity of renal disease in SLE. A comparison of serologic and immunohistopathologic (kidney and skin) data in 12 children with SLE showed that immune-complex glomerulonephritis was more frequently encountered when anti-ds-DNA was detected in serum, and that Ig deposits were found only in the skin when anti-ds-DNA could not be detected in serum.

Antibodies, Antinuclear↗

Limitations of the direct immunofluorescence test for antibody-coated bacteria in determining the site of urinary tract infections in children.

The results of the direct immunofluorescence test for antibody-coated bacteria to determine the site of a urinary tract infection do not always correlate with the clinical data. When this test was performed on urine specimens from 282 children with significant bacteriuria, false-negative and false-positive results were observed in 20% (19/94) and 52% (19/188) of the specimens. Contamination of the specimen during collection and the presence of Fc receptors (receptors for the crystallizable fragment of the immunoglobulin molecule) on the surface of some strains of Staphylococcus aureus yielded false-positive results, and stools and vaginal secretions were shown to be potential sources of antibody-coated bacteria. It is suggested that for children this test be run on urine collected by bladder puncture. The use of conjugated anti-IgG antiserum containing only F(ab')2 (the antigen-binding fragments of the IgG molecule) is also recommended to eliminate false-positive results due to the presence of Fc receptors on the bacterial surface.

Adolescent↗

Effects of sera and exudate from carrageenan-treated rats on two models of acute inflammation.

The air bleb has been studied as a cavity suitable for the production of a chronic inflammatory response. The ability of carrageenan and CPPD crystals to produce a chronic response in this cavity has been studied and the nature of the reaction described quantitatively and qualitatively. Carrageenan produced a fluid exudation predominated by mononuclear cells and histologically chronic in nature. However, CPPD failed to produce an inflammatory response apart from the formation of a few foreign body giant cells. Using the model described, experiments were undertaken to examine the ability of exudates and sera taken from animals undergoing either an acute or chronic reaction to modify two models of acute inflammation. Firstly the carrageenan complement dependent pleurisy and secondly the CPPD complement independent pleurisy. Volume of chronic and acute total cell numbers were reduced by chronic and acute exudates and sera on the carrageenan pleural model. No significant effect was on the CPPD pleural model.

Animals↗

Primary nephrosis in childhood associated with focal glomerular sclerosis: is long-term prognosis that severe?

In our study, 32 nephrotic children with focal glomerular sclerosis were observed for an average period of 8 years (ranging 1-19 years of age). Of the 32, 25 children showed histological lesions of focal segmental sclerosis (FSG) and 7 of focal global glomerulosclerosis (FGG). All patients were reevaluated in 1979, creating the most recent status as follows: for children with FSG, 6 (24%) are in remission, 10 (40%) have a relatively normal renal function but exhibit either a persisting proteinuria (PP) or a recurrent nephrotic syndrome (NS), 1 (4%) is in chronic renal failure, 5 (20%) required dialysis and transplantation, and 3 (12%) died from non-renal causes. For children with FGG, 4 (57%) are in remission, 2 (29%) have a good renal function but display either PP or NS, and 1 patient (14%) is in chronic renal failure. The long-term observation of our study shows a more favorable prognosis than the one reported in researched literature. We believe that such results reflect a difference in the type of population encountered in our institution. Our population of patients represents less a highly referred population than the one of the centers who reported similar long-term studies, and we believe therefore that our study may represent a wider spectrum of the natural history of the disease. Moreover, the group of patients with PP or NS does not show a progressive decrease of glomerular filtration rate with time, which suggests that the disease may progress in a stepladder fashion.

Adolescent↗

Kidney transplantation in uremic children with cystinosis.

10 children underwent cadaveric renal transplantation between the ages of 8.0 and 12.5 years for uremia secondary to infantile cystinosis. 6 children are doing well 6-62 months after-transplantation. 3 of the 4 other recipients required a second graft and eventually died of uremia or fulminant viral encephalitis, the other lost her first graft due to accelerated acute rejection and is now on maintenance hemodialysis. No further systemic complications of cystinosis have been observed in the patients with functioning grafts. Our experience confirms that kidney transplantation is the treatment of choice for uremic children with infantile cystinosis.

Cadaver↗

Induction of macrophage DNA synthesis in vitro, by non-immunological inflammatory sera: effect of irradiation and thymus or bone marrow cell reconstitution.

The mitogenic activity on macrophages of acute inflammatory serum is increased when this serum is obtained from irradiated rats. Transfer to irradiated rats of normal syngeneic thymic or bone marrow cells enhances the mitogenic activity of inflammatory serum. The enhancement of mitogenic activity is more pronounced after transfer of cells harvested from rats with an acute inflammatory reaction. It is postulated that the mitogenic activity of inflammatory serum could be related to both thymic and bone marrow cells and that this cellular activity is enhanced when inflammation is present.

Animals↗