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Biomedical subjects

L Mandel

Publications and source records attributed to L Mandel.

At least 127 records · Page 7Linked to original sources

The use of gnotobiological models for the studies of immune mechanisms.

Germfree (GF) animals are widely used for discrimination of natural mechanisms (genetically determined) from adaptive mechanisms of immunity induced by external antigens. GF rats fed at least for first 5 days after birth with artificial diet LNa, deficient in unsaturated fatty acids, were in contrast to those fed with K 50 diet deeply suppressed in humoral and cellular immune reactivities during their life. GF piglets, deprived from maternal colostrum (CF) as a source of passively transferred maternal antibody, immunized with preformed Ag/Ab complexes (HSA anti HSA) responded according to the composition of complexes (Ab excess, equivalence, Ag excess) by low or high dose tolerance or by secondary response. Similar pictures of response were obtained in groups of presensitized GF-CF piglets by immunization with different doses of antigen. It is concluded that 3 different types of response are the result of Ag/Ab complexes acting or formed on the lymphocyte membrane and exerting stimulatory or down-regulatory signals.

Animal Nutritional Physiological Phenomena↗

The minipig as a model in gnotobiology.

Due to its close physiological and morphological resemblance to man, the pig occupies an important position in biomedical research. The minipig lends itself particularly well to germfree research. It is easy to deliver, maintain, and utilize in isolators. The colostrum-free, newborn germfree piglet lacking passively obtained antibodies is of an exclusive use if distinguishing the factors of natural and adaptive immunity is needed. It fits also well in studies investigating the earliest mechanisms of antibody synthesis. Under germfree conditions, the pig has been proved an excellent model for testing the action of ionizing radiation as well as of selected bacterial strains when monoassociated. Recently, conventional pigs have been used also for studies in total or selective decontamination of the intestinal tract by antibiotics and strict isolation.

Animals↗

Germ-free newborn baby.

Long term experience with germ-free animal experiments and technology encouraged us to apply the know-how in the field of the care of human neonates with presumed immunodeficiency. The program was carried out at the Faculty of Pediatrics of Charles University in Prague. The sterile caesarean section was performed within the plastic surgical isolator overlying the pregnant mother. A new type of this isolator adapted for the use in human medicine was designed and constructed. For the care of the neonate another special isolator was used. The whole isolator system included two rigid supply isolators, too. The newborn was sterile up to the age of 1 month. During this time, the newborns immunological capacity was investigated and found to be almost normal. Afterwards, the infant was gradually colonized with selected strains of bacteria and thus prepared for conventionalization.

Cesarean Section↗

Immunologic markers and fine structure of alveolar cells in germfree pigs.

The objective of this study was to evaluate neonatal development of alveolar cells without any antigenic stimulation. The cells obtained by bronchoalveolar lavage from newborn and germfree Minnesota miniature piglets were characterized ultrastructurally and using different markers of pig lymphocytes and macrophages. Alveolar cells from newborn animals did not express any immunologic markers or phagocytic activity. Cells of the pulmonary immune system appeared in the airways at the twelfth hour, phagocytosing macrophages within the first day of postnatal life. Fc receptors were expressed sooner than complement receptors. Almost all lymphocytes were null cells. Macrophages and lymphocytes immigrated into alveolar spaces independently of external antigenic stimuli.

Animals↗

Lysosomal enzyme activities in polymorphonuclear leukocytes, macrophages, serum, and spleen of conventional, germ-free, and antigen-free Minnesota miniature swine.

The activities of lysozyme, myeloperoxidase, and elastase were lower in PMNs and AMs from GF and AF Minnesota miniature piglets than in the leukocytes from their CONV counterparts. In the spleen and serum of gnotobiotic piglets only the levels of lysozyme were slightly reduced. Substantially depressed activities of these LEs were found also in PMNs from precolostral piglets in comparison with PMNs from their CONV mother. The bisassociation of GF piglets with Enterococcus liquefaciens and Escherichia coli caused an increase of LE activities in their AMs, spleens, and sera. Fewer LEs were released after phygocytic stimulation with zymosan from PMNs of GF, AF, and precolostral piglets than from PMNs of CONV animals of the same age. These data suggest that the antigenic-microbial stimulation is important for the development of normal lysosomal enzyme activities in PMNs and AMs from gnotobiotic animals.

Animals↗

Selective decontamination, induced colonization resistance and connected immunological changes in piglets.

14-d-old conventional piglets were picked from normal piggery, washed with disinfectants, placed into isolators suitable for germfree work, fed a sterile diet and treated with peroral antibiotics (nalidixic acid, kanamycin, and nystatin). Beginning with day 5 or 7, Enterobacteriaceae were not found in feces. The absence of these bacteria was proved by inoculation of germfree newborn piglets with caecal content. In selectively decontaminated piglets, the white blood cell count in blood had fallen to 6 X 10(9)/L; this decrease was due to an extremely low number of granulocytes (to 0.8 X 10(9)/L). On day 35, IgG-positive cells almost disappeared from the spleen, whereas IgA cells were found in an unusually great amount. Corresponding changes in serum levels were established. The colonization resistance effect in Enterobacteriaceae-deprived piglets was confirmed; settling of introduced various E. coli strains did not occur or was delayed.

Animals↗

Protective activity of Streptococcus faecalis against pathogenic action of Escherichia coli O55 in gnotobiotic pigs.

Peroral administration of Streptococcus faecalis suppresses the lethal effect of simultaneous or subsequent infection with pathogenic Escherichia coli O55 in gnotobiotic colostrum-free piglets. The presence of S. faecalis in the intestine and mesenteric lymph nodes in artificially diassociated colostrum-free piglets influences neither multiplication of E. coli in the intestine nor its penetration into the organism.

Animals↗

Ontogeny of J chain expression in pig lymphocytes.

The ontogeny of lymphocytes expressing J chain in the cytoplasm (J+) was studied in pig foetuses by the immunofluorescent technique. Peripheral blood lymphocytes were the first J+ cells in prenatal life. The spleen and lymph nodes contained J+ cells in the last days of gestation. J+ cells were found in the lamina propria of the gut and some glands of conventional but not of germ-free piglets. J chain was not detected on or in cell membranes at any developmental stage.

Animals↗

Interaction of xenogeneic antiglomerular antibodies with foetal pig tissues.

Rabbit anti-swine-glomerular-immunoglobulin (AG Ig) was administered in utero to 14 pig foetuses 40-103 d post-conception. In nine foetuses AG Ig was injected into the umbilical vein and 60 min later kidneys and other organs were collected. In five others, AG Ig was injected via the intact uterine wall, and the tissues were examined after further 11 or 35 d of uninterrupted pregnancy. No signs of glomerular inflammation were found by light microscopy. In electron microscopy, especially in younger foetuses, focal endothelial defects and subendothelial granular "deposits" were seen in deep glomeruli, but they appeared also in control foetuses of corresponding age. Immunofluorescence microscopy showed a strong diffuse linear positivity of the swine-anti-rabbit-Ig conjugate in the capillary loops of deep juxtamedullary glomeruli irrespective of foetal age and dose of antigen injected. Immature glomeruli and S-bodies yielded a poor to negative staining. Proof of swine Ig was negative in all kidneys as well as the test for rabbit and swine Ig in various other organs. Traces of rabbit Ig were only detected in disseminated platelet aggregates of myocardium in the early post-injection period. Ultrastructural enzyme-antibody assay visualized AG Ig throughout all three layers of glomerular capillary basement membrane, and in the early period signs of transendothelial passage and escape of unbound rabbit Ig molecules were evident. The mesangial matrix, cell membranes, and extraglomerular basement membranes remained all negative. As follows, xenogeneic antiglomerular antibodies specifically react with target structures even at the end of the first third of intrauterine life, afflicted being only the deep mature polyanion-coated glomeruli. The foetal immune system is incapable of an adequate autologous antibody response, and we have failed to find even an early glomerular lesion comparable with the postnatal anti-basement-membrane glomerulonephritis.

Animals↗