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Biomedical subjects

Z Nevo

Publications and source records attributed to Z Nevo.

71 records · Page 4Linked to original sources

Fetal bone grafts do not elicit allograft rejection because of protecting anti-Ia alloantibodies. Implications to the immune survival of fetuses in allogeneic mothers.

In a previous study we showed that allografts of BN fetal bone, unlike allografts of adult bone, are not rejected by allogeneic recipients of the Lewis strain in spite of the existence of major histocompatibility complex (MHC) incompatibility between donors and hosts. In the present study, we analyzed the relationships existing between the host and fetal tissue that determine graft survival. We found that (1) the fetal BN graft, unlike adult grafts, induces in Lewis recipients a vigorous humoral response consisting mainly in the production of IgG antibody that seems to be directed against antigens of Ia-like specificities. (2) The BN rats are genetically defective in their capacity to respond to determinants and thus are not capable of producing anti-Ia antibodies; in accordance, Lewis fetal bone grafts are rejected by the BN recipients. (3) Chondrocytes isolated from fetal mouse bones do express Ia antigenic determinants. We suggest that the survival of an allogeneic fetal graft in an immunologically intact recipient depends on an active and selective immune response directed against the Ia components associated with the MHC on the embryonic and fetal cells. On the basis of these notions, we propose that the capacity of Ia determinants expressed on cells of the embryo, to elicit anti-Ia and IgG alloantibodies in the pregnant mother, determines the capacity of the embryo to escape rejection by the histoincompatible mother.

Animals↗

Hyaluronidase release from guinea pig spermatozoa as affected by reproductive tract secretions and metabolic inhibitors.

Cauda epididymal sperm of mature guinea pigs were incubated (37 degrees, 5% CO2 in air). 10% of the total enzyme activity was released into the medium in 4 hr, 30% in 24 hr. Addition of lysolecithin resulted in rapid release of hyaluronidase. Vitamin C (0.54 mM), sodium fluoride (0.02 M), and cholesterol increased the rate of release whereas citrate (20 mM) diminished it. No effect upon hyaluronidase release was noted upon addition of KCN (10(-2)M), progesterone (250 microgram/ml), testosterone (500 microgram/ml), spermine (1.15 mg/ml), inositol (5.6 mM), or chloroquine phosphate (0.54 mM).

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Stimulation of chondromucoprotein synthesis in chondrocytes by extracellular chondromucoprotein.

Chondrocytes in suspension culture preserve their differentiated state, as expressed by a high rate of chondromucoprotein synthesis. Purified chondromuco-protein added to a suspension of cultured embryonic epiphyseal cartilage cells stimulates the rate of synthesis of chondromucoprotein at concentrations up to 2 mg/ml. The stimulation involved synthesis of the entire molecule since incorporation of labeled serine (into core protein), glucosamine, acetate, or sulfate was increased. Neither the amount of synthesis of total protein nor that of collagen was increased. No elevation of xylosyltransferase and N-acetylgalactosaminyltransferase activities was observed. The stimulation was produced by several other polyanionic substances. No evidence was found of the entry of chondromucoprotein into chondrocytes under the conditions of the experiments. Mild trypsinization lowered the response to added chondromucoprotein and decreased the endogenous rate of chondromucoprotein synthesis. Incubation of cells after trypsinization results in restoration of the rates of chondromucoprotein synthesis. The endogenous, as well as the stimulated, rate of chondromucoprotein synthesis varied with the density of chondrocytes in culture. It is suggested that the rate of chondromucoprotein synthesis may be partially controlled by cell surface receptors.

Acetates↗

The incorporation and localization of aldehydes (highly reactive cigarette smoke components) into cellular fractions of cultured human lung cells.

WI 38 human fetal lung fibroblasts were incubated with tracer amounts of 14C-labeled formaldehyde and acetaldehyde which are highly reactive components of cigarette smoke. A pulse of 10 min with formaldehyde followed by a 60-min and 24-hr chase showed migration of 14C label into the nucleus. Fractionation of the nucleus revealed that the RNA fraction had the highest absolute and specific activity while the DNA and protein fractions contained considerably lower activities. All of the counts from formaldehyde were found in the adenine and guanine components of RNA. The DNA counts were distributed among adenine, guanine, and thymine. Incubation with 14C acetaldehyde showed a majority of the counts localized in the membrane plus nuclear lipid fraction. A small proportion of counts was found in the protein portion of the cells.

Acetaldehyde↗

The manipulated mesenchymal stem cells in regenerated skeletal tissues.

Ample experimental examples have been accumulated during the last 3 decades indicating the ability of exogenous sources of cultured cells to serve as implants accelerating cartilage regeneration in defects of articular surfaces. In some cases, the repair tissues form complete spatial reconstruction of the defect. In other cases, either the spatial reconstruction is incomplete or the quality of the reparative tissue is inadequate. A delayed pace of endochondral ossification in the deep zones of the subchondral region of the defects, or ossification above the tide mark, within the superficial cartilaginous articular regions have been noted. Therefore, even in this promising approach of biological resurfacing procedure results are not certain, and further investigative research efforts are required. In the current study, a comparison of implantations of various cultured cells of four different sources were tested in an avian system. The reparative tissue outcomes are divided into three grades: full regeneration success, partial success, and failure of regeneration according to qualitative histological parameters and quantitative observation of the gross specimen. Defects that failed to regenerate a completely filled lesion were found to contain cells carrying the preskeletal-precartilaginous characteristic marker of FGFR3. The findings based on the above parameters suggest that autogeneic, chondrocytic-enriched bone marrow derived mesenchymal cells are superior to other cell sources for articular cartilage regeneration. Grafting of defects with these cells results in a 100% success rate. Allogeneic limb bud-derived mesenchymal cells and allogeneic embryonal chondrocytes have both reached a success of 75% of completely filled defects. Allogeneic chondrocytic-enriched bone marrow-derived mesenchymal cells yielded a 31% success rate. Untreated defects completely failed to heal. In successfully healed defects no cells of the reparative tissue carry the FGFR3 marker 3 months postimplantation. In partially healed defects, FGFR3 positive staining is present in fibrous cells at the invaginated surface. These latest findings may suggest some kind of proliferation failure in such cases.

Animals↗

Characteristics of cartilage biopsies used for autologous chondrocytes transplantation.

Biopsies removed from 57 patients considered for cartilage transplantation were grown at CTI Ltd. (47 biopsies) and at Tel Aviv University (10 biopsies). Tissue processing took place in dedicated laboratories. Explant cultures allowed cell number expansion. Fifty-four out of 57 biopsies grew cells. Fanning out of the cells began after 5-15 days in culture. Two passages later, cell numbers in the 10(7) range were achieved. Cells from all cultures expressed mRNA of aggrecan and link protein but not of alkaline phosphatase. Histochemical stains such as alcian blue pH 1 were negative in sparse monolayer cultures, but positive in pellet cultures. Immunohistochemistry demonstrated expression of collagen type I in monolayer cultures, switching to collagen type II in micromass cultures. Fibroblast growth factor receptor 3, a recently described characteristic receptor of precartilaginous cells, was expressed in monolayers and disappeared in micromass cultures. In conclusion, explants of articular chondrocytes cultured in vitro consistently yield monolayer cultures. The cells appear to revert to dedifferentiated chondrocytes, expressing a mesenchymal stem cell protein profile. Simultaneously, these cells regained their capacity to proliferate. Cultures held as micromass allowed reexpression of the differentiated phenotype traits.

Aggrecans↗

Experimental septic arthritis in rabbits treated by a combination of antibiotic and steroid drugs.

OBJECTIVES: Intraarticular steroid injection is traditionally contraindicated during acute septic arthritis. However, there is abundant evidence which proves that the damage to the joint is not only due to the direct effect of bacteria, but also to the local protective mechanisms evoked by the organism. There is, therefore, theoretical justification for a combined therapy of systemic antibiotics and intraarticular corticostertoids in septic arthritis. METHODS: Experimental arthritis was induced by the intraarticular injection of Staphylococcus epidermidis in rabbits. The experimental scheme included three groups of animals: animals that were infected but not treated (group 1); animals treated with systemic antibiotics (group 2); and animals treated with systemic antibiotics and intraarticular steroids (group 3). Nine days later the animals were sacrificed and joint histopathological-histochemical indices were calculated. RESULTS: Animals from groups 2 and 3 had a smaller pannus, reduced proteoglycan loss, no loss of cartilage height and diminished synovial inflammation in comparison to the animals from group 1. The animals from groups 2 and 3 were identical in terms of cartilage cellularity, surface erosion, chondrocyte cloning, pannus formation and proteoglycan loss. Synovial inflammation appeared to be less pronounced in group 3 animals when compared to animals of group 2. CONCLUSION: Concomitant antibiotic-steroid treatment of septic arthritis seems to be harmless in this experimental setting.

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