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Biomedical subjects

G Stabellini

Publications and source records attributed to G Stabellini.

At least 37 records · Page 2Linked to original sources
PubMed1999

Ornithine decarboxylase in colonic mucosa from patients with moderate or severe Crohn's disease and ulcerative colitis.

Polyamines, as well as ornithine decarboxylase (ODC), the enzyme involved in their synthesis, were reported to be closely related to cell proliferation. In Crohn's disease and ulcerative colitis, cell destruction and proliferation increase in the active stage. The aim of the present study was to determine the ODC in both involved and uninvolved areas of the colonic mucosa of active Crohn's disease and ulcerative colitis patients. The patients were divided in two groups, owing to the different level of activity (severe or moderate), by means of clinical endoscopy, laboratory, and histology evaluations. Subjects with suspected disease, but endoscopically unconfirmed, were used as controls. In all ulcerative colitis and Crohn's disease patients the ODC values both in involved and uninvolved mucosa were significantly lower than in controls. In severe Crohn's disease ODC was significantly reduced versus moderate Crohn's disease only in affected tissues. In all ulcerative colitis patients (moderate or severe) the ODC was significantly decreased in involved mucosa compared with uninvolved mucosa. Severe ulcerative colitis showed the significantly lowest ODC. We suggest that the significant decrease of ODC in the bowel mucosa is closely related to the severity of the disease. The highest decrease of ODC in ulcerative colitis patients would be due both to the enhanced cell destruction, and to the feed-back from exogenous increased polyamine production (bowel bacteria, cell desquamation). Therefore ODC would be considered a sensitive index of the inflammatory derangement of the mucosa, especially in acute ulcerative colitis. We conclude that this behaviour may result in an enhanced risk of neoplasia.

Adult↗
PubMed1998

Exogenous spermidine modulates glycosaminoglycan accumulation and epithelial differentiation in chick embryonic skin.

We have previously shown that feather formation in chick embryonic skin depends on accumulation of sulphated glycosaminoglycans in the underlying mesenchyme, and that addition of spermidine to chick embryo fibroblasts increases the extracellular sulphated glycosaminoglycans. In the present work, using histological, histochemical and biochemical procedures, we have investigated the effects on glycosaminoglycan accumulation and on epithelial differentiation of adding spermidine and bis-cyclohexylammonium sulphate, a spermidine inhibitor, to embryonic chick skin cultures. Our results demonstrate that spermidine induces an accumulation of sulphated glycosaminoglycan and an increase in feather formation, suggesting that the morphogenetic effect of spermidine may be dependent on specific glycosaminoglycan accumulation.

Animals↗
PubMed1998

Relation between the osmolality trend and ornithynedecarboxylase activity in red blood cells of uremic patients during hemodialytic treatment.

In uremic patients during chronic hemodialysis an increase in the volume of red blood cells is observed. Contemporaneously there is an increase in intraerythrocytic ornithynedecarboxylase activity beyond the normal content (P < 0.01), a high level of seric and plasmatic polyamines (P < 0.01) and a decrease in seric osmolality (P < 0.01) with pH improvement. The trends of osmolality, ornithynedecarboxylase, mean cell volume and pH are significantly related. Our data support the hypothesis that, during hemodialysis, red blood cell volume changes and increased ornithynedecarboxylase activity are dependent on the general improvement of plasma tonicity. Moreover, the absence of inhibition of ornithynedecarboxylase activity by high levels of putrescine is noted.

Adult↗
PubMed1998

A contribution to the regulation of proteoglycan production: modulation by TGF alpha, TGF beta and IL-1 of glycosaminoglycan biosynthesis on beta-D-xyloside in chick embryo fibroblasts.

In order to elucidate the mechanisms determining the variability in the proteoglycan structure and the factors involved in this determination, we treated chick embryo skin fibroblasts with beta-D-xyloside to obtain glycosaminoglycan chains deprived of core proteins, and with different cytokines (transforming growth factor alpha and beta, interleukin-1) to produce variability. The different cytokines specifically regulate both cellular and extracellular amount and composition of glycosaminoglycans. Beta-D-xyloside treatment does not change protein content and protein synthesis, whereas it increases overall extracellular sulphated glycosaminoglycan production, heparan sulphate and chondroitin sulphate content, and reduces that of dermatan sulphate. This indicates that the core protein regulates quantitative proteoglycan production, and probably directs (with appropriate signals) the core oligosaccharide bound to it to the right synthesizing enzymes. The modulatory action of the different cytokines on sulphated glycosaminoglycan production and classes remains, even though the core protein is absent. This indicates that the cytokines also act on the glycosyltransferases. Our results suggest that the proteoglycan production may be subject to a double control, one of which is at the level of the core protein and the other, mediated by environmental signals, at the level of glycosaminoglycan synthesizing enzymes.

Animals↗
PubMed1998

DEHP-induced alterations in the lining tissue of the rat air pouch.

The direct effects of D(2-ethylhexyl)phthalate (DEHP), on subcutaneous tissue were studied in the rat, using the air pouch technique. Two ml of DEHP either undiluted or diluted in olive oil (10 microm/ml), were introduced into a previously created air pouch in the rats. The air pouch was removed and specimens of the lining tissue examined by optical and electron microscopy. The persistence of DEHP for 7 days is sufficient to cause alterations in the tissue. The major histological changes were the destruction of the tissue organization with cytoplasmic and nuclear alterations resulting in apoptotic bodies. The histochemical data showed an increase of sulphated glycosaminoglycans, showing proof of alterations in fibroblast functions. The authors suggest that the hyperplastic-type alteration induced by DEHP may be connected with the sclerosis of the peritoneal membrane described in uremic patients in CAPD.

Administration, Cutaneous↗
PubMed1997

Glycosaminoglycan analysis in amniotic fluid and in cultured fibroblasts from normal and holoprosencephalic human embryonic organs.

Glycosaminoglycans are polysaccharides involved in epithelial-mesenchymal interaction and cell differentiation and provide a meshwork which is essential to maintain a proper intercellular milieu. The development of embryonic organs can be accompanied by alterations in the glycosaminoglycan pattern. In pregnancies with malformed fetuses, there are alterations in total glycosaminoglycans and their components (chondroitin 4-6 sulphate, dermatan sulphate, and hyaluronic acid) in amniotic fluid. We examined total glycosaminoglycans and the percentage variations of the single classes in both amniotic fluid and culture medium of fibroblasts from heart, lung, and skin obtained from five normal human fetuses and one with holoprosencephaly. In the amniotic fluid total glycosaminoglycans and their sulphate classes were increased, whereas hyaluronic acid was decreased, compared with controls. The extracellular glycosaminoglycans showed hyaluronic acid reduction in skin, while chondroitin 4-6 sulphate plus dermatan sulphate and heparan sulphate were higher in skin and heart. Our data demonstrate that variations in the glycosaminoglycan pattern are associated with alterations of the cellular environment, which can prevent normal organogenesis.

Amniotic Fluid↗
PubMed1997

Involvement of polyamines in the action of transforming growth factor beta and interleukin-1 on cultured chick embryo fibroblasts.

In this study we have examined the relationship between growth factor-induced proliferation and ODC/polyamine levels. TGF beta promotes cell growth and enhances [3H]-thymidine incorporation in chick embryo fibroblasts maintained in a serum-depleted medium. The action on DNA synthesis declines in the second day of treatment. IL-1 does not affect proliferation or [3H]-thymidine incorporation either when it is added alone or in combination with TGF beta. The response of the cells to TGF beta is associated with a significant stimulation of ODC activity and Put, Spd levels together with an enhancement of the Spd/polyamines ratio. IL-1, which does not act on cell proliferation, fails to activate ODC and to increase polyamine levels, thus indicating that the ODC/polyamine system is most likely to be an important link in the chain of events that leads to growth factor-induced proliferation.

Animals↗
PubMed1997

Direct inhibitory effect of uremic toxins and polyamines on proliferation of VERO culture cells.

The dialysate fluid of uremic patients exhibits, in vitro, an inhibitory effect on cell growth, owing to urea, guanidino compounds, and substances named middle molecules. The polyamines are compounds which exhibit high levels in biological fluids during either normal development or disease such as psoriasis, uremia, and tumors. Dialysate and middle molecules show toxicity and degeneration of the organotype cultures, whereas the free polyamines and nonrecirculated dialysate do not have any toxic effect. The aim of this study is to analyze the effects of polyamines, nonrecirculated dialysate, and middle molecules of uremic patients in periodic hemodialysis on cultured VERO (fibroblast-like cells) growth. These cells show an inhibition of growth in middle molecules or 2 x 10(-4) M putrescine and a stimulation with nonrecirculated dialysate and 2 x 10(-8) M putrescine. The effect is different because the cultures with middle molecules begin growth again after 24 hr, whereas in the presence of 2 x 10(-4) M putrescine no further growth is observed. Cells maintained in middle molecules + 2 x 10(-8) M putrescine show an irreversible degeneration, attesting a toxic effect due to the low molarities of putrescine. The electron microscopy shows alteration of cytoplasmic, mitochondrial, and nuclear membranes, but no chromatin fragmentation with either middle molecules or 2 x 10(-4) M putrescine: this suggests that the cells do not die of apoptosis. In conclusion, during uremia the polyamines could cause toxic effects, even at low concentrations, on cells stressed by other toxic stimuli.

Animals↗
PubMed1997

Glycosaminoglycan metabolism and cytokine release in normal and otosclerotic human bone cells interleukin-1 treated.

Glycosaminoglycans (GAGs), normal components of the extracellular matrix (ECM), and the glycosidases, that degrade them, play a key role in the bone remodelling process. The effects of interleukin-1 alpha (IL-1 alpha) on GAG metabolism in normal and otosclerotic human bone cells as well as its capacity to modulate IL-1 alpha, IL-1 beta and IL-6 secretion in both populations was analyzed. The amount of radiolabeled GAGs was lower in otosclerotic than in normal bone cells. IL-1 alpha reduced newly synthesized cellular and extracellular GAGs in normal cells, but only those of the cellular compartment in otosclerotic bone cells. It depressed heparan sulphate (HS) more in normal cells and chondroitin sulphate (CS) more in otosclerotic bone cells. The HA/total sulphated GAG ratio was shifted in favour of the latter in otosclerotic cells, whereas the opposite effect was seen after IL-1 alpha treatment. There was little difference in the beta-D-glucuronidase levels of the normal and pathological cells, while beta-N-acetyl-D-glucosaminidase was significantly increased in otosclerotic bone cells. As the activity of neither enzyme was modified by treatment with IL-1 alpha, the cytokine seems to exert its influences on GAG synthesis rather than on the degradation process. IL-1 alpha, IL-1 beta and IL-6 secretion was markedly higher in otosclerotic cells. IL-1 alpha modulated the secretion of each interleukin differently, thus resulting in a cytokine cascade that may act in autocrine/paracrine manner on target cells. The authors suggest that changes in the cytokine network may have a specific, yet still unknown, role during normal and pathological osteogenesis.

Bone and Bones↗
PubMed1996

Collagen synthesis and cell growth in chick embryo fibroblasts: influence of colchicine, cytochalasin B and concanavalin A.

Culturing of chick embryo fibroblasts in the presence of colchicine or cytochalasin B with and without concanavalin A (Con A) demonstrated that colchicine induces greater neosynthesis of endocellular type I collagen, whereas cytochalasin B boosts secretion. The effects are modified by the addition of Con A, which increases alpha 2 more than a1 chain production. 3H-thymidine incorporation is unaffected by cytochalasin B, but stimulated by colchicine. Con A neutralizes the stimulatory action of colchicine. It would therefore seem that Con A exerts transmembrane control of effects induced by colchicine and cytochalasin B by binding to cell surface receptors and so triggering rearrangement of the cytoskeleton.

Actins↗
PubMed1996

Intracellular distribution of polyamines in human lymphoblastoid cell line during phorbol ester-induced differentiation.

Polyamines such as putrescine, spermidine and spermine play an important role in nucleic acid metabolism. These aliphatic amines display a key role in cell-induced transformation by carcinogen substances. In particular, one of these, the phorbol myristate acetate, provokes cell differentiation and gives an increase of ornithindecarboxylase activity; enzyme regulating the pathways of polyamines. In this study we analyse the trend of the polyamines at cytoplasmic and nuclear level during phorbol treatment. Our results show a correlation between nuclear and cytoplasmic spermine, 3H-Thymidine, 3H-Leucine incorporation and cell cycle phases. These data remark that the polyamines are differently distributed into the cell during the phorbol myristate acetate-mediated differentiation process and that the spermine is down-regulated for to supply the increased protein biosynthesis.

B-Lymphocytes↗
PubMed1996

Ultrastructural and histochemical features of the ground substance in cyclosporin A-induced gingival overgrowth.

The overgrowth-affected gingiva of patients treated with cyclosporin A after kidney transplant was examined with ultrastructural and histochemical methods to evaluate the involvement of connective tissue. Gingival overgrowth has the same clinical signs as local edema. The ultrastructural study showed that the dimensional increase was largely due to increased production of amorphous ground substance by fibroblasts, possibly resulting from an increased release of histamine by mast cells. The histochemical data revealed that the affected tissues contained higher levels of glycosaminoglycans and that cyclosporin A induced comparably high levels of glycosaminoglycans in in vitro cultures of fibroblasts obtained from normal gingiva. The combination of ultrastructural and histochemical data, therefore, strongly suggests that the response of the connective tissue in gingival overgrowth cannot be ignored and may be the main cause of the observed pathological condition.

Alcian Blue↗
PubMed1996

Analogs of cord red blood cell membrane components displayed on placenta, amnion and amniotic cells in culture.

Placenta and amnion were analyzed to ascertain the presence of antigens in common with red blood cells (RBC) from cord or fetuses. The expression of distinct antigens displayed on a subpopulation of cord RBC and detected by anticord RBC membrane antibodies was particularly investigated, concomitantly with the presence of transferrin receptors (TR) by employing immunohistochemistry. The placenta showed both cord antigen and TR; on the contrary, amnion--which was labelled by anti-cord RBC membrane antibodies--was not stained by the anti-TR antibody. The results of inhibition and double labelling assays further excluded TR as the relevant antigen in the labelling of both placenta and amnion. The staining of fetal membranes disappeared after absorption of antibodies with cord RBC membranes. These results suggest that the antigens externally expressed on a subpopulation of cord RBC are shared by amnion and placenta.

Amnion↗
PubMed1995

Polyamines and terminal deoxynucleotidyl transferase expression in KM 3 pre-B cell line during phorbol ester induced differentiation.

The aliphatic polyamines, putrescine, spermine and spermidine belong to a category of molecules implicated in DNA replication. Their synthesis is strongly activated during the G1 period and they have been implicated in the regulation of cell proliferation and differentiation. Terminal transferase is a DNA polymerase present in pre-T and pre-B cells and its expression can be modulated by phorbol ester treatment. In this study we have monitored the relationship of intracellular polyamine levels with terminal deoxynucleotidyl transferase down-regulation induced by 12-O-tetradecanoyl phorbol myristate 13-acetate treatment in the human pre-B KM-3 cell line. Phorbol myristate acetate can cause an increase, at 4 and 8 hours of differentiation, of intracellular levels of putrescine as well as a decrease in terminal deoxynucleotidyl transferase synthesis showing the probable involvement that polyamines have in the differentiation process.

B-Lymphocytes↗
PubMed1995

Heterogeneity of fibroblasts derived from human free and attached gingiva. Glycosaminoglycan synthesis and effects of phenytoin (PHT) treatment.

Two fibroblast populations derived from free and attached gingiva (FGF, AGF) have been compared in cell culture. They exhibited the same morphology and similar cytoskeletal staining patterns, but were different in glycosaminoglycan (GAG) synthesis. FGF released larger quantities of GAGs than AGF in the medium. The extracellular accumulation of hyaluronic acid was higher in FGF than in AGF, whilst the reverse pattern was observed intracellularly. In the case of sulphated GAGs the extracellular concentration, compared to HA, was higher in AGF, while the intracellular concentration was higher in FGF. The two cell populations responded differently to phenytoin (PHT) administration. PHT treatment increased the proportion of intracellular sulphated GAGs in AGF and of extracellular sulphated GAGs in FGF.

Adult↗
PubMed1995

Phenotype of in vitro human otosclerotic cells and its modulation by TGF beta.

A study was carried out to obtain a more detailed picture of the phenotypes of human otosclerotic and normal bone cells and to analyse the response of both populations to treatment with TGF beta 1. Total collagen synthesis was found to be decreased, but fibronectin secretion increased in otosclerotic with respect to normal cells. Although overall glycosaminoglycan (GAG) synthesis was lower in otosclerotic cells, the sulphated GAG to hyaluronic acid (HA) ratio was higher, in particular there was greater expression of chondroitin (CS) and dermatan sulphates (DS). TGF beta 1 induced a more marked increase in collagen and fibronectin release and greater production of sulphated GAGs as DS and heparan sulphate (HS) in the otosclerotic cells. The fact that the phenotype of the otosclerotic cells differed from that of the normal cells and could be modified by TGF beta 1 treatment, suggests that TGF beta 1 is implicated in the pathogenesis of otosclerosis.

Bone and Bones↗
PubMed1994

Effects of spermidine synthase inhibition on cytoskeletal organization in cultured chick embryo fibroblasts.

The administration of bis-cyclohexylammonium sulphate (BCHS), an inhibitor of spermidine synthase, to cultured chick embryo fibroblasts provoked alterations in cell morphology, a marked disorganization of microfilaments and changes in microtubule network structure. In addition, the rate of microtubule reappearance, after disrupting them with colchicine, was impaired by BCHS. These responses to BCHS were prevented by spermidine addition, which thus suggests an involvement of spermidine in microtubule and microfilament organization.

Actin Cytoskeleton↗