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Biomedical subjects

L Mantovani

Publications and source records attributed to L Mantovani.

At least 55 records · Page 3Linked to original sources
PubMed1993

Ofuji papuloerythroderma: report of a European case.

The trunk and the limbs of an 82-year-old man were covered with large sheets of flat-topped erythematous papules arranged in a reticulate pattern which suddenly coalesced assuming erythroderma-like aspects. Body and positional folds were characteristically spared (deck chair sign). Mild eosinophilia was present. The histological and immunohistochemical examinations revealed an unspecific eczematous pattern. After systemic steroids and PUVA treatment the patient recovered from the dermatosis. Papuloerythroderma is a distinctive clinical entity, but it is not clear whether the dermatosis is the skin marker of systemic pathological conditions or a precursor of cutaneous lymphomas.

Aged↗
PubMed1992

Membrane association and shedding of the GPI-anchored Ca-MOv18 antigen in human ovary carcinoma cells.

The antigen recognized by the MOv18 MAb (Ca-MOv18) was recently shown to be a glycosylphosphatidylinositol (GPI)-linked protein. In this report we show that GPI-anchorage is not limited to IGROVI cells nor to other ovary carcinoma cell lines, but Ca-MOv18 was also found to be sensitive to phosphatidylinositol-specific phospholipase C (PI-PLC) treatment on fresh ovarian cancer cells. Furthermore, we found a heterogeneous sensitivity of Ca-MOv18 to PI-PLC cleavage, not only among the different cells studied but also in different experiments performed on the same cell line, during extended periods of time in culture. Sensitivity to PI-PLC cleavage was determined by immunofluorescence on live cells and by double-determinant radioimmunoassay of the antigen released in the supernatant. The specificity of the PI-PLC cleavage was demonstrated as follows: (a) TX114 solubilized Ca-MOv18 shifts from the detergent to the aqueous phase after treatment with PI-PLC; (b) on membrane preparations, PI-PLC specifically released a fraction of the antigen, which is distinct from the weakly associated form released by high-salt treatment; (c) Ca-MOv18 from IGROVI expressed the cross-reacting determinant (CRD), which is characteristic of GPI-linked molecules. The absence of CRD expression on the spontaneously released protein and the possibility of artificially inducing antigen shedding during the resynthesis of Ca-MOv18 which follows bacterial PI-PLC treatment are interesting points which need to be further investigated in order to understand the physiology of the Ca-MOv18 tumor antigen.

Antibodies, Monoclonal↗
PubMed1991

Regulation of gene expression of macrophage-colony stimulating factor in human fibroblasts by the acute phase response mediators interleukin (IL)-1 beta, tumor necrosis factor-alpha and IL-6.

Fibroblasts constitute a major element of the bone marrow stroma. They play a pivotal role in blood cell development by providing the scaffolding required for cellular organization and tissue cohesion and by producing soluble molecules including colony stimulating factors (CSFs) and various interleukins regulating hematopoiesis. Our data demonstrate that the acute phase response mediators interleukin (IL)-1 beta, tumor necrosis factor (TNF)-alpha and IL-6 which are abundantly produced by activated monocytes, enhance levels of macrophage-colony stimulating factor (M-CSF) in fibroblasts by both transcriptional and post-transcriptional mechanisms. The action of these proteins to induce M-CSF transcript levels was dependent on synthesis of new proteins and was not mediated by protein kinase C (PKC) stimulation as depletion of cellular PKC pools by prolonged exposure of fibroblasts to phorbolester TPA did not prevent factor induced synthesis of M-CSF transcripts. However, blockade of PKC by the isoquinoline sulfonamide derivative H7 and thus inhibition of phosphorylation was associated with augmentation of the fibroblasts response to TNF-alpha and IL-6.

Fibroblasts↗
PubMed1991

Expression of leukemia inhibitory factor is regulated in human mesenchymal cells.

A protein variously termed leukemia inhibitory factor (LIF), differentiation-inducing factor, differentiation inhibitory activity or human interleukin for DA cells can control the differentiation and proliferation of hematopoietic cells as well as of several other cellular lineages. In order to further elucidate the spectrum of LIF-producing cells, we examined different cell types for the expression of LIF mRNA using Northern blot analysis. LIF mRNA was detected in activated normal human T-cells and in two T-cell lines but was undetectable in a B-lymphoid cell line, in both resting and activated normal human granulocytes and monocytes and in human myeloid cell lines K562 and HL-60. In human lung fibroblasts and in human umbilical vein endothelial cells, LIF was constitutively expressed and its accumulation was increased in a time-dependent manner following treatment with the phorbol ester TPA and in the presence of the two immediate response cytokines tumor necrosis factor (TNF)-alpha and interleukin (IL)-1-beta. We conclude that mRNA for LIF is not only expressed by T-cells but also in human mesenchymal cells. Expression of LIF transcripts in these cells is constitutive and can be significantly enhanced by phorbol ester, TNF-alpha and IL-1-beta.

Cells, Cultured↗
PubMed1990

Interleukin-6 (IL-6) is an intermediate in IL-1-induced proliferation of leukemic human megakaryoblasts.

We have examined the in vitro effects of recombinant human (rh) interleukin-1 (IL-1) on the growth of purified megakaryoblasts obtained from patients with acute megakaryoblastic leukemia. We demonstrate that both IL-1 alpha and IL-1 beta treatment of these cells led to stimulation of DNA synthesis (as shown by increase of 3H-thymidine incorporation up to 35-fold) and also resulted in colony formation of leukemic megakaryoblasts. However, the stimulatory effect of IL-1 was dependent on endogenous production of IL-6, because addition of neutralizing monoclonal antibody (MoAb) to IL-6 abrogated the stimulatory activity of IL-1. In contrast, neutralizing MoAbs to granulocyte (G)-colony stimulating factor (CSF), granulocyte-macrophage (GM)-CSF, and macrophage (M)-CSF failed to counteract the growth-enhancing effects of IL-1. Leukemic megakaryoblasts accumulated IL-6 mRNA and released IL-6 protein into their culture supernatant when exposed to rh IL-1 but failed to disclose transcripts for G-, GM-, and M-CSF under these conditions. Analysis of IL-6 receptor (IL-6R) transcript levels demonstrated that megakaryoblasts constitutively expressed IL-6R mRNA and that these transcripts are down-regulated to undetectable levels upon exposure to IL-1 and IL-6. Increase of 3H-thymidine incorporation by megakaryoblasts could be duplicated by exogenous IL-6 that could be blocked by neutralizing MoAb to IL-6. In conclusion, our results suggest that leukemic megakaryoblasts could produce and secrete IL-6, and express IL-6R, and that the growth-enhancing effect of IL-1 on these cells is indirect, via production of IL-6 by leukemic cells.

Antibodies, Monoclonal↗
PubMed1990

The Ca-MOv18 molecule, a cell-surface marker of human ovarian carcinomas, is anchored to the cell membrane by phosphatidylinositol.

The structure of the 38 kD cell surface glycoprotein identified by the monoclonal antibody MOv18 and specifically expressed by human ovarian carcinomas has been investigated at a molecular level. The ovarian carcinoma cell line IGROV-1, which expresses high levels of Ca-MOv18, was treated with the phosphatidylinositol-specific phospholipase C from B. thuringiensis. The phospholipase C specifically released most of the Ca-MOv18 molecules as shown by flow cytometric analysis of the treated cells and by radioimmunometric assays of the corresponding supernatants. Consistent with the known structure of other phosphatidylinositol-linked molecules, Ca-MOv18 was biosynthetically labeled by [3H]ethanolamine and the labeled molecules were immunoprecipitated from the supernatant fo the phospholipase C treated cells. Evidence that Ca-MOv18 is anchored to the cell membrane via phosphatidylinositol may prove to be relevant in current investigations regarding the biological and clinical significance of this tumor marker.

Antibodies, Monoclonal↗
PubMed1990

Differential regulation of interleukin-6 expression in human fibroblasts by tumor necrosis factor-alpha and lymphotoxin.

The treatment of human diploid fibroblasts with tumor necrosis factor (TNF)-alpha and with lymphotoxin (LT) is associated with induction of interleukin-6 (IL-6) transcripts with TNF-alpha being 10-fold more potent than LT. Here we report on the TNF-alpha/LT-induced signaling mechanisms responsible for the regulation of IL-6 gene expression in these cells. Run-on assays demonstrated that both TNF-alpha and LT increase IL-6 mRNA levels by transcriptional activation of this gene. Stability studies of IL-6 transcripts in fibroblasts showed that TNF-alpha delayed IL-6 mRNA decay but not LT. The induction of IL-6 transcripts by TNF-alpha and LT was not inhibited by the isoquinoline sulfonamide derivative H7. Similarly, depletion of protein kinase C (PKC) by 12-O-tetradecanoyl-phorbol 13-acetate (TPA) did not change the ability of TNF-alpha and LT to induce IL-6 transcripts, demonstrating that stimulation by these agents may not be mediated by activation of PKC. Stimulation of IL-6 transcripts in fibroblasts did also not require new protein synthesis as exposure to the protein synthesis inhibitor cycloheximide (CHX) enhanced accumulation of IL-6 mRNA in the presence or absence of TNF-alpha or LT.

Cells, Cultured↗
PubMed1990

Interleukin-4 regulates mRNA accumulation of macrophage-colony stimulating factor by fibroblasts: synergism with interleukin-1 beta.

We demonstrate that macrophage-colony stimulating factor (M-CSF) is expressed in human fibroblasts at the mRNA and protein level. Following activation with both interleukin (IL)-1 beta and IL-4, fibroblasts synthesized M-CSF transcripts detectable by Northern blot analysis with peak expression occurring at 8 h and 12 h, respectively. Exposure of fibroblasts to both cytokines resulted in M-CSF protein release at 60 h of c. 500 U/ml (for IL-1 beta) and 1000 U/ml (for IL-4), relative to a control preparation of recombinant human M-CSF in a murine bone marrow colony assay. Both interleukins synergized to enhance M-CSF mRNA accumulation and their ability to induce M-CSF transcripts could be abolished by treatment with specific neutralizing antibodies. These observations provide support for the idea that fibroblasts may control monocyte/macrophage development and function, and that IL-1 beta and IL-4 are involved in the regulation of this process.

Blotting, Northern↗
PubMed1990

Evaluation of the immunoreactive fraction of an anti-tumour monoclonal antibody.

Over a period of approximately 1 year, the immunoreactivity of the anti-ovary carcinoma MAb MOv18 was evaluated after radiolabelling with 125I on two different ovarian carcinoma cell lines, OvCa432 and IGROV1. A high variability of the immunoreactive values was observed by analysing different preparations of radiolabelled MOv18 (from 12 to 21% on OvCa432 and from 22 to 56% on IGROV1) and by using the same radiolabelled preparation (12% on OvCa432 and 51% on IGROV1). Since the variability could be due to the target cells, we set up an alternative binding assay using the anti-idiotypic MAb anti-Id18.1 directed against a private idiotype closely associated with the MOv18 paratope. Three different experiments carried out with the anti-idiotypic MAb gave reproducible results with an immunoreactive range from 71 to 83%. A direct comparison between the reactivity of the same 125I-MOv18 preparation on anti-Id18.1 and on IGROV1 confirmed the higher value of the immunoreactive fraction estimated on the more homogeneous anti-idiotypic reagent (71%), rather than on the tumour cells (56%). These data suggest that anti-idiotypic MAbs could represent suitable reagents for the evaluation of the immunoreactivity of an antibody preparation after radiolabelling and before in vivo administration.

Antibodies, Anti-Idiotypic↗
PubMedDate not supplied

A double determinant radioimmunoassay Mov2-MOv8 for monitoring ovarian carcinomas: definition of the methodology.

A double-determinant radioimmunoassay for the detection of circulating antigens associated with human ovarian carcinoma was developed using two monoclonal antibodies: MOv2 and MOv8 employed respectively as catcher and tracer. The development of the method through three different procedures enabled us to detect the presence of CaMOv2-CaMOv8 carrying molecules in 14 out of 15 ascitic fluids from ovarian carcinoma patients whose tumors were found to be positive with MOv2 and MOv8 monoclonal antibodies by immunofluorescence. Moreover, 13 out of 15 ovarian carcinoma patients presented high levels of antigen in their serum (60-170 Ua/ml). Low levels of antigen were observed in the normal population, the values ranging from 30-40 Ua/ml. However, in 13 out of 100 apparently healthy women high levels of antigen were found in the serum.

Adult↗
PubMedDate not supplied

Detection of Lewis(a) antigen in sera of ovarian carcinoma patients by MOv2-MOv8 double-determinant radioimmunoassay.

The monoclonal antibodies MOv2 and MOv8, raised against ovarian carcinoma, were found to be directed against two non-crossreacting epitopes expressed on the same molecule. Immunochemical analysis of the MOv8 recognized epitope showed that the Le(a) oligosaccharide, or commercial anti-Le(a) MAb, but not the anti-Le(b) MAb, prevented Ov8 binding to the reference target cell line (SW626), indicating that it is carried by the Le(a) antigen. Since we previously reported that MOv2 also recognises the Le(a) antigen, these data suggest that Mov8 and Mov2 were directed against different epitopes on the same oligosaccharide chain. Bearing in mind the knowledge of the biochemical nature of the monoclonal antibody recognized epitopes (CaMOv2 and CaMOv8), the presence of the circulating molecules recognized by them was analyzed by double determinant immunoradiometric assay (DDIRMA) in 103 sera from ovarian carcinoma patients. Patients with clinical evidence of the disease (ED) with MOv2 and MOv8 reactive and negative tumors had sera reactivity in 67% and 19% respectively. Also, 26% of the patients with no clinical evidence of disease (NED) had positive sera. When we investigated the relationship between MOv2-MOv8 DDIRMA sera positivity and red blood cells (RBC) Lewis phenotype, a strong correlation was found between the Le(a)+ phenotype and DDIRMA sera reactivity in healthy donors (6/6) and in ovarian carcinoma patients (9/10) whatever their clinical condition. No Le(a)- healthy donors gave evidence of MOv2-MOv8 reactive sera. In contrast, 33% and 57% of the sera from ED carcinoma patients with respectively Lea-b+ and Lea-b- phenotype were positive.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMedDate not supplied

Contact sensitization to corticosteroids: increased risk in long term dermatoses.

Patients affected by chronic dermatoses are at high risk for the development of sensitization to corticosteroids. This study was carried out to evaluate contact hypersensitivity to corticosteroids in a selected group of patients affected by longlasting cutaneous dermatoses. Sixty subjects underwent the GIRDCA series. The Italian GIRDCA series we applied had the following substances in addition to the European standard series: imidazolidinyl urea 2% pet, thiomersal 0.1% pet, disperse yellow 31% pet, disperse red 1% pet, 4'4-diaminodiphenylmethane 0.5% pet, ammoniated mercury 1% pet. The patients were tested with our corticosteroids series and some of them also with their own steroid products. Allergic reactions to corticosteroids were observed in 8/60 (13.3%) patients; budesonide was the main sensitizer (7 positives) followed by hydrocortisone-17-butyrate and betamethasone-17-valerate (2 and 1 positives, respectively). One patient also reacted to methylprednisolone aceponate contained in her own cream. 4/8 positives were certainly related to previous drug-exposure. This study showed a very high percentage of sensitization to corticosteroids. In our opinion, this value may be due both to our selection-standards and to the wide employment of a well known sensitizer like budesonide in our country. Although a corticosteroids series like ours seems to be adequate for the detection of sensitized patients, patch tests with individual compounds and/or steroids corresponding to local prescription habits are recommended, especially in unresponsive chronic dermatoses.

Administration, Topical↗