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M Melis

Publications and source records attributed to M Melis.

At least 19 recordsLinked to original sources
PubMed1995

Is there a role for adjuvant immunochemotherapy after radical nephrectomy in pT2-3N0M0 renal cell carcinoma?

Five-year overall survival after radical surgery in N0M0 renal cell carcinoma varies from 45-80% in pT2 to 35-50% in pT3 categories. In view of the alpha interferon and vinblastine combination which has shown some activity in advanced disease with increasing efficacy in limited metastatic invasion, we decided to explore the theoretical advantage of adjuvant chemo-immunotherapy in radically resected stage II, III renal cell carcinoma. A single-institution phase II study was undertaken to evaluate the efficacy and tolerability of alpha 2a-interferon (alpha 2a-INF) in combination with vinblastine in 30 patients with pT2-T3 N0M0 renal cell carcinoma (RCC). Thirty-two patients who received only radical nephrectomy and extended lymphadenectomy were analyzed and results were compared with the first group. Twenty-three of 30 (76.6%) patients in the first group are alive with no evidence of disease. The median follow-up for the 23 patients still alive was 67 months (range 60 to 72). Metastases were documented in 5 patients (16.6%) with a median interval to progression of 24 months. Four of them (13.6%) died of tumor. In the control group, 16 out of 32 patients (50%) are still alive, with a median follow-up for the patients still alive of 62 months (range 60 to 68). Fifteen patients developed distant metastases and 2 of them had a local recurrence. All of them (46.8%) died of tumor. Median progression interval was 24 months. After stratification by pathological grade, site, laterality and number of nodes found at lymphadenectomy there were no statistical differences in risk of progression or death in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗
PubMed1994

Mononuclear cells in exudative malignant pleural effusions. Characterization of pleural phagocytic cells.

The aims of this study were to develop a methodology for the isolation of highly enriched mononuclear phagocyte populations from exudative malignant pleural effusions (EMPE) and to characterize the phenotype and functional properties of these cells. Pleural effusion mononuclear cells (PEMC) were isolated by Ficoll centrifugation of EMPE and transudative pleural effusions and allowed to adhere to plastic for 1 h to obtain a pleural effusion mononuclear adherent cell (PEMAC) fraction. Only 66.0 +/- 4.2 percent of PEMAC ingested latex particles, indicating that a significant proportion of PEMAC were not phagocytic cells. Latex-positive PEMAC had the morphologic appearance of macrophages and stained positive (97.3 +/- 4.3 percent) with the anti-CD68 monoclonal antibody (MoAb), specific for macrophages. Conversely, latex-negative PEMAC (34.0 +/- 4.1 percent of PEMAC) did not react with the anti-CD68 MoAb and stained with anti-CD3 (34.7 +/- 10.7 percent) and anticytokeratin (50.5 +/- 16.4 percent) MoAbs, indicating that T cells and mesothelial cells were present in the PEMAC fraction. To improve the purification of pleural macrophages, PEMAC were cultured for an additional 18 h and the cells that remained adherent after this period constituted the firmly adherent mononuclear cell (FAMC) fraction. Nearly 90 percent of FAMC ingested latex particles and were CD68-positive. Virtually all FAMC were CD3-negative and cytokeratin-negative. Similar percentages of FAMC from EMPE and transudative effusions expressed the monocyte-lineage markers CD11b and CD14, suggesting that the proportion of monocyte-like mononuclear phagocytes in the pleural space is not increased during local tumor-associated inflammatory responses. The FAMC from EMPE (1) expressed HLA-DR antigens, (2) released interleukin 1 (IL-1) beta and tumor necrosis factor (TNF) alpha, and (3) stimulated allogeneic T-lymphocyte proliferation. The results of this study suggest that pleural mononuclear phagocytes may be involved in tumor-associated inflammatory reactions in the pleural compartment by stimulating the proliferation of other inflammatory cells and by releasing inflammatory cytokines.

Aged↗
PubMed1992

The monoclonal antibody ER-BMDM1 recognizes a macrophage and dendritic cell differentiation antigen with aminopeptidase activity.

Here we describe the reactivity of monoclonal antibody (mAb) ER-BMDM1, directed against a 160-kDa cell membrane-associated antigen (Ag) with amino-peptidase activity. The aminopeptidase recognized by ER-BMDM1 is present on various mouse macrophage (M phi) and dendritic cell (DC) subpopulations as well as on microvillous epithelia. Analysis of ER-BMDM1 Ag expression in in vitro models of M phi maturation revealed that the Ag is expressed at increasing levels upon maturation of M phi. In vivo, high level expression of the ER-BMDM1 Ag occurs after the monocytic stage of maturation, since bone marrow cells and peripheral blood monocytes are essentially ER-BMDM1 negative. Analysis of isolated-resident and elicited M phi populations showed that ER-BMDM1 recognizes a specific subpopulation of mature M phi: only some resident peritoneal and alveolar M phi are ER-BMDM1 positive, whereas virtually all thioglycollate-elicited peritoneal exudate M phi bind the mAb. In lymphoid organs, a subpopulation of M phi is recognized as well as interdigitating cells (IDC) located in T cell areas. Phenotypic analysis of isolated DC--the in vitro equivalents of IDC--from spleen and lymph nodes confirmed that the majority of this important antigen-presenting cell population expresses the ER-BMDM1 aminopeptidase. The molecular characteristics of the ER-BMDM1 Ag suggest that it may represent the mouse homolog of human CD13.

Aminopeptidases↗
PubMed1992

Antitumour activity of mononuclear phagocytes: role of tumour necrosis factor alpha.

Tumour necrosis factor alpha (TNF) is a cytokine produced by mononuclear phagocytes (MP) originally discovered for its cytotoxic activity on tumour cell targets. It was subsequently demonstrated that, in addition to its oncolytic potential, TNF exerts a wide variety of activities on the host defensive system against malignancies. This article briefly reviews the current concepts on the role of TNF in the antitumour activity of MP.

Cytotoxicity, Immunologic↗
PubMed1991

High-performance liquid chromatographic determination of dinitroaniline herbicides in soil and water.

A high-performance liquid chromatographic method for the simultaneous determination of the dinitroaniline herbicides dinitramine, ethalfluralin, trifluralin, pendimethalin and isopropalin in soil and surface water is reported. The soil was extracted with diethyl ether and analysed without any clean-up. The water was analysed after purification and concentration on a C18 cartridge. The average recoveries were in the range 89-104%. The detection limits for the five herbicides were 0.02 mg/kg in dry soil and 0.5 micrograms/l in surface water.

Aniline Compounds↗
PubMed1991

Effect of indomethacin on the kinetics of tumour necrosis factor alpha release and tumour necrosis factor alpha gene expression by human blood monocytes.

In this investigation we have examined the effects of indomethacin, an inhibitor of the cyclooxygenase pathway of arachidonic acid, upon the kinetics of the release of tumour necrosis factor alpha (TNF) and of the expression of TNF gene by lipopolysaccharide (LPS)-stimulated human blood monocytes (BM). Following stimulation of BM with LPS, TNF was released within 2 h, reached peak values at 8 h and declined at subsequent time-points (24 and 48 h). Indomethacin (10(-5) M) slightly stimulated the production of TNF at 2, 4, and 8 h and prevented the decline of TNF observed at 24 and 48 h. This effect was related to the persistence of TNF synthesis, as demonstrated by kinetic evaluation of the expression of TNF gene performed by dot-blot analysis. The effects of indomethacin on TNF release and TNF gene expression were due to the inhibition of endogenous prostaglandin (PG)E2 production. In the absence of indomethacin, PGE2 release by the LPS-stimulated BM began concomitantly with the decline of TNF production by the same cells under the same stimulus. Indomethacin completely blocked PGE2 release at any time-point. Exogenous PGE2 suppressed the release of TNF and the expression of TNF gene in a dose-dependent fashion. Exogenous PGE2 completely reversed the effects of indomethacin on TNF production at 24 h. These findings suggest that indomethacin may significantly alter the kinetics of TNF release and TNF gene expression by LPS-stimulated BM. These effects are related, at least in part, to the inhibition of the production of endogenous PGE2, an important self-driven regulatory factor of the kinetics of TNF production.

Dinoprostone↗
PubMed1991

Increased expression of leukocyte function associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) by alveolar macrophages of patients with pulmonary sarcoidosis.

Leukocyte function associated antigen-1 (LFA-1) and its ligand intercellular adhesion molecule-1 (ICAM-1) are cell adhesion molecules that play an important role in the capacity of monoculear phagocytes (MPs) to present antigens to T lymphocytes. Since in pulmonary sarcoidosis (PS) this capacity is increased at sites of disease activity, we studied the expression of LFA-1 and ICAM-1 on peripheral blood monocytes (BMs) and alveolar macrophages (AM) obtained by bronchoalveolar lavage (BAL) from normal subjects (n = 7) and patients with PS (n = 14). To accomplish this, immunocytochemical stainings were made on cytocentrifuge preparations using anti-LFA-1 (anti-CD 11a) and anti-ICAM-1 (anti-CD 54) monoclonal antibodies (MoAbs). Normal and sarcoid BMs displayed a high percentage of positivity with both MoAbs with no difference between study groups (LFA-1: control BM 87.8 +/- 8.8 percent; sarcoid BM 84.7 +/- 9.5 percent; ICAM-1: control BM 80.8 +/- 10 percent; sarcoid BM 88.0 +/- 4.2 percent; p = NS for all comparisons). In both groups the percentage of cells expressing LFA-1 and ICAM-1 molecules among AMs was lower than among autologous BMs (LFA-1: control AM 46.5 +/- 13.2 percent, p less than 0.001 vs control BM; sarcoid AM 64.2 +/- 15.9; p less than 0.001 vs sarcoid BM) (ICAM-1: control AM 42.7 +/- 8.5 percent, p less than 0.001 vs control BM; sarcoid AM 72.1 +/- 10.6, p less than 0.001 vs sarcoid BM). AMs from patients with PS showed a higher degree of positivity for LFA-1 and ICAM-1 than normal AMs (p less than 0.02 and p less than 0.001, respectively). The positivity for LFA-1 and ICAM-1 molecules on sarcoid AMs was not correlated with the positivity for two different BM-associated markers (ie, the CD 11b and the CD 14 molecules) and was not correlated with the percentage of T lymphocytes in BAL, selected as a marker of the intensity of the alveolitis. These results suggest that the increased ability of sarcoid AMs to induce the proliferation of T lymphocytes may be related, at least in part, to the increased expression of LFA-1 and ICAM-1 molecules on their surfaces.

Antigen-Presenting Cells↗
PubMed1991

Scanning electron microscopy observations of nasal mucosa in patients affected by retinitis pigmentosa.

A controlled study of the ciliated epithelium of olfactory mucosa was performed on 25 patients affected by retinitis pigmentosa and in 5 healthy subjects. Scanning Electron Microscopy showed a significant lack of ciliated epithelial cells. These cells probably represent undifferentiated ciliated cells. These morphological alterations of the olfactory mucosa might correspond to similar changes in the outer segment of retinal photoreceptors in retinitis pigmentosa.

Humans↗
PubMed1991

[Monitoring of erection function in patients with prostatic carcinoma treated with Casodex].

This study evaluates the sleep-related erections in 5 patients with locally advanced prostate cancer (T3NOMO) during 6 months treatment with Casodex by multinight continuous monitoring of penile tumescence and rigidity. Mean serum LH, Testosterone and Estradiol levels shown a no statistically significant increase at the six months control. We found no significant modifications in the number of NPT episodes, maximum penile circumference and rigidity time before and after therapy. Penile arterial flow and neurologic examination were also unmodified. All patients had a stable disease and unchanged performance status after 6 months. This pure antiandrogen in a men with prostate cancer does not seem to interfere with self reported libido and erectile capability.

Androgen Antagonists↗
PubMed1990

Determination of heavy metals in animal tissues.

During studies on the accumulation of heavy metals in animal organs and tissues, only small samples (0.5-2 g) rich in lipids and having low concentrations of metals are often available. This may lead to loss of metals in the various steps of the analytical procedure. A modified procedure of mineralization for the determination of Pb, Cd and Zn is described, as well as suitable analytical procedures used by the Authors for the determination by atomic absorption spectrophotometry. Results showed that the loss of metals is minimized with these procedures.

Animals↗
PubMed1990

Murine macrophage precursor characterization. I. Production, phenotype and differentiation of macrophage precursor hybrids.

This study reports on the earliest stages of mononuclear phagocyte differentiation. A crucial question in this developmental process is whether mature macrophage (M phi) heterogeneity is already appointed at the precursor cell level. For this purpose, we produced clonal populations of mononuclear phagocytes from bone marrow culture by somatic cell hybridization with two hypoxanthine, aminopterin, thymidine-sensitive myeloid cell lines. A panel of 22 stable hybrids was obtained from these fusions. Differentiation stage analysis of the hybrids indicated that all cell lines had immature mononuclear phagocyte characteristics. The hybrids exhibited typical myeloid morphology and mainly nonadherent growth. Mature M phi features, such as expression of the cell surface antigens Mac-1, Mac-2 and F4/80, phagocytosis of latex beads, and expression of nonspecific esterase and acid phosphatase activity, were virtually absent. The immature M phi markers Thy-1, MIV25 and MIV52, on the other hand, were readily expressed, although heterogeneity was observed among different hybrid cell lines. We then analyzed the differentiation potential of seven hybrids by culture of the cells in the presence of post-lipopolysaccharide serum supplemented with interferon-gamma and found that the expression of mature M phi characteristics was induced. However, the various hybrids showed divergent patterns of mature M phi marker induction. R0C2 cells, for instance, showed extensive morphological and phenotypical differentiation without concomitant induction of phagocytosis. In contrast, W1C4 cells showed significant induction of phagocytosis without simultaneous increase of phosphatase and esterase activity. R1C1 cells were unique in the strong induction of Ia antigen expression. Together, our data indicate that (a) early M phi differentiation stages can be rescued by somatic cell hybridization, and that (b) the obtained cell lines are able to mature according to divergent differentiation programs.

Acid Phosphatase↗
PubMed1990

Murine macrophage precursor characterization. II. Monoclonal antibodies against macrophage precursor antigens.

The aim of the present study was the phenotypical analysis of early stages in macrophage (M phi) differentiation. For this purpose, we produced a panel of syngeneic rat hybridomas, which secreted antibodies (mAb) against M phi precursor antigens. As immunogens we used immortalized M phi precursors (P.J. M. Leenen et al., Eur. J. Immunol. 1990, 20: 15). We screened the obtained mAb in the following in vitro models of M phi differentiation: (a) a panel of M phi cell lines ordered in a linear differentiated sequence; (b) immature and mature mononuclear phagocytes obtained from bone marrow (BM) culture; (c) a panel of M phi precursor hybrids, and (d) differentiated and control M phi precursor hybrid cells. Four mAb, ER-MP12, ER-MP20, ER-MP54 and ER-MP58, were selected. These mAb recognize antigens which disappear in the course of M phi differentiation. Next, we investigated whether these mAb also recognized M phi precursors in normal BM. For this purpose, ER-MP-positive and -negative BM fractions were isolated using a fluorescence-activated cell sorter. Fractions were cultured in M phi-colony-stimulating factor-containing conditioned medium, and the resulting mature M phi progeny was quantified using the MTT assay. The present experiments indicate that ER-MP12 and ER-MP20 detect a subpopulation of BM M phi precursors, whereas ER-MP58 stains virtually all M phi precursors. Biochemical analysis of radioiodinated antigens revealed that these mAb recognize different molecules. ER-MP12 and ER-MP20 bound to single-chain (glyco)proteins of 140 kDa and 14 kDa, respectively. ER-MP54 precipitated multiple polypeptides, of which the major chains have an apparent molecular mass of 90, 80-85 and 70-75 kDa. Based on the molecular mass of the recognized antigens and the mAb specificities we conclude that ER-MP12, ER-MP54 and ER-MP58 recognize hitherto unknown antigens of murine M phi precursor cells. The antigen detected by ER-MP20 is most likely identical to Ly-6C.

Animals↗
PubMed1990

Differential inhibition of macrophage proliferation by anti-transferrin receptor antibody ER-MP21: correlation to macrophage differentiation stage.

Monoclonal antibodies (mAbs) directed against the transferrin receptor are known to inhibit proliferation of cells due to iron deprivation. Some cell types, however, escape from growth inhibition by a mechanism which is unclear at present. This mechanism is the subject of the present study. We investigated the differential growth inhibition caused by anti-transferrin receptor mAb ER-MP21 in connection with the differentiation of murine macrophages (M phi). Therefore, we applied two models of M phi differentiation, namely, culture of bone marrow cells in the presence of M-CSF and a panel of M phi cell lines ordered in a linear differentiation sequence. In both models we observed that proliferation of M phi precursors was strongly inhibited by ER-MP21. In contrast, proliferation of more mature stages of M phi differentiation was hardly affected. Remarkably, iron uptake by M phi precursor and mature M phi cell lines was inhibited by ER-MP21 to the same extent. However, mature M phi cell lines showed an iron uptake two- to threefold higher than that of M phi precursor cell lines. These observations strongly suggest that mature M phi escape from ER-MP21-mediated growth inhibition, because these cells take up more iron than is actually needed for proliferation. Furthermore, we found that enhanced iron uptake by mature M phi is not necessarily accompanied by a higher cell surface expression of transferrin receptors, thus suggesting an increased recycling of transferrin receptors in mature M phi.

Animals↗
PubMed1990

[Winging effect in interatrial defect after transseptal mitral valvuloplasty: an anatomical study].

In the balloon catheters the redundancy of the deflated balloon produces 2 or 3 sort of thin wings. The presence of wings can reduce the catheter "pushability" or, in certain conditions, can determine tissue lesion (winging effect). Simulating a transeptal valvuloplasty of the mitral valve by technique of the 2 balloon in human fresh heart, we studied the winging effect over the interatrial septum in 12 hearts; in the first 6 the atrial septum was dilated with a 6 mm balloon (Group A), in the second 6 the atrial septum was dilated with a 10 mm balloon (Group B). The procedure was completed introducing consecutively 2 bigger balloons (15 + 20 mm). We suppose that the winging effect of the 2 bigger balloons (15 + 20 mm) could counter balance the theoretical advantage of a small balloon (6 mm). The atrial septal defect (ASD) after septal dilatation was 5.0 +/- 0.59 mm x 1.56 +/- 0.25 mm (long axis x short axis) in Group A and 6.53 +/- 0.35 x 2.16 +/- 0.39 mm in Group B (p less than 0.01). The final ASD (after introducing the 2 bigger balloons) was 7.04 +/- 1.06 x 2.36 +/- 0.57 mm in Group A and 7.03 +/- 0.18 x 2.16 +/- 0.32 mm in Group B (NS). Our data show that the winging effect can determine biological negative effects.

Catheterization↗
PubMed1989

Lung compartmentalization of increased TNF releasing ability by mononuclear phagocytes in pulmonary sarcoidosis.

The TNF is a monokine with cytotoxic and tumor-necrosing activities; in addition, TNF may play a role in inflammatory processes. The present study evaluates spontaneous and LPS-mediated release of TNF by AMs and autologous peripheral BMs of normal subjects and patients with pulmonary sarcoidosis. A recently developed cytotoxicity assay, specific for detection of TNF activity, was applied. This study demonstrates that (1) unstimulated mononuclear phagocytes released low levels of TNF with no differences between groups; (2) when effector cells were stimulated with LPS, AMs from patients with active pulmonary sarcoidosis released more TNF than AMs recovered from normal subjects and from patients with inactive disease; (3) this increase was compartmentalized to the lungs, since comparisons of TNF production by LPS-stimulated BMs failed to show any difference between study groups. These results suggest that TNF might play a role in the pathogenesis of the alveolitis of pulmonary sarcoidosis.

Adult↗