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Biomedical subjects

F Indiveri

Publications and source records attributed to F Indiveri.

At least 55 records · Page 3Linked to original sources
PubMed1997

The presence of posttransplant HLA-specific IgG antibodies detected by enzyme-linked immunosorbent assay correlates with specific rejection pathologies.

Posttransplant monitoring of anti-HLA antibodies with routine techniques gives unsatisfactory results due to a variety of technical limitations. We investigated how a new alternative technique correlates with posttransplant clinical events. A total of 313 nonselected serum samples from 136 patients were screened by an ELISA utilizing captured soluble HLA class I antigens. We observed the absence of anti-HLA antibody production in acute rejection cases responding to standard antirejection therapy. On the other hand, we showed a clear presence of these antibodies in acute rejection episodes not responding to standard therapy (P<0.0001) and in chronic rejection (P<0.001). We conclude that routine posttransplant monitoring by ELISA offers early risk assessment that is crucial for proper immunosuppression and for antirejection therapy choice.

Cytotoxicity, Immunologic↗
PubMed1997

L-tyrosine and nicotine induce synthesis of L-Dopa and norepinephrine in human lymphocytes.

Catecholamines (CA) were studied in peripheral human lymphocytes in basal conditions as well as after L-tyrosine and/or acetylcholine (ACh) stimulation. Nicotinic and muscarinic receptor activation and blockade were assessed. CA were determined after ultrasonic cell disruption in peripheral lymphocytes after incubation (1 h at 37 degrees C) with the chemicals employed. L-tyrosine significantly increased (P < 0.01) L-Dopa and norepinephrine (NE) content of lymphocytes. ACh in the low microM range did not modify, whereas ACh (60 microM) and (120 microM) significantly increased (P < 0.01), both L-Dopa and NE intracellular levels. L-tyrosine plus ACh (60 microM) or (120 microM) significantly increased (P < 0.01) intracellular L-Dopa and NE versus control, versus L-tyrosine alone and versus ACh alone. The increase was higher than the algebraic sum of the individual increases. Nicotine (250 microM), but not muscarine (50 microM), significantly increased L-Dopa and NE in lymphocytes. Tetraethylammonium (500 microM) (nicotinic blocker), but not atropine (100 microM) (muscarinic blocker), inhibited the ACh-mediated increase of intracellular L-Dopa and NE. These data show that lymphocyte synthesis of CA is under nicotinic control. Since intracellular L-Dopa after L-tyrosine plus ACh increased 6-fold versus basal, 2-fold versus L-tyrosine alone and 3-fold versus ACh alone, it is concluded that ACh might regulate CA synthesis in lymphocytes through an activation of the rate limiting enzyme tyrosine hydroxylase.

Acetylcholine↗
PubMed1997

S-adenosil-L-methionine is able to reverse the immunosuppressive effects of chenodeoxycholic acid in vitro.

The study was conceived to evaluate if S-adenosil-L-methionine, a substance commonly used in the treatment of cholestasis in patients with cirrhosis and chronic hepatitis, exerts any immunological effect and of it is able to counterbalance bile acid-mediated immunosuppression. Proliferation and interleukin 2 and interferon-gamma secretion of human lymphocytes, collected from healthy subjects and exposed to mitogenic stimuli (phytohemagglutinin, pokeweed and anti-CD3 monoclonal antibodies), were analysed in the basal condition or after exposure to S-adenosil-L-methionine and/or chenodeoxycholic acid. Chenodeoxycholic acid inhibited phytohemagglutinin-induced lymphocyte proliferation and interferon-gamma secretion, and phytohemagglutinin and pokeweed-mediated interleukin 2 secretion. S-adenosil-L-methionine did not affect lymphocyte proliferation while it reduced interleukin 2 secretion upon phytohemagglutinin and pokeweed stimulation and interferon-gamma secretion upon all stimuli tested. Moreover, S-adenosil-L-methionine counteracted chenodeoxycholic acid-mediated inhibition of lymphocyte proliferation and interleukin 2 secretion. The results of our study confirm the immunosuppressive role of chenodeoxycholic acid on both secretive and proliferative lymphocyte functions and provide evidence of immunomodulatory activities of S-adenosil-L-methionine and its capacity to antagonize chenodeoxycholic acid-mediated inhibition of lymphocyte proliferation and interleukin 2 secretion.

Antibodies, Monoclonal↗
PubMed1997

Plicometer skin test: a new technique for the evaluation of cutaneous involvement in systemic sclerosis.

This study tries to establish a new method for the evaluation of skin lesion extension and progression in systemic sclerosis (SSc) patients. Plica thickness measurements of 200 healthy subjects and 19 SSc patients by plicometer were performed, and an arbitrary plicometer skin score was created. The plicometer skin score was compared to m-Rodnan's score on the same patients. The statistical association between the plicometer score and DLCO values in SSc patients was analysed. Plicometer plica thickness cut-off values of normality were established for nine skin areas. High specificity (95-99%) and a high negative predictive value (95.5-100%) were found. The sensitivity and the positive predictive value were 52.6-100% and 52.4-90.5%, respectively. The coefficient of variation of the plicometer score (0.05-0.14) was lower than that of the m-Rodnan score (0.22-0.33). A statistically significant association was found between skin score and DLCO. The study underlines the accuracy and reproducibility of the plicometer skin test, and suggests its utility in monitoring scleroderma progression.

Adolescent↗
PubMed1997

Role of interleukin (IL)-2 and IL-15 in the tumour progression of a melanoma cell line MELP, derived from an IL-2 progressor patient.

MELP is an interleukin (IL)-2 receptor (IL-2R; alpha+ beta+ gamma-) melanoma cell line that was derived, before the beginning of the immunotherapy, from a patient whose metastasis increased in size during treatment with IL-2/interferon-alpha. In these cells, continuous culture in the presence IL-2 (1000 UI/ml) causes the selection of a cell sub-line (termed MILG) expressing the gamma-chain which is tumorigenic in nude mice. Here, we further analysed the characteristics of MELP and MILG cells as well as clones selected at limiting dilution in the presence of high concentrations of IL-2 or IL-15, or those selected after transfection for the expression of a human IL-2 transgene (MELP-CL1). MELP cells, but not six other melanomas cell lines, shed two soluble immunosuppressive molecules, CD25 and intercellular adhesion molecule-1, whose levels also strongly increase in vivo during immunotherapy. In vitro MELP cells express transcripts for IL-6, transforming growth factor, basic fibroblast growth factor and vascular-endothelial growth factor. Cloning at limiting dilution was obtained in culture fed with IL-2 or IL-15. All these clones, as MILG cells, express the transcript for the IL-2R gamma chain. This could favour improved interactions with cytokines using this chain. By contrast, MELP-CL1 cells, which secrete low amounts of biologically active IL-2 (200 UI/10(6) cells) exhibit a phenotype and growth characteristics similar to those of the parental MELP cells. Indeed, a crosslinking experiment with 125I-IL-2, has showed that MELP and MELP-CL1 cells display a scant IL-2 binding ability that is strongly increased in MELP cells fed for 1 week with 1000 UI/ml IL-2. These cells, as well as MILG cells express a betagamma-complex which can also bind IL-15. IL-2 induces a rapid tyrosine phoshorylation in MILG cells, which is followed by a prolonged induction of c-fos and c-jun genes. By contrast, in MELP cells IL-2 only causes a delayed induction of c-myc gene. All MELP derivatives, but not MILG cells, express the transcripts for IL-15, which is not secreted but is present as an intracellular protein. All MELP cells express the transcript for the IL-15R alpha chain. MELP-CL1 cells are not tumorigenic in nude mice, whereas MILG cells form rapidly growing tumours in 75% of the mice. Coinjection at the same site of MILG and MELP-CL1 cells causes the rapid regression of MILG tumours in 80% of the mice, whereas their bilateral injection causes the rapid development of MILG tumours in 100% of the nude mice. Finally, treatment in nude mice of MILG cells with low amounts of IL-2 (1000 UI per mouse) and IL-15 (50 ng per mouse) induces the development of much more aggressive tumours.The expression of functional IL-2Rs in a subset of human melanomas could be responsible for tumour progression.

Adult↗
PubMed1996

Human CD4-internal antigen anti-idiotypic monoclonal antibody: induction of a CD4-specific response in humans.

We previously showed that anti-idiotypic mAb (mAb2) F16-16D7 (16D7) to the paratope (or paratope-related idiotope) of the anti-CD4 mAb HP2/6 induces anti-CD4 Abs in BALB/c mice. In view of the potential ability of 16D7 to induce anti-CD4 Ab in humans and the potential benefits of anti-CD4 Abs in the treatment of autoimmune diseases, we evaluated the immunologic response to and assessed the safety of four 2-mg 16D7 s.c. injections in one patient with systemic lupus erythematosus (SLE) and one with rheumatoid arthritis (RA). 16D7 induced anti-isotypic and anti-anti-idiotypic Abs (Ab3), which were almost exclusively of the IgG isotype. Ab3 specifically reacted with 16D7 as they inhibited its binding to mAb HP2/6. Although Ab3 did not react with cellular or recombinant CD4 (rCD4), single-cell enzyme-linked immunospot assays of anti-CD4 Ab production revealed many more spot-forming cells in rCD4- and 16D7-coated wells than in wells coated with BSA or 16D7 isotype-matched MK2-23. Spot-forming anti-CD4 Abs were specifically induced by 16D7, since rCD4-dependent spot formation 1) was not observed with PBL from one patient with SLE, one with mixed connective tissue disease, and one with melanoma immunized with MK2-23; and 2) was inhibited by 16D7 and not by MK2-23. Spot-forming anti-CD4 Abs recognize a CD4 epitope identical (or closely related) to that seen by HP2/6, since this specifically inhibited spot formation. A substantial, although transient, CD4+ T cell depletion was only observed in the RA patient. Local and/or general toxicity and laboratory and/or clinical signs indicative of immunodepression or diseases relapse were not observed during an 18-month follow-up.

Adult↗
PubMed1996

IL2 triggers a tumor progression process in a melanoma cell line MELP derived from a patient whose metastasis increased in size during IL2/INFalpha biotherapy.

Human melanomas may express both in vivo and in vitro functional IL-Rs and may be expected to directly respond to injected IL2. This may generate biological situations which may be favourable for the patient, but also for tumor progression. Here, we analyse the latter hypothesis. MELP is a melanoma cell line derived from a patient whose metastasis increased in size during IL2/IFN alpha biotherapy [correction of biotheraphy]. These cells have been characterized in vitro for their phenotype and for their sensitivity to IL2. In vitro MELP cells express an IL2-R alpha(+) beta(+) gamma(-) phenotype and IL2 treatment induces the acquisition of new functional characteristics represented (i) by the increased surface expression of two markers of metastatic evolution (ICAM-1 and CD44); (ii) by the stable induction of the IL2-R gamma with the appearance of functional IL2-R beta complex, which are also recognized by GM-CSF; (iii) by the inhibition of transcription of a regulatory cytokine such as IL6; (iv) by a differential effect of IL6 on CD44 surface expression in MELP cells treated or not with IL2 (MILG cells); (v) by the acquisition of faster growth rates and appearance of piling up and multilayer cellular organization; (vi) by the development of rapidly growing tumors in nude mice. IL2 induces in MELP cells a tumor progression process that could mimic the metastatic evolution observed in vivo during biotherapy. Therefore, MELP phenotype may help to define a subset of patients in which IL2 therapy may trigger unfavourable evolution.

Adult↗
PubMed1996

MEL-P, a GM-CSF-producing human melanoma cell line.

A human melanoma cell line, MEL-P, expressing granulocyte-macrophage colony-stimulating factor (GM-CSF) and its specific receptor was newly established from a primary nodular lesion of a patient with a particularly unfavourable prognosis. Cytogenetic, immunophenotypic, cytokine and intercellular adhesion molecule (ICAM)-1 production analyses confirmed that this cell line was similar to the fresh melanoma cells from which it had been established. MEL-P constitutes a valuable model for the study of multistep tumour progression and the role of biologically active GM-CSF production in human malignant melanoma. Our results show a decreasing expression of HLA class I molecules during in vitro culture, when GM-CSF secretion attains the highest levels, and a constantly high production of ICAM-1. The inhibitory effect of GM-CSF antisense treatment on cellular growth might suggest the presence of an autocrine mechanism. On the whole, these data are consistent with the possible involvement of high GM-CSF production in the metastatic competence of melanoma cells through the autocrine mechanism of growth and/or the activation of other migration-related molecules by its local production in metastatic invasion.

Adult↗
PubMed1996

Prednisone increases apoptosis in in vitro activated human peripheral blood T lymphocytes.

Glucocorticoid hormones (GCH) regulate, through the apoptotic process, the negative selection of immature T cells in the thymus. Because apoptosis seems to occur also in the maintenance of peripheral tolerance, we have investigated whether GCH may induce apoptosis in human mature lymphocytes. Peripheral blood lymphocytes (PBL) or peripheral CD4(+) and CD8(+) T cell subsets were cultured in the presence of phytohaemaglutinin (PHA) or PHA and prednisone (PDN) at 10(-3)-10(-12)M concentrations for 72, 96 and 120h. Cell cycle and membrane antigen expression were evaluated by flow cytometry and DNA degradation was detected by agarose gel electrophoresis. PDN blocks PBL growth in the G1 phase of cell cycle and inhibits both IL-2 receptor (IL-2R) expression and IL-2 secretion. Apoptosis is clearly increased by PDN in PHA-activated human PBL, and the apoptotic effect of PDN is stronger on CD8(+) than on CD4(+) T lymphocytes. All these effects are dose- and time-dependent. The addition of exogenous IL-2 did not rescue lymphocytes from PDN-increased apoptosis. These results show that PDN increases apoptosis in mature activated human peripheral blood lymphocytes, suggesting a possible role of GCH in the maintenance of immune tolerance at post-thymic level.

Adult↗
PubMed1996

Catecholamine content and in vitro catecholamine synthesis in peripheral human lymphocytes.

We studied the catecholamine (CA) content in peripheral human lymphocytes and the ability of these cells to synthesize CA in vitro. CA were separated by high performance liquid chromatography (HPLC) and determined in the supernatant by electrochemical detection as well as being determined after ultrasonic cell disruption in mononuclear leukocytes, adherent cells (monocytes/macrophages), total lymphocytes, and B- and T-cell enriched fractions. T lymphocytes contained L-Dopa and norepinephrine (NE), whereas B lymphocytes contained only L-Dopa. Lymphocytes seem to be able to synthesize NE from both L-tyrosine and L-Dopa added to the incubation medium in concentrations similar to the peripheral venous plasma (i.e. 5 x 10(-5) m and 10(-8) m, respectively). The addition of D-Dopa did not increase intracellular NE. alpha-methyl-p-L-tyrosine, benserazide, disulfiram, and fusaric acid (which are inhibitors of the enzymatic pathway) all decreased the synthesis of NE. After the addition of [3H]-L-Dopa (10(-8) m and 10(-7) m) to the incubation medium, [3H]-NE and [3H]-dopamine appeared. By increasing the concentration of L-Dopa in the medium (< 10(-6) m), CA were detected in the supernatant as well. These data show that peripheral human T lymphocytes contain and are able to synthesize CA from normal precursors in physiologic concentrations, i.e. a CA synthetic pathway is shown in nonneural cells. These data seem to support the hypothesis of autocrine and paracrine loops in the regulation of lymphocyte activity in lymphocytes taken from human cerebrospinal fluid (as suggested by other authors).

Adult↗
PubMed1996

Serum HLA class I antigen levels in allogeneic bone marrow transplantation: a possible marker of acute GVHD.

The levels of serum HLA class I antigens were determined at weekly intervals up to 5 weeks in 46 patients who had undergone allogeneic BMT. In patients with GVHD grade I or with GVHD grade I and fever of unknown origin (FUO), serum HLA class I antigen levels did not change during the observation period. In patients with GVHD grade II-IV serum HLA class I antigen level significantly increased in the week before the onset of GVHD, was maximal at the onset of GVHD and then persisted unchanged in the following 2 weeks. In patients with GVHD grade I or GVHD grade II-IV and infections whose onset coincided with that of acute GVHD a significant increase of serum HLA class I antigen level was found 2 weeks after the onset of the infectious episode. An increase of serum HLA class I antigen level was also found before the onset of repetitive GVHD grade II-IV episodes as well as during and after infectious episodes whose onset occurred after the onset of acute GVHD. The mean +/- s.d. concentrations of serum HLA class I antigens during GVHD grade II-IV episodes (9.4 +/- 3.4 micrograms/ml) and 2 weeks after the onset of infectious episodes (7.1 +/- 1.6 micrograms/ml) are significantly (P < 0.01 and P < 0.05, respectively) higher than that found 2 weeks before the onset of GVHD (3.0 +/- 0.5 micrograms/ml). The results of the present investigation suggest that measurement of serum HLA class I antigen level may be a possible marker to detect an acute GVHD following BMT.

Acute Disease↗
PubMed1996

[The immunological activity of corticosteroids].

Corticosteroids are among the most used anti-inflammatory and immunosuppressive drugs. The most recent reports have shown that the corticosteroids: A) modulate the lymphocyte recirculation and induce a lymphocyte depletion mainly regarding to the CD4 cells. B) Inhibit several lymphocyte activities, as well as their capacity to secrete cytokines and their clonal expansion under activating conditions. C) Induce apoptosis in primed T cells. D) Modulate the synthesis and activity of nuclear factors AP1 and NFkB. Moreover several data suggest that the molecular manipulations of cortisol, performed with the aim of improving its therapeutic efficiency, might change its capacity to bind the cytoplasmic receptor and/or generate CTS/CTS-R compounds that have different capacity to migrate through the nuclear membrane and/or to activate the nuclear responsive elements inducing different biologic responses.

Adrenal Cortex Hormones↗
PubMed1995

CD4+ Th0 cell clones, isolated from a metastatic lymph node of a melanoma patient, possess cytolytic function.

In the present study T lymphocytes isolated from a metastatic lymph node (T-LNL) of a melanoma patient have been cloned. In the attempt to verify whether T-LNL may acquire in vitro functional activities in the absence of tumour-associated antigens, they were cloned utilizing allogenic lymphocytes as feeder cells. Nineteen clones generated from T-LNL proved to be CD4+ and, among these, five were able to kill autologous and allogeneic human melanoma cells in HLA-class-II-restricted way. On the basis of their cytokine production, these CD4+ cytolytic T-LNL clones were shown to belong to the Th0 subset and three of them expressed the V beta 17 chain of the T cell receptor. These results suggest the presence of melanoma-specific but functionally inactive lymphocytes with T cell receptor oligoclonality in the lymph node environment. These specific T cells may acquire in vitro the capacity to kill autologous and allogeneic tumours without any induction by autologous melanoma cells.

CD4-Positive T-Lymphocytes↗
PubMed1995

Behavior of soluble HLA class I antigens in patients with chronic hepatitis C during interferon therapy: an early predictor marker of response?

Soluble HLA class I antigens (sHLA-I), beta 2-microglobulin (beta 2-mu) and alanine aminotransferase (ALT) serum levels have been evaluated in 16 patients affected by chronic hepatitis C treated for six months with recombinant interferon-alpha (rIFN-alpha, 3 MU three times a week). The predictor role of sHLA-I and ALT modifications with respect to the response to rIFN-alpha therapy was also evaluated. Six patients responded (group 1), five patients relapsed followed in initial responses (group 2), and five did not respond to rIFN-alpha treatment (group 3). The baseline serum levels of sHLA-I and beta 2-mu were significantly higher in all three groups of HCV-positive patients with respect to HCV-negative controls (P < 0.05). A significant increase of sHLA-I serum level with respect to baseline value (P < 0.001) was observed in group 1 patients after two weeks of rIFN-alpha treatment. sHLA-I serum level then decreased, although remaining steadily and significantly increased with respect to baseline (P values ranging from 0.05 to 0.01) in the following five months and then returned to baseline one month after the end of rIFN-alpha administration. No significant variations of beta 2-mu serum levels were detected throughout the observation period. In group 1 patients ALT serum levels significantly decreased after two weeks of rIFN-alpha treatment (P < 0.001) and then remained in the normal range throughout the observation period. In the other two groups of patients no relevant variations of sHLA-I and beta 2-mu serum levels were found during and after rIFN-alpha therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Interferons up-regulate with different potency HLA class I antigen expression in M14 human melanoma cell line. Possible interaction with glucocorticoid hormones.

The relative potency of interferon alpha (IFN alpha), interferon beta (IFN beta), and interferon gamma (IFN gamma) in inducing the expression of HLA class I antigens, as well as their capacity to counteract the inhibition induced by glucocorticoid hormones on HLA class I antigen expression, were analysed in the human melanoma cell line M14, both at membrane and at mRNA level. The data obtained indicate that (a) IFN enhance with different potency (IFN gamma > IFN beta > IFN alpha) the expression of HLA class I antigens in M14 cells, (b) prednisone inhibits HLA class I antigen expression, (c) glucocorticoid hormones, when associated with IFN alpha or IFN gamma, inhibit the HLA class I enhancement induced by IFN alone, and, finally, (c) the association between 1 microM prednisone or 1 microM deflazacort and IFN beta seems to potentiate the enhancing capacity of IFN on the expression of HLA class I molecules at the mRNA level. These findings, if confirmed, might indicate that IFN and glucocorticoid hormones are not mutually exclusive in the management of human melanoma.

Drug Synergism↗