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Biomedical subjects

P Musiani

Publications and source records attributed to P Musiani.

At least 91 records · Page 5Linked to original sources
PubMed1991

Rapid perinatal growth mimicking malignant transformation in a giant congenital melanocytic nevus.

Transformation to malignant melanoma in a giant congenital melanocytic nevus observed on the right limb of a 3,300-g newborn boy was strongly suggested by the histologic features of its ulcerated and papular areas: atypical melanocytes, irregular melanin distribution, many mitotic figures, "pagetoid" invasion of the dermis, and destruction of the rete ridges. Electron microscopy, too, showed that the atypical melanocytes had irregularly shaped and folded nuclei, one or more nucleoli, and a cytoplasm rich in organelles and polymorphous melanosomes. Investigation with a panel of monoclonal antibodies, on the other hand, revealed the antigen phenotype of a proliferative melanocytic lesion unaccompanied by the plain expression of antigens usually observed in malignant melanoma. In addition, the clinical picture during a 2-year follow-up has been free from signs of locoregional and systemic progression.

Antigens, Neoplasm↗
PubMed1991

Immune cells in periapical granuloma: morphological and immunohistochemical characterization.

Samples of periapical granulomas obtained from 12 patients were examined using light and electron microscopes and monoclonal antibodies. Monocytes/macrophages, lymphocytes, and plasma cells were nearly always the most abundant cell populations. Ultrastructural analysis showed close contacts between macrophages and cells of the lymphoid lineage, with the lymphoid cells frequently demonstrating blastic features. Immunohistochemical staining with the anti-interleukin 2 receptor antibody showed that the concentration of labeled cells was quite low. The vast majority were lymphocytes, though some mast cells were also labeled. Mast cells were chiefly located in perivascular areas and interleukin 2 receptor-positive mast cells were frequently associated with lymphoid cells. mast cells could be part of a negative feedback mechanism in the immune response. By releasing histamine, they would block the immune response and by absorbing interleukin 2 they would remove it as an immune system stimulant.

Antibodies, Monoclonal↗
PubMed1990

Intrathymic deficient expansion of T cell precursors in Down syndrome.

To correlate the intrinsic cellular immunodeficiency, which is a major cause of increased susceptibility to polytopic infections in Down syndrome (DS) patients, with the histologic abnormalities observed in the thymus of these patients, we have studied thymus fragments and thymocyte cell suspensions from 15 non-institutionalized DS subjects. Comparing to the control age-matched samples, a reduced thymic cortex and a distinct depletion of CD1-positive (+) cells was observed by immuno-histologic examination. The phenotypic analysis of unselected thymocytes showed a significant reduction of CD3+, CD1+, CD4+, and CD8+ cells. When the total thymocyte population was separated into 10 fractions, using a continuous Percoll density gradient, a difference in cell distribution was observed. DS thymuses are almost devoid of high-density thymocytes (fractions 6-9) while more than 75% of the cells were recovered in the lightest 3 fractions (Frs). In addition, these thymuses were characterized by a marked depletion of CD1+ cells and by a conspicuous reduction of CD3+ cells normally present in the high-density Frs. On the other hand, the lightest 3 Frs of DS subjects were enriched in low-density CD1+ cells. Although enriched in these cells, normally characterized by a high mitotic activity, Fr1 DS thymocytes showed a reduced spontaneous proliferative capacity. When the expression of T cell receptor alpha- and beta-subunits was studied, the percentages of cells stained with anti-alpha and anti-beta antisera were found to be reduced in DS unfractionated thymocytes. The reduced number of high-density CD1+ thymocytes associated with a reduced spontaneous proliferative activity of low-density CD1+ thymocytes suggests that in DS thymuses there is a deficient expansion of immature T cells, resulting in a reduction of the various thymocyte subpopulations, including the thymocyte pool which differentiates into functionally mature T cells expressing the alpha-beta T cell receptor.

Child, Preschool↗
PubMed1990

Interleukin-2 receptor expression in human mast cells and basophils.

Surgical human thymus, upper respiratory tract, lung and small and large bowel specimens were analyzed for the presence of interleukin 2 receptor (IL2-R)-positive cells. Histochemical (toluidine) and immunologic (anti-IL2-R monoclonal antibody) staining procedures revealed a distinct anti-IL2-R positivity in most of metachromatically staining cells. These positive cells were observed not only in tissues showing strong inflammatory reaction and mast cell hyperplasia, as in Crohn's disease, but also in those not histologically affected by pathologic conditions. This finding suggested that human mast cells, like T blast cells, express the p55 chain of IL2-R on their surface. To see whether IL2-R was being actively synthesized, a cell preparation rich in peripheral blood basophils (PBB), which are cells closely related to mast cells, was obtained. Ultrastructural analysis of PBB after indirect immunogold procedure revealed that the vast majority expressed the IL2-R. Moreover, the presence of intracellular reaction products in the cytoplasm of most membrane-positive PBB was indicative of active antigen synthesis. Furthermore, Northern blot analysis evidenced specific IL2-R mRNA in PBB, while its expression was augmented several times when PBB were cultured in the presence of stimulated T cell supernatant.

Animals↗
PubMed1990

Effect of sulfurous (thermal) water on T lymphocyte proliferative response.

We studied the effect of sulfurous water thermal therapy on the phenotype and the proliferative response of peripheral lymphoid cells from ten subjects affected by chronic upper respiratory disease and from six suffering from articular and periarticular disorders. Sulfurous water (S-H2O) therapy did not modify the phenotype and function of peripheral blood mononuclear cells (PBMC) nor did it modify systemic immunologic reactivity. A different result was obtained by analyzing the response to mitogens of peripheral blood mononuclear cells in cell cultures containing graduated amounts of S-H2O. These "in vitro" studies have shown an important dose-dependent inhibitory effect of S-H2O on mitogen induced T lymphocyte proliferation and on IL2 production. H2S present in S-H2O seems to be the primary component responsible for inhibition. Our results are consistent with a local immunosuppressive role of S-H2O, which may explain part of the observed therapeutic effect of inhalation therapy on upper respiratory allergic disorders.

Administration, Inhalation↗
PubMed1989

Effect of low doses of interleukin-2 injected perilymphatically and peritumorally in patients with advanced primary head and neck squamous cell carcinoma.

For 10 days, four patients with advanced squamous cell carcinoma of the head and neck received two daily injections of 100 units of natural IL-2, one around the tumor, the second near the tumor-draining lymph nodes. No side effects were observed. Histologic and ultrastructural examination of tumor and lymph nodes recovered at surgery showed that in many instances neoplastic cells were intermingled with numerous lymphocytes and eosinophils. Lymph nodes displayed hyperplasia of both cortical and paracortical areas and epithelioid venules infiltrated by lymphocytes and granulocytes. In a few cases, a decrease or disappearance of neoplastic lesions was also documented both clinically and histologically.

Aged↗
PubMed1989

The expression of functional IL-2 receptor on activated macrophages depends on the stimulus applied.

Human peripheral blood monocytes (Mo) synthesize prostaglandin E2 (PGE2) when activated with lipopolysaccharide (LPS). This production is strongly enhanced by the addition of supernatant from phytohaemagglutinin (PHA)-activated T cells. To evaluate the factor(s) responsible for this enhancement we studied the effect of several cytokines on the PGE2 metabolism. Recombinant interleukin-1 (IL-1) or recombinant IL-2 strongly enhanced PGE2 synthesis in LPS-stimulated Mo cultures, whereas recombinant interferon-gamma (IFN-gamma) partially inhibited its production. To see whether the effect of IL-2 on Mo was due to the presence of IL-2 receptor (IL-2R) on the cell surface, flow cytometric analysis and electron microscopy were used to investigate IL-2R expression in unstimulated and stimulated Mo. Stimulated, but not resting, Mo displayed the p55 IL-2R chain on their cellular surface and associated with the polyribosomes of the rough endoplasmic reticulum in the cytoplasm. This finding strongly suggested that the p55 chain of the IL-2R was synthesized by activated Mo. To confirm this result, 125I-labelled IL-2 was bound under high- and low-affinity conditions and cross-linked to Mo cultured in the presence of LPS, IFN-gamma or IL-1. The cross-linked 125I-IL-2/IL-2R complexes were analysed by SDS-PAGE. Mo cultured with LPS, IFN-gamma and IL-1 expressed the p55 protein detected by low-affinity cross-linking, whereas only LPS-stimulated Mo displayed a barely detectable band with an apparent MW of 70,000 under high-affinity binding conditions. In addition, stimulated Mo were found capable of producing the soluble form of IL-2R. Finally, LPS-activated Mo only responded to the addition of IL-2 by an increase in PGE2 production, suggesting that the function of IL-2R on activated Mo is linked to the stimulus applied.

Biological Factors↗
PubMed1989

The role of arachidonic acid metabolite PGE2 on T cell proliferative response.

We have examined the role of cyclooxygenase and lipooxygenase-derived metabolites of arachidonic acid (AA) during T cell activation. One of the major products of cyclooxygenase activity is prostaglandin E2 (PGE2). As is known, macrophages (Mo) are the main PGE2 producer cells among the peripheral blood mononuclear cells (PBL) and can be induced to release PGE2 during T cell activation. On culturing PBL with T cell mitogens such as phytohemagglutinin (PHA) or monoclonal antibody OKT3, the levels of PGE2 produced by Mo were positively correlated with the entity of the T cell mitogenic signal. During T cell activation, subcellular factors able to provide positive or negative signals on the Mo PGE2 production are released in culture. We observed that recombinant IL2 strongly enhanced PGE2 synthesis in lipopolysaccharide (LPS) stimulated Mo culture, while recombinant interferon gamma (IFN-gamma) partially inhibited its production. Moreover, purified IL1 induced PGE2 synthesis in resting Mo and increased its production when Mo were activated by LPS. The PGE2 released during T cell activation seems to have no effect on T cell mitogenesis, since the addition of cyclooxygenase inhibitors did not influence the proliferative response of mitogen stimulated T cells. However, the addition of PGE2 to OKT3 stimulated PBL at the beginning of the culture period inhibited the proliferative response in a dose-dependent manner. Its addition had no effect on PHA-stimulated PBL cultures. The PGE2-dependent inhibition of OKT3-induced T cell proliferation declined progressively from about 50-10% as the addition of PGE2 was delayed from 0 to 24 hr.(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Factors↗
PubMed1988

Alterations in thymocyte subpopulations in Down's syndrome (trisomy 21).

To correlate the histologically observed thymic abnormalities with the cellular immunodeficiency found in Down's syndrome (DS), thymus fragments and thymocyte suspensions from 14 noninstitutionalized DS subjects were studied. Histologic examination and immunohistologic studies using an anticluster of differentiation (CD) 1 monoclonal antibody showed a contracted cortex due to cortical thymocyte depletion. When DS unselected thymocytes were phenotyped, a significant reduction of CD3-, CD1-, CD4-, and CD8-positive cells was found as compared to controls. To evaluate if the deficient expression of these markers was due to the reduction of thymocyte subsets identifiable on the basis of their physical properties, we separated DS unselected thymocytes into 10 fractions by continuous Percoll density gradient centrifugation. DS thymuses were almost completely devoid of high density thymocytes. Since in normal thymus, these cells correspond to small CD1+, CD4+, CD8+, and 50% CD3+ cortical thymocytes, their absence may explain the unrestricted reduction of markers on DS unfractionated thymocytes. Furthermore DS thymuses appeared to be enriched in CD1+ first fraction (Fr1) low density thymocytes of the Percoll gradient. Fr1 CD1+ cells constitute the main spontaneously proliferating pool in normal human thymus. When the spontaneous proliferating activity of DS Fr1 was compared to that of the control, a significant reduction was observed. This reduction associated with the absence of high density thymocytes, with the reduction of cells expressing alpha- and beta-chains of the T cell receptor and in conclusion with the lymphocyte depletion, suggests that in DS thymuses there is a deficient expansion of immature T cells resulting in a reduction of the various thymocyte subpopulations, including the thymocyte pool able to differentiate into functionally mature T cells.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1987

Platelet-activating factor (PAF) receptor antagonists inhibit mitogen-induced human peripheral blood T-cell proliferation.

The addition of L-652,731 and L-653,150, two synthetic PAF-specific receptor antagonists, to 72 hour cultures of phytohemagglutinin (PHA)-stimulated human peripheral blood mononuclear leukocytes (PBML) caused a dose-dependent inhibition of (3H)-thymidine incorporation into T-cells (IC50: 25 microM and 3.2 microM, respectively). This inhibition was not reversed by exogenous interleukin (IL)-1 and IL-2. PAF receptor antagonists did not affect the expression of IL-2 receptors (TAC-antigen) on T-cells. Exogenous PAF which by itself had no significant effect on PHA-stimulated PBML proliferation, only partially reversed the inhibition of proliferation caused by PAF receptor antagonists. These results may suggest the involvement of endogenously produced PAF in the regulation of immune reactions.

Cells, Cultured↗
PubMed1987

Expression of T cell receptor-alpha and -beta subunits in human thymocytes. An immunocytologic study.

The expression of the T cell receptor (Ti)-alpha and -beta subunits in human thymocytes was studied with the use of two rabbit antisera directed at constant regions of human Ti-alpha- and Ti-beta-chains (H36 and H38, respectively). Immunoperoxidase techniques were employed to count by light and electron microscopy the cells, in the various thymocyte subsets, bearing Ti-alpha and Ti-beta subunits. Of the unfractionated thymocytes, 88% +/- 5 SD and 56% +/- 8 SD were labeled by H38 and H36, respectively. More than 90% of cells in cluster of differentiation (CD)-1+ (mainly cortical) and CD1-CD3+ (mainly medullary) subsets were stained with H38. When tested by H36, 51% +/- 6 SD of CD1+ and 81% +/- 8 SD of CD1-CD3+ thymocytes were positive. In the immature CD3-CD1- subpopulation, less than 3% of cells reacted with H36, whereas 15% +/- 3 SD were stained by H38. Flow cytometry revealed that CD1+ (mainly cortical) thymocytes expressed CD3 surface antigen in a percentage similar to that of CD1+ cells positive for Ti-alpha subunits. Indirect double labeling procedures with immunogold- and peroxidase-conjugated second antibodies demonstrated that almost all CD1+/Ti-alpha + cells expressed the surface CD3 antigen, whereas a large proportion of CD1+/Ti-beta + cells did not. These results indicate a sequential expression of Ti-beta and Ti-alpha subunits during intrathymic T cell differentiation. They also suggest that assembly and surface expression of the CD3-Ti complex are linked to the production of Ti-alpha-chains in addition to Ti-beta subunits. Last, the expression of Ti-alpha and Ti-beta subunits was studied in peanut agglutinin (PNA)+, CD1+ blasts representing the main, spontaneously proliferating intrathymic pool. The lack of Ti-alpha and Ti-beta subunits and the absence of surface CD3 antigen on most of these blasts suggest that immature T cells are compelled to proliferate in the thymus in a CD3-Ti complex independent manner.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1987

T cell surface markers expression by immature human thymocytes in in vitro culture: role of Ia+ accessory cells.

Previous studies have indicated that the human thymus is composed of several discrete compartments. Cortical thymocytes are reactive with the monoclonal antibody anti-T6, whereas most medullary cells, unreactive with anti-T6, stain brightly with anti-T3 antibody, which defines mature T cell populations. By using an indirect immune rosette method, we isolated the minor thymocyte population (1 to 2% of all thymocytes) lacking both T3 and T6 but expressing T11 antigens. These cells could be maintained in culture supplemented with recombinant IL 2 (Rec-IL 2) for several days. Under these conditions, T3-T6- cells were shown to undergo phenotypic changes. In the absence of thymic macrophage (Mo), T3+ and T8+ thymocytes appeared in culture, whereas the development of T4+ cells strictly required the presence of Mo. The expression of T4 antigen could be largely prevented by the addition of anti-HLA-DR antibody, further indicating that Ia+ accessory cells had the ability to promote in vitro development of T4+ thymocytes. In the presence of Mo, not only T4+ but also T8+ cells were obtained. Double fluorescence staining with anti-T8-FITC and anti-T4-biotin demonstrated that after 12 days of culture, T4 and T8 antigens were mutually exclusive. Furthermore, during the course of these studies, we observed that under the culture conditions utilized (e.g., presence or absence of Mo), T3-T6-thymocytes failed to express the T6 antigen. Thus, the in vitro development of T cells bearing a mature phenotype could be obtained in the absence of intermediate expression of cortical (T6+) thymocytes.

Animals↗
PubMed1987

Glucocorticoid receptors and corticosensitivity of human thymocytes at discrete stages of intrathymic differentiation.

Human thymus is composed of several discrete compartments. Stage III thymocytes, located mainly in the medulla, stain brightly with anti-T3 monoclonal antibody; stage II thymocytes, located in the cortex, are T3- but react with T6 antibodies. The earliest identifiable intrathymic cell (stage I) expresses the sheep erythrocyte glycoprotein T11 but not T6 or T3 antigens. Within the thymus a phenotypically heterogeneous pool of proliferating lymphoblasts is present. This capacity to proliferate without in vitro activation is mainly attributable to thymocytes unable to respond to mitogens and expressing the cortical T6 marker. Both T3+ and T3-T6- cells respond to mitogen. However, in order to exhibit maximal proliferative responses, T3+ but not T3-T6- thymocytes require the addition of exogenous IL 2. Thymocyte subsets at distinct stages of intrathymic differentiation were then analyzed for glucocorticoid (GC) receptor content by using a whole cell assay with 3H-triamcinolone acetonide as tracer. The least mature T3-T6- thymocyte subset contained the highest levels of GC receptors . T3+ thymocytes exhibited a receptor content higher than that found in T6+ cells and similar to that reported for peripheral blood lymphocytes. Apart from the number, the GC receptor sites in all thymocyte subsets were similar in their affinities, kinetic characteristics, specificity for steroids, and ability to undergo translocation from cytoplasm to nucleus, and they behave in all these respects like binding sites of GC receptors in lymphoid and other cells. Independently of both phenotype and GC receptor content, all in vivo activated thymocytes (i.e., spontaneously proliferating cells) were similarly sensitive to the steroid inhibitory action in vitro. Both in the presence and in the absence of exogenous IL 1 or IL 2, the PHA-induced mitogenesis of T3-T6- cells was less inhibited by GC than that of T3+ thymocytes. Exogenous IL 1 and IL 2 were equally effective in removing, although not completely, the GC inhibition on T3-T6- proliferative responses to PHA. Relative to T3+ cell mitogenesis, only exogenous IL 2 was able to antagonize the steroid inhibitory action. The capacity observed in vitro of GC to differentially affect the proliferative potential or the cell viability of thymocytes belonging to functionally distinct subsets suggests that these hormones could regulate the intrathymic maturative pathways. Finally, although at present the physiologic relevance of the highest expression of GC receptors in intrathymic precursor cells remains unclear, the receptor density may be considered a marker of differentiation for the T lymphoid lineage.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1986

Proliferation of phenotypically immature human thymocytes with and without interleukin 2 receptors.

Previous studies have indicated that the human thymus is composed of several discrete compartments. Cortical thymocytes are reactive with the monoclonal antibody anti-T6, whereas most medullary cells, unreactive with anti-T6, stain brightly with anti-T3, which defines mature T cell populations. Only a minor thymocyte population lacks both T3 and T6 but expresses T11 antigens. Within the thymus, several proliferating lymphoblasts are present. In addition a distinct subset shows the capacity to proliferate in response to mitogens. By continuous Percoll density gradient centrifugation, we have obtained a cell fraction comprising the vast majority of cells able to proliferate spontaneously or after PHA stimulation. By a panning procedure performed with anti-T3 and anti-T6 antibodies, three phenotypically distinct thymocyte subsets were separated from this fraction, and their functional capabilities were tested. The spontaneous proliferating activity was found to be mainly attributable to thymocytes unable to respond to mitogen, expressing the cortical T6 marker and lacking receptors for IL 2. T3-positive cells are able to respond to mitogen. However, these thymocytes are incapable of producing the adequate amount of IL 2 required to fully saturate their intrinsic proliferative capability. Surprisingly, the phenotypically least mature intrathymic T lymphocytes (T3 and T6 negative) respond to phytomitogen, at least in part, in an interleukin-dependent manner. It is noteworthy that a large proportion of these T3- and T6-negative thymocytes express IL 2 receptors and class II MHC antigens without in vitro activation. These novel findings have potential implications in the context of current models of differentiation pathways within the human thymus.

Antibodies, Monoclonal↗
PubMed1986

Inhibitory effect of cyclosporin A on the OKT3-induced peripheral blood lymphocyte proliferation.

In this paper we studied the effect of cyclosporin A (CyA) on interleukin 1 (IL-1) and interleukin 2 (IL-2) production and on IL-2 receptor expression by human peripheral blood lymphocytes induced to proliferate following OKT3 monoclonal antibody stimulation. CyA inhibited T-cell proliferation in a dose-dependent manner and its effect was inversely correlated with the entity of the mitogenic signal. The drug reduced not only IL-2 synthesis but also IL-1 production. CyA was also found to be able to inhibit the expression of IL-2 receptors on T cells. By supplementing with IL-1 and/or IL-2 the cultures carried out in the presence of CyA, it became evident that the inhibition of IL-2 production mainly depended on the CyA-induced reduction of IL-1 synthesis. Thus the IL-2 production by "resting" T cells had to be considered as an IL-1-dependent event. In addition it was found that the presence of IL-1 constituted a crucial requirement for the induction and the positive modulation of IL-2 receptor expression. Although IL-2 could play a role in facilitating the expression of IL-2 receptors, its effectiveness to do so depended on the presence of IL-1. In conclusion, CyA is to be considered not only as a potent immunodepressive drug but also as a valuable tool for the study of T-cell activation and proliferation.

Antibodies, Monoclonal↗
PubMed1986

Phenotypical characteristics and proliferative capabilities of thymocyte subsets in human thymoma.

The phenotypical and functional characteristics of the lymphoid component present in ten human thymomas have been analyzed. Thymomas were classified according to the predominant epithelial cell type present in the neoplastic gland. In thymomas of the cortical type a large proportion, clearly higher than that present in mixed thymomas, of T6-positive lymphocytes was present. This T6 subset did not proliferate to mitogen but contained almost all thymocytes able to spontaneously proliferate. Higher proportions of T3-positive cells were found in mixed types of thymomas than in cortical-type tumors. This T3+ subset responded to mitogen stimulation and constituted the more mature intrathymic pool. Surprisingly we identified in thymomas a further subset, lacking the cortical and medullary markers T6 and T3, capable of responding to mitogen. The occurrence of higher proliferative responses to phytohemagglutinin (PHA) in the unfractionated population of cells from mixed thymomas than in the cells of cortical thymomas was judged to be attributable to the relatively higher content of both T3-positive and T3, T6-negative thymocytes in the former. Unlike T6+ thymocytes, T3-T6- as well as T3+ cells were practically devoid of spontaneous proliferative capacity. The expansion of the intrathymic lymphoid component in human thymomas should then be considered to be attributable to the "spontaneous" proliferative capacity of the T6+ cell pool. In this respect, cortical thymomas not only contained more T6+ cells than the mixed type but also exhibited a higher lymphocyte/epithelial cell ratio and more frequent mitotic figures.

Cell Separation↗