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Biomedical subjects

A Vicari

Publications and source records attributed to A Vicari.

At least 37 records · Page 2Linked to original sources

Endogenous granulocyte-macrophage colony-stimulating factor is involved in IL-1- and IL-7-induced murine thymocyte proliferation.

We have reported previously that IL-1 induces murine thymocyte proliferation in the absence of artificial comitogens, provided that the cells are cultured at high densities. In the present study, we show that, in these conditions, TdR uptake in response to IL-1 is diminished significantly by anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) Abs. Indeed, a substantial production of this growth factor occurs when thymocytes are cultured in the presence of IL-1. Maximal GM-CSF levels are attained within 3 days of culture, and mRNA expression is detected after a 48-h stimulation. Both GM-CSF production and IL-1-induced thymocyte proliferation are decreased considerably by the depletion of I-A+ Mac-1+ accessory cells. Yet, addition of exogenous GM-CSF to accessory cell-depleted thymocytes does not restore the proliferative response to IL-1 alone, suggesting the implication of another accessory cell-derived mediator. Our data design IL-7 as the endogenous factor required in our culture system because: 1) GM-CSF can reverse the decrease in the proliferation after accessory cell depletion when IL-7 is provided together with IL-1, and 2) the proliferative response to IL-1 plus IL-7 is diminished as much by neutralization of GM-CSF by its specific Abs as by accessory cell removal (approximately 30%). Finally, the cells responding to IL-1 + IL-7 were identified as mature CD4-CD8-TCR+ thymocytes by the use of bromodeoxyuridine (BrdUrd), suggesting that the GM-CSF produced by thymic accessory cells in response to IL-1 participates in IL-7-dependent, intrathymic expansion of the CD4-CD8-TCR+ compartment.

Animals↗

Interleukin 7 induces preferential expansion of V beta 8.2+CD4-8- and V beta 8.2+CD4+8- murine thymocytes positively selected by class I molecules.

We analyzed the phenotype and V beta-T cell receptor (TCR) repertoire, together with interleukin 7 receptor (IL-7R) expression in unfractionated thymocytes stimulated in vitro with IL-7. This culture system results in a specific proliferation of mature thymocytes belonging to the CD3+CD4-, CD4+8-, and CD4-8+ subsets. IL-7 induced a preferential expansion of V beta 8.2+CD4-8- and V beta 8.2+CD4-8- thymocytes. This phenomenon is not observed in beta 2-microglobulin-deficient mice, showing that a fraction of CD4+8- thymocytes, enriched in V beta 8.2+ cells, is selected by class I molecules in normal mice, as are a large proportion of CD4-8- alpha beta TCR+ thymocytes. Our findings also establish that IL-7 plays a major role in the expansion of rare thymocyte subsets, which could exert important functions in inflammatory and immune responses.

Animals↗

MTS-32 monoclonal antibody defines CD4+8- thymocyte subsets that differ in their maturation level, lymphokine secretion, and selection patterns.

We have previously described MTS-32 as identifying an Ag on both thymic stromal cells and thymocytes. In contrast with CD4+8+ and CD4-8+ thymocytes, of which the vast majority are MTS-32+, a notable subset of CD4+8- thymocytes is MTS-32-. Here we show that with regard to heat-stable Ags, Qa-2, and CD69 expression CD4+8- MTS-32- thymocytes are phenotypically enriched in mature cells when compared with their MTS-32+ counterparts. Moreover, sorted CD4+8- MTS-32+ thymocytes are unable to respond to anti-CD3 cross-linking, whereas MTS-32- CD4+8- thymocytes respond to the same stimulus by producing IL-4, IL-5, IL-10, IFN-gamma, and trace amounts of IL-2. In addition, MTS-32- CD4+8- and CD4-8- TCR-alpha beta+ thymocytes differ in their TCR V beta repertoire on a Mls-1a selecting background. We therefore suggest that the MTS-32 ligand is involved in signals consecutive with TCR recognition in the thymus, i.e., selection, activation, and lymphokine production.

Animals↗

A novel CD45RA+CD4+ transient thymic subpopulation in MRL-lpr/lpr mice: its relation to non-proliferating CD4-CD8-CD45RA+ tumor cells.

MRL-lpr/lpr mice have hypertrophied lymph nodes comprising CD4-CD8- T cells. In addition, they contain CD4+CD8- T cells co-expressing the CD45RA marker. The correlation between these two subpopulations has been difficult to assess. We analyzed the expression of CD45RA (with the RA3-2C2 antibody) in various thymic and peripheral T cell subsets, using three-color immunofluorescence. We showed that in lpr mice (i) a transient CD4+CD8- thymic subset co-expresses CD45RA during the course of the disease, and (ii) thymic as well as peripheral CD4-CD8- and CD4+CD8- T cells brightly express CD45RA; furthermore (iii) in the lymph nodes, during lymphadenopathy, CD4+CD8-CD45RA+ T cells show a broad range of the CD4 fluorescence intensity, and (iv) the increase in MHC class II expression is restricted to CD45RA-T cells of the thymus and lymph nodes of lpr mice. Taken together, these data suggest that the CD4+CD8-CD45RA+ population might generate the CD4-CD8- tumor cells. In addition, using the bromodeoxyuridine labeling technique, we demonstrate that these cells are not the result of increased proliferation.

Animals↗

Fetal liver cell transplantation in various murine models.

Allogeneic fetal liver cell transplantation has been shown to be able to reconstitute lymphopoietic systems of mice when these systems are defective or destroyed. Lethally irradiated mice or mice with inherited severe combined immunodeficiency disease (SCID) were grafted with 14 days gestation allogeneic fetal liver cells, then subjected to a follow-up for the immune tolerance to the donor and the normal or subnormal immune reconstitution allowing prevention of diabetes in NOD mice or cure of leukemia in AKR mice and of immunodeficiency in SCID mice. Briefly, when normal CBA mice were lethally irradiated and then grafted with allogeneic fetal liver cells from Balb/c mice, a specific immune tolerance was induced to donor skin grafts. Unrelated skin grafts were rejected and a response to antigens was observed in these chimeras. However, despite the capacity to develop hyperacute rejection of skin allografts, following hyperimmunization, these chimeric mice did not produce anti-H2 cytotoxic antibodies. In SCID mice (CB17), the immune reconstitution occurred when mice were grafted with allogeneic (C57/B16) as well as with syngeneic fetal liver cells. Human cells were found in SCID mice following implantation of human fetal liver and thymus cells. When NOD mice were irradiated, then grafted with allogeneic fetal liver cells, a large part of donor cells were found in NOD recipients, correlating with a low incidence of diabetes. Leukemic AKR mice grafted with allogeneic fetal liver cells had virtually no leukemia relapse, suggesting a strong graft-versus-leukemia effect following such a transplant.

Animals↗

High heparin released platelet factor 4 in uncomplicated type 1 diabetes mellitus.

The role of platelet activation in diabetic microangiopathy is still controversial. We evaluated the degree of platelet activation in relation to vessel wall damage in three selected, well matched groups of subjects (10 healthy controls; 20 insulin dependent diabetic patients, 10 without microangiopathy and 10 with microangiopathy). We measured beta TG and PF4 plasma levels before and 5, 15 and 90 min after a heparin bolus i.v. (5000 U). beta TG basal levels were increased only in diabetic patients with microangiopathy. Diabetic patients without microangiopathy showed significantly higher levels of heparin released-PF4 (HR-PF4) in comparison with healthy controls. High levels of HR-PF4 seem to be an early marker of in vivo increased platelet activation in uncomplicated diabetes mellitus.

Adult↗

Signal requirements for activation of leukaemic T cells from a chronic lymphocytic leukaemia (T-CLL).

In order to define the signal requirements for leukaemic T cell activation, the proliferation and interleukin-2 (IL-2) production of peripheral lymphocytes from a patient with a HTLV-I-, CD4+, CD45RA+ CD45RO+ CD25- T-CLL were evaluated after the delivery of different stimuli. Unlike resting CD4+ normal T lymphocytes that can be activated only by a two-signal stimulation, T-CLL cells proliferated and released IL-2 in response to a pair of anti-CD2 monoclonal antibodies (MoAbs) or concanavalin A (Con A) in the absence of both accessory cells (AC) and phorbol myristate acetate (PMA). The two stimuli were also able to induce CD25 expression within 12-20 h on the majority of T-CLL cells. A response to anti-CD3 and anti-CD28 MoAbs was detected only in the presence of PMA, similar to that observed in normal resting T lymphocytes matched for phenotype. Both Con A- and CD2-induced proliferation were strongly inhibited by the addition of anti-CD25 MoAb. Furthermore, T-CLL lymphocytes acquired anti-tumour lytic activity after culture in the presence of PMA and ionomycin. We conclude that HTLV1- CD25- T-CLL can be characterized not only by morphological and phenotypical studies but also on the basis of signal requirements for cell activation.

Antibodies, Monoclonal↗

EDTA-dependent pseudothrombocytopaenia: a 12-month epidemiological study.

The phenomenon of in vitro platelet clumping and consequent pseudothrombocytopaenia in the presence of EDTA has been studied in 33,623 subjects referring to a general hospital in a 1-year period. The observed frequency was 0.13%. EDTA-dependent pseudothrombocytopaenia (PTP) was suspected when a routine blood counting by the Coulter S-Plus IV/D showed a peculiar leucocyte histogram and pseudoleucocytosis. Confirmation was obtained by the manual count and by the finding of platelet aggregates in a stained blood smear. EDTA-dependent PTP was diagnosed when the platelet number and the morphological examination of blood anticoagulated with sodium citrate from the same patient were normal. EDTA-dependent PTP was found in 23 subjects aged from 19 to 79 years (0.068% of the study population): 17 were patients suffering from miscellaneous diseases, while six were apparently healthy. As a rule, platelet clumping was evident within 60 minutes from blood collection, but a longer latency (2-3 h) was observed in a few cases. EDTA-dependent PTP is a rare, but misleading phenomenon, the recognition of which is important in order to avoid expensive and potentially harmful procedures.

Adult↗

Ultrastructural characteristics of idiopathic spermatidic arrest.

Previous studies on some cases of idiopathic spermatidic arrest showed an anomaly in glucose metabolism, in particular decreased utilization of glycogen at stage 3 of spermatogenesis, when condensation of the spermatid head commences. Histological patterns seen on light microscopy confirmed the reduced utilization of glycogen at stage 3 of spermatogenesis. Electron microscopy revealed an arrest at stage 3 of spermiogenesis and, at the cytoplasm level of the Sertoli cell, a modification in the smooth endoplasmic reticulum characterized by the presence of dilated cisternae. From a morphological viewpoint, the equivalent of a biochemical modification which characterizes this maturation disorder in the germinal epithelium is hypothesized.

Humans↗

Myosin-like microfilaments in the human normal and pathological testis.

The immunofluorescent staining of the human normal testis shows that both peritubular and tubular cells bind antimyosin-like antibodies. The same cells are provided with a large amount of microfilaments within the cytoplasm. The thin microfilaments observed by electron microscopy in various cells of the human testis likely correspond to the sites of immunofluorescent staining. In pathological specimens there can be observed a decrease in peritubular smooth muscle cells associated with a decrease in cytoplasmic microfilaments and in the immunofluorescent staining of some cells.

Cytoplasm↗

Single nightly administration of ketoprofen (Orudis) and indomethacin suppositories in the management of osteoarthritis: a double-blind trial.

In a double-blind trial carried out on 60 patients with osteoarthritis at various localizations, ketoprofen (Orudis), administered as a single nightly 100 mg suppository for ten days, was significantly more active and better tolerated than indomethacin, administered in the same way. Patient's and doctor's assessment was also in favour of Orudis. Laboratory examinations were not affected by either drug.

Clinical Trials as Topic↗

Effect of the antihistaminic agents meclastine and dexchlorpheniramine on the response of human growth hormone to arginine infusion and insulin hypoglycemia.

Histamine is found in most tissues including the central nervous system. Here it reaches the highest concentrations in the hypothalamus and in the median eminence. In order to evaluate the possible role of endogenous histamine in the control of human growth hormone (hGH) secretion, we investigated the effect of two anti-histamine drugs, meclastine and dexchlorpheniramine, on the hGH response to arginine infusion and to insulin hypoglycemia in 30 normal subjects. The oral administration of meclastine for three days or the intravenous infusion of dexchlorpheniramine significantly reduced the hGH response to arginine infusion. Neither drug affected the secretion of hGH following insulin hypoglycemia. These results suggest that histamine is involved in the control of hGH release, at least in response to arginine. Our data are consistent with the finding that histamine stimulates GH release in the baboon (Meyer and Knobil, Endocrinology 80: 163, 1967) and with previous results indicating that the release of hGH in response to different stimuli is subject to different regulatory mechanisms.

Adult↗

[Primary neuroendocrine carcinoma of the skin: histologic, immunohistochemical and ultrastructural study of a case with highly aggressive biological behavior].

We report a histological, immunohistochemical and ultrastructural study of a case of neuroendocrine carcinoma of the skin, which occurred in a 52 years old woman in the dermal, subcutis and soft tissues of the left buttock. Clinically this neoplasm, which was related to intramuscular injections and a to a following abscess, had rapidly reached unusual dimension compared with other cases of neuroendocrine carcinoma of the skin reported in the literature. The patient died three months after presentation with distant metastases. A variable percentage of the neoplastic cells was positive for low molecular weight cytokeratins (CK), neurofilaments (NF), neuron specific enolase (NSE) and occasionally for vaso-intestinal polypeptide (VIP). Ultrastructural investigations showed two types of neoplastic cells, identified for some features of the nucleus and of the cytoplasm; these two groups of cells are, in our opinion, related to different stages of cellular development. Our results, in agreement with some observations reported in the literature, give evidence of a possible origin of neuroendocrine carcinoma of the skin from an undifferentiated cell which is capable of neuroendocrine or ectodermal differentiation.

Abscess↗