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Biomedical subjects

E Leonardo

Publications and source records attributed to E Leonardo.

At least 37 records · Page 2Linked to original sources

Putative prethymic T cell precursors within the early human embryonic liver: a molecular and functional analysis.

Hematopoietic cells present in the liver in early human fetal life were characterized by phenotypic analysis using a broad panel of monoclonal antibodies. Expression of very late antigen 4 and leukocyte function-associated antigen 3 cell adhesion receptors and 4F2 cell activation molecules was found in all fetal liver hematopoietic cells before acquisition of T cell-, B cell-, or myeloid-specific surface markers, and before the time of intrathymic colonization. Molecular studies showed that expression of the interleukin 2 receptor beta (IL-2R beta) also occurred in the embryonic liver at this early ontogenic stage. In contrast, no expression of IL-2R alpha or IL-2 transcripts was found in fetal liver cells, whereas transcription of the IL-4 gene was detected in a small fetal liver cell subset. Putative T cell precursors were identified among the hematopoietic fetal liver cells by the expression of genes encoding the gamma, delta, epsilon, and zeta invariant chains of the CD3-T cell receptor (TCR) complex. However, no transcription of the polymorphic alpha and beta TCR genes was detected. Functional in vitro assays further demonstrated that fetal liver hematopoietic cells from those early embryos were capable of proliferating in response to T cell growth factors, including IL-4 and IL-2. However, whereas IL-4-induced proliferation paralleled the appearance in vitro of CD45+CD7-CD4dull cells expressing the CD14 myeloid antigen, as well as of CD34+ primitive hematopoietic progenitors, differentiation into CD45+CD7+CD8+CD3- immature T cells was observed when using IL-2. Moreover, coculture with thymic epithelial cell monolayers provided additional evidence that early fetal liver hematopoietic cells may include very primitive T cell precursors, which were able to differentiate in vitro into TCR alpha/beta+ mature T cells. Therefore, our results indicate that, after triggering of the T cell-specific maturation program in primitive fetal liver hematopoietic progenitors, specific signals provided intrathymically by epithelial cells may fulfill the requirements to drive terminal differentiation of prethymically committed T cell precursors.

Antigens, CD↗

Prognostic significance of Ki67 labelling in resected non small cell lung cancer.

One hundred and eleven tissue samples of primary non small cell lung cancer obtained from patients undergoing radical surgery for resectable disease were investigated for the presence and distribution of Ki67 related antigen using an immunohistochemical technique, as a marker of the proliferative activity of the tumour. No correlation was seen between Ki67 expression and clinico-pathological variables (sex, age, histology, grading and pTNM stage) but disease-free survival was significantly lower in patients with higher Ki67 score (> 25% positive cells) at diagnosis (P < 0.03). Growth fraction evaluated by Ki67 labelling may provide a complementary prognostic parameter in non small cell lung cancer.

Adult↗

Rebound thymic hyperplasia following high dose chemotherapy and allogeneic BMT.

We describe a child with acute lymphoblastic leukemia who showed mediastinal widening 8 months after allogeneic BMT. Total thymectomy was carried out by the transcervical approach. Histologic examination showed only thymic hyperplasia. The immunohistologic investigation revealed a normal distribution of thymic cell elements, without evidence of clonal proliferation of lymphocytic subpopulations. This case supports the hypothesis that thymic hyperplasia following chemotherapy may be merely a rebound phenomenon. The patient had an uneventful postoperative recovery and remains in remission more than 1 year after BMT.

Antigens, Differentiation, T-Lymphocyte↗

Attenuation of autoimmune disease and lymphocyte accumulation in MRL/lpr mice by treatment with anti-V beta 8 antibodies.

MRL-MP-lpr/lpr mice are afflicted by a severe systemic autoimmune disease that is aggravated by the lpr mutation resulting in the accumulation of phenotypically abnormal lpr cells (CD3+CD4-CD8-) in all lymphoid issues including hyperplastic lymph nodes. Given that products of the T cell receptor V beta 8 gene family are overrepresented among lpr cells, different schedules aimed at selectively decreasing the frequency of lpr cells were designed. First, continuous administration of the monoclonal antibody F23.1 (specific for V beta 8 products) resulted in a significant depletion of V beta 8+ cells and prevented the manifestation of lymph accumulation at the same time as it reduced the serological, clinical, and histopathological signs of autoimmune disease. Along the same line, administration of either F23.1 or two different anti-F23.1 anti-idiotypic antibodies to MRL/Mp-lpr/lpr mothers elicited, in the offspring, the production of antibodies sharing a recurrent idiotype with F23.1 and resulted in long-term amelioration of autoimmunity and lymphadenopathy. Thus, a strategy aimed at specifically reducing the frequency of a subset of lpr cells proved successful in mitigating the autoimmune process.

Animals↗

Monoclonal antibody Ki-67 in the study of the proliferative activity of bladder carcinoma.

We studied the proliferative activity of bladder carcinoma using monoclonal antibody Ki-67, which is able to stain a nuclear antigen exclusively present in cells in the cell cycle, that is with activated deoxyribonucleic acid (DNA). We used this immunohistochemical technique on neoplastic tissue removed by transurethral resection from 101 patients. A significant correlation was observed (p less than 0.003) between cells with activated DNA and histological grading, even though within the context of each grade we observed tumors with a different proliferation index. Furthermore, we studied the location of the activated cells in the context of the tumor. In invasive tumors (stages T1 to T4) cells with activated DNA were always present at the base of implant of the tumor and in the neoplastic tissue that infiltrates the bladder wall. In regard to noninvasive tumors (stage Ta), in 57% of the cases most cells with activated DNA were present in the vegetative portion of the tumor and there were no recurrences at followup, while in 43% of the cases such cells were present also or especially at the base of implant of the tumor, near the lamina propria. In the latter patients we observed a 94% recurrence rate. These results suggest that the immunohistochemical assessment of the proliferative activity of transitional tumors of the bladder, using monoclonal antibody Ki-67, and the evaluation of the location of stained neoplastic cells provide a more reliable estimate of biological aggressiveness than that obtained with histopathological patterns alone.

Antibodies, Monoclonal↗

[Alveolar macrophage subpopulations and circulating monocytes. Immunophenotypic study in healthy non-smokers].

Peripheral blood monocytes of 10 non-smoker normal subjects and the macrophages of their bronchoalveolar lavage fluid (BAL) were investigated with two commercially available monoclonal antibodies (MAC 387, CD14). Surface membrane monocyte cells show simultaneously both markers. Instead alveolar macrophage (MA) can be divided in three different phenotype groups by the expression of the two markers (MAC 387+/CD14-, MAC 387+/CD14+, MAC 387-/CD14+). Particularly, MA with MAC 387+/CD14+ phenotype are adherent cells and morphologically lack anthracosis. Their alveolar presence in non-smokers can be due to normal turnover of monocytes from blood into alveoli. By contrast MA with MAC 387+/CD14- phenotype are non-adherent cells without anthracosis. At last MA with MAC 387-/CD14+ phenotype are non-adherent cells but different amounts of anthracosis in their cytoplasm can be observed.

Adult↗

Identity of PB76 differentiation antigen and lymphocyte alkaline phosphatase.

Alkaline phosphatases (APases, EC 3.1.3.1) are ecto-enzymes bound to cell membranes by a phosphatidyl-inositol anchor. We have previously shown that APase is present on activated murine B cells and its expression correlates with the process of B cell differentiation into immunoglobulin secretion. Recently, a monoclonal antibody (mAb), G-5-2, that recognizes a 76-kDa molecule preferentially expressed on the surface of pre-B and plasma cells (PB76) was described. Some features shared by APase and PB76 differentiation antigen suggest that the G-5-2 mAb might be specific for lymphocyte APase. Here, we have analyzed this possibility and found an absolute correlation between PB76 expression in cells and their APase activity. Although PB76 has been described as a B cell-restricted marker, PB76 is also expressed on some T cells, such as the YAC-1 T cell lymphoma, that are known to bear APase. Treatment of YAC-1 cells with phosphatidylinositol-specific phospholipase C resulted in a quantitatively correlated removal of both APase and PB76 antigens. Moreover, we demonstrate that PB76 antigen has APase activity using an enzyme-antigen immunoassay with the G-5-2 mAb. We conclude that PB76 and lymphocyte APase are one and the same antigen.

Alkaline Phosphatase↗

Analysis and characterization of the interleukin 2 receptor alpha and beta chain expression in CD4-CD8- cells.

The differential effects that the binding of interleukin 2 (IL-2) to its beta or alpha beta receptors might induce in two different CD4-CD8- T-cell lines were analysed. While LD1.T3b, a double-negative T cell derived from MRL/lpr mice, constitutively expressed high levels of the IL-2R beta chain, YAC-1, a Moloney sarcoma virus-transformed CD4-CD8- T cell, expressed (as an activated T cell) the beta and alpha chains. The presence of IL-2 in the culture medium was lethal for LD1.T3b cells, while it had no effect on the growth of YAC-1 cells. IL-2 increased the expression of the beta chain and, to a lesser extent, of the alpha chain in YAC-1 cells. In addition, other markers such as CD4 and CD5 were induced by IL-2 in this cell line.

CD4-Positive T-Lymphocytes↗

[Autoimmune aspects of a case of chronic interstitial cystitis].

Chronic interstitial cystitis is a disease characterized by clinical recurring cystitis with histopathological aspects of a chronic aspecific inflammation of the bladder. Etiopathogenesis is still unknown, even if autoimmunity has been hypothesized in some cases. In this paper we report an immunopathologic and immunohistochemical study on a case of chronic interstitial cystitis. The inappropriate immunologic behaviour of the lymphocyte populations, the inhibition of leukocytes migration with bladder extracts and the immunofluorescent findings of IgG and C3 deposits in the mucosa support the hypothesis of an autoimmune pathogenesis of the disease.

Adult↗

[Distribution and prognostic value of CEA and TPA in cancer of the lung].

Serum levels of carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA) were investigated in 53 lung cancer patients. The higher percentage of patients with serum CEA positivity was observed within the anaplastic lung cancer group. TPA serum positivity was found in similar percentage in all the examined groups. Relationship between serum CEA positivity and/or serum TPA positivity and survival were then carried out.

Antigens, Neoplasm↗

Utility of immunohistochemical techniques in identifying various differentiation stages of T and B cell lineage and the related neoplastic transformed cells.

The lymphoid tissue provides the most productive conditions to the application of immunohistochemical techniques. This tissue is composed of many B and T phenotypically different cell populations ranging from stem cells to completely differentiated lymphocytes which can be identified by using monoclonal antibodies. These techniques also are of great help in classifying the malignant lymphocyte counterparts and, thus, in defining diagnostic and prognostic characters of different lymphomas/leukaemias.

Antibodies, Monoclonal↗

[Prognostic value of serum and tissue CEA evaluation in lung cancer].

Serum concentration of carcinoembryonic antigen (CEA) was determined in 53 lung cancer patients before and 1 month after surgery. Relationships between serum CEA levels after and before surgery and survival were carried out. Furthermore, histological sections of the neoplastic surgical material were stained with anti human CEA antibody using an immunohistochemical method. The positivity of the neoplastic cells and of the macrophages were then analyzed and discussed.

Adenocarcinoma↗

[Immuno-oncologic monitoring of patients with bronchial carcinoma. IV. Aspects of the immunocompetence system].

Some aspects of the immunocompetent system are tested in 84 lung cancer patients at time of diagnosis and during the natural course of the disease. Results show no significant variations for many immunological tests during the course of the neoplasia. Significant alterations are observed in T-lymphocyte and macrophage evaluation. Moreover, some immunological data are related to lung cancer post-surgical survival.

Adenocarcinoma↗