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Biomedical subjects

G Lucivero

Publications and source records attributed to G Lucivero.

At least 19 recordsLinked to original sources

Direct or reverse correlations within the expression of activation, differentiation or T-B cooperation molecules on chronic lymphocytic leukemia B cells.

AIM: B-cell chronic lymphocytic leukemia (B-CLL) is characterized by homogeneous coexpression of CD19, CD23 and CD5, and poor expression of membrane Ig. The aim of this study was to evaluate, in B-CLL patients and in healthy subjects by flow cytometry, B cell expression of surface molecules involved in cell activation, differentiation, T-B cooperation and apoptosis. METHODS: The study population consisted of 29 patients (16 men and 13 women; mean age: 66.5 years) with B-CCL. The control group consisted of 16 sex- and age-matched healthy subjects. The results are reported as percentages and mean fluorescence intensity (MFI) of CD19+ cells coexpressing each analyzed molecule. RESULTS: We found that the lymphocyte activation markers, CD69, CD25 and CD11c, were more expressed in B-CLL patients than controls. CD38 and CD95 expressions were higher on normal B lymphocytes than leukemic B cells. Finally, CD80 and CD86, molecules involved in T-B cooperation, showed an inverse expression between lymphocytes of B-CLL patients and healthy subjects. CD80 was higher on normal than leukemic B cells, while CD86 expression was higher on CLL B cells. Linear regression analysis showed a positive correlation between CD80 and CD95 expression on leukemic B cells; a reverse correlation was observed between CD69 and CD11c. CONCLUSION: These results suggest that common mechanisms may regulate the simultaneous expression of CD80 and CD95 or the reverse expression of CD69 and CD11c, respectively, in different stages of B cell activation and/or differentiation.

Aged↗

[Late onset immunodeficiency with hypo-IgG and hyper-IgM, T CD4+ lymphocytopenia and vitiligo].

The Authors report the clinical case of a patient with a deficit of humoral immunity who developed infections since puberty. The serum levels of IgG and IgA decreased progressively in the fourth decade of life, while serum IgM increased. Moreover, the patient developed a marked CD4+ T lymphocytopenia and a meager B lymphocytopenia, vitiligo, positivity for anti-SSA/Ro autoantibodies and granulomatous phlogosis of the knee. The heterogeneity of the clinical and laboratory data suggests that this patient might present an overlap immunodeficiency syndrome with some of the clinical and immunological features typical of the hyper-IgM syndrome (in the X-linked or autosomal forms) and others that can be referred to a nosologically distinct humoral immunodeficiency such as the common variable immunodeficiency.

Adult↗

Lymphocyte subset reconstitution after HLA-identical placental blood transplantation (PBT) or PBT plus bone marrow transplantation (BMT) in three children with beta-thalassemia major.

The kinetics of circulating lymphoid cells were evaluated in three children suffering from beta-thalassemia major after HLA-identical sibling placental blood transplant (PBT) in one patient and placental blood plus bone marrow transplantation (BMT) in two patients. Recovery of the main lymphocyte subsets, as determined by phenotype analysis of circulating PBMCs, was complete within 2 months after transplant. NK (CD56+) cells were the first to appear in peripheral blood, followed by T (CD3+, CD2+, CD7+) and B (CD19+) cells. Of the T lymphocytes, the CD8+ were the first to reconstitute, but recovery of CD4+ cells was also rapid and within 6 months these T cells reached normal values. The expression of CD57 by NK or T cells was slightly delayed. The evaluation of RA and RO isoform expression of the CD45 molecule showed a prevalence of the CD45RA antigen with a ratio of 2-3:1. In the PBT only patient, T cells expressing the CD45RO antigen prevailed in the early post-transplant period. Severe or chronic GVHD was not observed. This experience demonstrates that reconstitution of lymphocyte subsets is successful in genetic hematological diseases after transplantation of HLA-identical placental blood or placental blood plus bone marrow from healthy or heterozygous siblings. Bone Marrow Transplantation (2000) 26, 743-747.

Blood Transfusion↗

A 'de novo' arisen case of angioedema C1-inhibitor deficiency dependent: possible mutagenic effect of azathioprine?

It is reported that a C1-inhibitor (CI-INH) deficiency dependent angiodema case arose 'de novo' in a child without a family history of this disease. His mother was undergoing immunosuppressive therapy (50 mg of azathioprine plus 8 mg of methyl-prednisolone daily) during pregnancy, uninterrupted for seven years because of a kidney transplant. All the other known causes of acquired C1-INH deficiency were excluded. An involvement of an azathioprine-induced C1-INH gene mutation is hypothised.

Angioedema↗

Functional characteristics of cord blood T lymphocytes after lectin and anti-CD3 stimulation. Differences in the way T cells express activation molecules and proliferate.

Newborns are more susceptible than adults to infections, which suggests a relative immaturity of the immune system early after birth. Cord blood T cells differ significantly both in surface phenotype and function from adult T cells. We examined the proliferation and expression of activation molecules by lymphocytes isolated from umbilical cord blood or peripheral blood of adults. The lymphocytes were cultured for 5 days in the presence of phytohemagglutinin, concanavalin A, or anti-CD3 monoclonal antibody. Cord blood T cells expressed the CD45RA molecule, while a low proportion expressed the RO isoform, a marker of primed or activated lymphocytes. Furthermore, more than 95% of neonatal lymphocytes bear the CD38 molecule, but do not express the CD57 molecule. After stimulation by phytohemagglutinin or concanavalin A, the lymphocytes from newborns were activated and proliferated as efficiently as adult T cells. Anti-CD3 did not cause neonatal lymphocytes to proliferate, but these cells expressed activation molecules, such as HLA-DR antigens and the receptor for interleukin-2 and transferrin. The relevance of these findings to tolerance induction in immature cord blood T cells is discussed.

Adult↗

Ascitic fluid-associated lymphocytes in patients with metastatic ovarian cancer. Analysis of lymphocyte subsets and of phenotypical changes induced by "in vitro".

Ascitic fluid and peripheral blood samples, from seven patients affected by peritoneal carcinomatosis secondary to ovarian tumors, were analyzed to examine the phenotypic properties of ascitic fluid-associated lymphocytes (AFAL) and then asses T-cell activities in the presence of different interleukins. The AFALs showed a relative enrichment of CD2+, CD3+, CD5+, CD4+ T cells compared to the peripheral blood samples, while the contrary was true for CD56+ and CD57+ cells. The same phenomenon was observed in both CD3+, CD56+ and CD2+, CD56+ cell populations. Fewer CD71+ and CD25+ cells were found in the ascitic fluid suspensions whilst the opposite was true for HLA-DR+ lymphocytes. The data obtained from the in vitro incubation of AFALs in the presence of IL-1 (or), IL-2, IL-4, IL-6 or IFN showed that IL-1, IL-2 and IFN- can induce a two-fold increase in the percentages of HLA-DR+ T lymphocytes. IL-6, IL-2 and IL-1 seemed to have a fairly modest effect on CD25. A better survival of CD56+ cells was found only in the presence of IL-4 and IL-6. Even though preliminary and based on a limited number of patients, our results would seem to invite caution in instituting intraperitoneal administration of one or more cytokines for the treatment of such lesions in humans.

Aged↗

In vitro neutralization of T-2 toxin toxicity by a monoclonal antibody.

A T-2 toxin specific monoclonal antibody, IgG1 K, with a low level of ELISA cross-reactivity to Acetyl T-2, HT-2, and iso T-2 toxins has been produced. The ability of this monoclonal antibody to neutralize the cytotoxicity of T-2 toxin in PHA stimulated cultures of human lymphocytes was determined by the MTT method. The complete neutralization of the toxic effect of 0.02 microM T-2 toxin was obtained with 0.03 microM of MoAb, whereas the 50% neutralizing dose (ND50) was observed at 0.009 microM of MoAb. Partial neutralization was observed with Acetyl T-2 toxin (ND50 = 0.038 microM) and HT-2 (ND50 = 0.94 microM). These results could represent a rational for clinical use of T-2 toxin specific monoclonal antibody in prophylaxis and therapy of T-2 toxemia.

Animals↗

Monoclonal expansion of immunoglobulin not-secreting CD5+ CD11c+ CD38+ B-cells in a rare case of chronic lymphoplasmacytoid leukaemia.

We present the clinical and immunological features of a rare case of chronic lymphoid leukaemia with lymphoplasmacytoid morphology. The patient was first admitted suffering from weakness, pallor, dyspnoea, marked splenomegaly, hepatomegaly and systemic lymphadenopathy and panhypogammaglobulinaemia. White blood cell count revealed important leukocytosis (220 x 10(9) WBC/l) with 2% neutrophils and 98% lymphoid cells showing lymphoplasmacytoid features, while lymphoid cells of identical morphology severely infiltrated the bone marrow and lymph nodes. The disease, initially controlled by non aggressive chemotherapy over a period of 30 months, later evolved to a clinical and haematological picture suggestive of Richter's syndrome. Immunophenotyping of the leukaemic cells demonstrated a monoclonal expansion of B-cells bearing surface markers of typical CLL (CD5, CD19, CD20, CD21, CD22, CD23, CD24, CD40 and low density IgM+IgD/kappa) and also the CD11c and CD38 antigens. A proportion of these cells expressed activation markers (CD25, CD69 and CD71). Following in vitro activation with TPA or PWM, the cells responded by weak incorporation of 3H-TdR but failed to secrete immunoglobulins. These findings confirm the broad morphological, phenotypical and clinical spectrum of chronic lymphoid leukaemias.

Antibodies, Monoclonal↗

Immunomodulatory effects of fusarochromanones TDP-1 and TDP-2.

An in vitro peripheral lymphocyte blastogenesis system was used to investigate the biological activities of the fungal toxin fusarochromanone (TDP-1) and its monoacetyl derivative TDP-2. Briefly, cultures of human or bovine peripheral lymphocytes were exposed to TDP-1 or TDP-2 and a mitogen (PHA, Con A or PWM). After a standard incubation time, cell proliferation was quantified using the MTT bioassay. Human and bovine lymphocyte proliferation was inhibited by high concentrations of TDP-1; however, bovine lymphocyte proliferation was significantly increased at low concentrations of TDP-1. TDP-2 has similar but less pronounced effects on lymphocyte proliferation.

Amino Acids↗

In search of predictive markers of remission from insulin dependence in type 1 diabetes: a preliminary report.

We studied 18 newly diagnosed diabetic patients (8 males and 10 females, aged 18-26 years, within 10-120 days from the onset of symptoms) who were submitted for 15 days to intensive insulin therapy performed via subcutaneous insulin infusion (CSII). We investigated some metabolic and immunological parameters in order to identify a possible marker to predict the selection of patients potentially more responsive to CSII treatment for the remission of type 1 diabetes. In accordance with the International Diabetes Immunology Group we considered clinical remission as being the withdrawal of insulin therapy for at least 3 months. In order to assess beta-cell function a fasting and post-prandial serum C-peptide, blood glucose and HbA1c were performed on all patients before, and 3 days after, the discontinuation of CSII. Islet cell antibodies were determined in all sera by indirect immunofluorescence. Analysis of T-lymphocyte subpopulations was carried out before starting the therapy. The following monoclonal antibodies were used: CD4, CD8, CD57, CD25, HLA-DR. The levels of C3 and C4 and serum IgG, IgA and IgM were also evaluated. After CSII, 11 of 18 patients showed remission. At the beginning of the study we observed no major difference in metabolic parameters between the two groups. Interestingly, the patients who exhibited remission presented a statistically higher percentage of positive cells for CD57, HLA-DR and CD25 surface antigens, significantly lower C4 levels and CD4/CD8 ratio and significantly higher IgG levels compared with patients who did not show any remission.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Toxicity of some Fusarium section Sporotrichiella strains in relation to mycotoxin production.

The relationship between the toxicities of crude extracts and purified toxins of Fusarium spp. belonging to the section Sporotrichiella has been assessed. Toxicity was determined on the basis of death of Artemia salina larvae and of viability and blastogenic response of bovine and human lymphocytes. Trichothecene-producing strains of Fusarium sporotrichioides and Fusarium poae were toxic to A. salina and to lymphocyte blastogenesis. A strain of Fusarium tricinctum, producing visoltricin and chlamydosporol, induced differentiated activity in different bioassays (toxicity to A. salina but only minor activity against lymphocyte blastogenesis). Other, non-toxin-producing strains of Fusarium chlamydosporum, F. poae, and F. tricinctum were not active in the tested biosystems.

Animals↗

Prediction of recurrence and progression in primary superficial bladder cancer with DNA flow cytometry.

Intravesical chemotherapy has been well established as an effective therapy for recurrent superficial bladder tumors. We investigated the role of flow cytometry as a predictor of tumor recurrence/progression after intravesical chemotherapy. Flow cytometric analysis of nuclear DNA ploidy pattern was performed on 'cold cup' biopsy samples of 52 patients with primary superficial bladder cancer. Cell suspensions, retrieved after mechanical fragmentation, were stained with propidium iodide and examined on FACScan flow cytometer. Clinical follow-up ranged from 3 to 57 months with a median of 20 months. Of the 52 patients, 24 aneuploid and 28 diploid tumors were observed. The degree of ploidy in relation to histological grade showed an increasing frequency of aneuploid pattern in grades 2 and 3 but with no statistical significance. 17.8% of diploid tumors versus 54.1% of aneuploid tumors recurred (p less than 0.05). 12.5% of the aneuploid tumors progressed. No progression among diploid tumors was observed. Of the 52 patients examined, 35 (16 aneuploid and 19 diploid) were treated, after TUR, with intravesical prophylactic therapy. Epirubicin in 24, mitomycin C in 4 and recombinant interferon alpha 2a in 7 were used. 50% of aneuploid tumors versus 10.5% of diploid tumors recurred (p less than 0.05). Strong predictors of response to intravesical prophylaxis of recurrence were G1 grade and diploid DNA content.

Adult↗

Cytotoxic and immunotoxic effects of Fusarium mycotoxins using a rapid colorimetric bioassay.

A colorimetric MTT (tetrazolium salt) cleavage test was used to evaluate cytotoxicity of twenty-three Fusarium mycotoxins on two cultured human cell lines (K-562 and MIN-GL1) as well as their inhibitory effect on proliferation of phytohemagglutinin-stimulated human peripheral blood lymphocytes. The values of 50% inhibition of lymphocyte blastogenesis were very close to the 50% cytotoxic doses observed with the more sensitive cell line (MIN-GL1). T-2 toxin was the most cytotoxic with CD50 and ID50 values less than 1 ng/ml. Type A trichothecenes were the most cytotoxic followed by the type B trichothecenes; the non-trichothecenes were the least cytotoxic. The MTT cleavage test, in conjunction with cell culture, is a simple and rapid bioassay to evaluate cytotoxicity and immunotoxicity of Fusarium mycotoxins.

Cell Line, Transformed↗

Ontogeny of human lymphocytes. Two-color fluorescence analysis of circulating lymphocyte subsets in fetuses in the second trimester of pregnancy.

By using monoclonal antibodies, two-color immunofluorescence techniques and flow cytometry, we evaluated the surface marker phenotypes of lymphocyte subsets in cord blood samples from fetuses in the second trimester of pregnancy. The results indicate that cells of the T-, B- and NK-cell lineages as well as precursor cells can be detected in fetal blood at 18-20 weeks of gestation. At this stage of development, variable proportions of T and B lymphocytes express surface molecules, such as the CD1, CD10, CD38, CD45RA, indicative of a precursor or 'naive' state; on the other hand, the CD57 molecule is not detectable on the membrane of NK and T cells, and the RO isoform of the CD45 leukocyte antigen is synthesized by a low percentage of T cells. We suggest that the observed phenotypic peculiarities of the lymphoid cells might be related to the easy induction of tolerance that occurs in the early ontogenetic stages of the immune system.

Antigens, Differentiation↗

[Interferons in medicine].

In the last decade, recombinant DNA technology and monoclonal antibodies have allowed the production of great amounts of pure interferons that have been used in clinical trials. Presently, interferons have a defined role in the therapy of infectious and malignant disorders and are widely available both to the specialist and the general practitioner. The aim of the present review is to summarize the main biochemical properties and the molecular mechanisms underlying the broad spectrum of the biological activities of the interferons. Furthermore, on the basis of the results obtained in therapeutical trials, the infectious and neoplastic diseases responsive to therapy with interferons are outlined, along with the most frequent side or toxic effects.

Forecasting↗

Age-related changes in the proliferative kinetics of phytohemagglutinin-stimulated lymphocytes. Analysis by uptake of tritiated precursors of DNA, RNA and proteins, and by flow cytometry.

We have examined the age-related changes in the kinetics of lymphocyte proliferative responses to phytohemagglutinin by flow cytometry and by the uptake of tritiated thymidine, uridine and leucine. The lymphocyte suspensions used in these experiments were obtained by umbilical cord blood samples of full-term normal newborns and from the peripheral blood of young (under 30-year-old) or aged (more than 70-year-old) healthy donors. The results indicate that the cord blood lymphocytes were activated by phytohemagglutinin to incorporate tritiated precursors of proteins, RNA and DNA at a more rapid rate than the lymphocytes from young or old donors in the first 3 days of in vitro culture. Flow cytometry confirmed higher percentages of activated cycling cells in umbilical cord blood after 24 h of culture. The lymphocytes from old donors incorporated significantly lower amounts of tritiated precursors of DNA and RNA than lymphocytes from young donors at the third day of culture. The uptake of tritiated leucine by lymphocytes from old donors was significantly reduced up to the sixth day of culture. On the contrary, at the eight day of culture, lymphocytes from old donors incorporated significantly higher amounts of labeled DNA, RNA and protein precursors. In agreement with these findings, flow cytometry demonstrated a trend towards higher percentages of cycling cells in the lymphocyte cultures from old donors after 6 and 8 days. These results indicate an age-related decline in the rate of lymphocyte blastogenesis after in vitro PHA stimulation and suggest that after a delayed PHA-induced activation, the lymphocytes from aged donors have a near-normal ability to proliferate.

Adult↗

Lymphocyte subsets in peripheral blood and pleural fluid.

We have examined the distribution of B and T lymphocytes, T-cells with helper/inducer (T4+) or suppressor/cytotoxic (T8+) phenotypes and a subset of cells with natural killer (NK) activity and positive for the Leu 7 (HNK-1) surface antigen in peripheral blood and in lymphocyte-rich pleural effusions of patients with tuberculosis or malignancies (mesothelioma and lung cancer with pleural metastasis). In individual patients, the percentages of T lymphocytes were uniformly higher in pleural effusions than in peripheral blood; however, lower percentages of B lymphocytes and cells positive for the Leu 7 antigen were present in pleural fluids. The analysis of T-cell subpopulations demonstrated a selective enrichment of T lymphocytes with helper/inducer phenotype in pleural effusions, while the percentages of T-cells with suppressor/cytotoxic phenotype were similar in pleural fluid and peripheral blood. These results indicate that in lymphocytic pleural effusions the main lymphoid cell population is represented by T lymphocytes with helper/inducer phenotype, regardless of whether the effusion is due to tuberculosis or malignancies such as mesothelioma or lung cancer.

Adult↗