Search PubMed⌕ Search

Biomedical subjects

G Leone

Publications and source records attributed to G Leone.

At least 109 records · Page 6Linked to original sources
PubMed2000

Interaction between hyperhomocysteinemia and inherited thrombophilic factors in venous thromboembolism.

Hyperhomocysteinemia is an established risk factor for deep vein thrombosis. Factor V Leiden has been reported to potentiate the thrombotic risk related with severe hyperhomocysteinemia, being more represented in thrombotic patients with homocystinuria as compared with patients without a history of thrombosis. The results concerning the interaction between moderate hyperhomocysteinemia and inherited thrombophilic factors such as Factor V Leiden or the prothrombin G20210A mutation are contradictory. The relative risk for venous thrombosis has been reported to be increased 10- to 50-fold in patients carrying both hyperhomocysteinemia and inherited thrombophilia in comparison with normal controls, suggesting a synergistic interaction, yet other studies failed to confirm such conclusion. The heterogeneity of these findings is in part due to the small number of individuals with double defects, leading to statistically unreliable results. Genotyping for mutations that are possible causes of moderate hyperhomocysteinemia, such as the thermolabile variant (C677T) of methylenetetrahydrofolate reductase (MTHFR), does not seem useful to identify individuals at higher risk for venous thromboembolism. In fact, in most of the studies the presence of the C677T MTHFR homozygous genotype does not increase the thrombotic risk associated with Factor V Leiden or the prothrombin mutation.

3' Untranslated Regions↗
PubMed2000

Enhanced susceptibility to apoptosis in T cells recovering after autologous peripheral blood progenitor cell transplantation: reversal by interleukin-15.

T-cell number and competence are profoundly impaired after transplantation of autologous cytokine-mobilized peripheral blood progenitor cells (PBPC). The objective of the present study was to evaluate the occurrence of T-cell spontaneous apoptosis (Aspont) and its modulation in vitro by the interleukin-2 receptor (IL-2R) gamma-chain (gammac)-signaling cytokine interleukin-15 (IL-15) in the peripheral blood of patients transplanted with autologous PBPC for hematological malignancies. An average 45%+/-6% of CD4+ and 55%+/-6% of CD8+ T cells cultured in the absence of exogenous cytokines underwent Aspont; of interest, IL-15 and, to a lesser extent, its structural cousin IL-2 counteracted T-cell Aspont and upregulated Bcl-2 levels. IL-15 did not rescue T cells from Aspont by promoting proliferation, but rather it acted as a genuine survival factor. Furthermore, T-cell preincubation with a gammac-blocking antibody was capable of abrogating both apoptosis inhibition and Bcl-2 induction by IL-15. These in vitro findings suggest that IL-15 might represent a promising immunomodulating agent to improve T-cell function after autologous PBPC transplantation.

Adult↗
PubMed2000

Autologous graft-versus-host disease after CD34+-purified autologous peripheral blood progenitor cell transplantation.

Autologous graft-versus-host disease (GVHD) has been frequently reported after cyclosporine A (CsA) administration in the autologous setting. This complication is related to the disruption of self-tolerance mechanisms induced by CsA and may exert an antitumor effect. We report the spontaneous occurrence of autologous GVHD after CD34+-purified peripheral blood progenitor cell transplantation (PBPCT) in 5 out of 24 consecutive patients (20.8%). The syndrome was characterized by skin rash (5/5), pruritus (5/5), eosinophilia (5/5), and fever (2/5) occurring at a median of 37 days (range 22-60) after transplantation. Diagnosis was confirmed by skin biopsy in all patients. The syndrome was self-limiting, lasted a median of 25 days, and did not require treatment. The rate of autologous GVHD was high after CD34+-purified autologous PBPCT. In fact, no autologous GVHD was documented in an historical control of 100 consecutive patients submitted to unmanipulated PBPCT at the same institution. The manipulation of the graft by the purging procedure causes a profound T lymphocyte depletion, thus possibly perturbing the equilibrium between autoregulatory cells and autocytotoxic T cells. These observations add new interest to the antitumor efficacy of autologous GVHD and suggest new questions regarding the role of transplantation for autoimmune diseases.

Adolescent↗
PubMed2000

Prevalence of factor V Leiden and the G20210A prothrombin-gene mutation in inflammatory bowel disease.

A hypercoagulable state has been hypothesized as a contributing factor in the pathogenesis of inflammatory bowel disease (IBD); moreover, such patients have an increased risk of thrombotic complications. The aim of the present paper was to study the prevalence of the two most important causes of inherited thrombophilia: factor V Leiden and the G20210A prothrombin-gene mutation in patients with Crohn's disease (CD) and ulcerative colitis (UC). Fifty-two patients affected by IBD (33 UC and 19 CD, 16 female and 36 male; mean age, 42 years) and 156 healthy controls (48 female and 108 male; mean age, 37 years) were studied. Seven out of 52 patients (13%) had previous thrombotic events. High molecular weight DNA was analysed for the presence of factor V Leiden and the G20210A prothrombin-gene mutation. One out of 52 IBD patients (1.9%) and three out of 156 control subjects (1.9%) were heterozygous for factor V Leiden. One IBD patient (1.9%) and four healthy controls (2.6%) were heterozygous for the prothrombin-gene mutation. The prevalence of the two mutations was similar in patients and controls. In the subgroup of IBD patients with previous thrombotic events, only one patient was heterozygous for the prothrombin-gene mutation. Factor V Leiden and the G20210A prothrombin-gene mutation do not seem to play a major role in the pathogenesis of IBD or be associated with an increased incidence of thrombotic complications, but with limited data.

Adult↗
PubMed2000

Identification of a novel E2F3 product suggests a mechanism for determining specificity of repression by Rb proteins.

The tumor suppressor function of Rb is intimately related to its ability to interact with E2F and repress the transcription of E2F target genes. Here we describe a novel E2F product that specifically interacts with Rb in quiescent cells. This novel E2F, which we term E2F3b, is encoded by a unique mRNA transcribed from an intronic promoter within the E2F3 locus. The E2F3b RNA differs from the previously characterized E2F3 RNA, which we now term E2F3a, by the utilization of a unique coding exon. In contrast to the E2F3a product that is tightly regulated by cell growth, the E2F3b product is expressed equivalently in quiescent and proliferating cells. But, unlike the E2F4 and E2F5 proteins, which are also expressed in quiescent cells and form complexes with the p130 protein, the E2F3b protein associates with Rb and represents the predominant E2F-Rb complex in quiescent cells. Thus, the previously described specificity of Rb function as a transcriptional repressor in quiescent cells coincides with the association of Rb with this novel E2F product.

Base Sequence↗
PubMed2000

Complex transcriptional regulatory mechanisms control expression of the E2F3 locus.

E2F transcription activity has been shown to play a critical role in cell growth control, regulating the expression of a variety of genes that encode proteins important for the initiation of DNA replication and cell cycle regulation. We have shown that the E2F3 locus encodes two protein products: the E2F3a product, which is tightly regulated by cell growth, and the E2F3b product, which is constitutively expressed throughout the cell cycle. To further explore the mechanism controlling the expression of the two E2F3 gene products, we analyzed the genomic sequences flanking the 5' region of E2F3a and E2F3b. We find that a series of E2F binding sites confer negative control on the E2F3a promoter in quiescent cells, similar to the control of the E2F1 and E2F2 promoters. In addition, a group of E-box elements, which are Myc binding sites, confer responsiveness to Myc and are necessary for full activation of the E2F3a promoter in response to growth stimulation. Based on these results and past experiments, it appears that the E2F1, E2F2, and E2F3a genes are similarly regulated by growth stimulation, involving a combination of E2F-dependent negative control and Myc-mediated positive control. In contrast, the constitutive expression of the E2F3b gene more closely reflects the control of expression of the E2F4 and E2F5 genes.

Base Sequence↗
PubMed2000

Second-order iterative approach to inverse scattering: numerical results

We introduce an iterative algorithm for the reconstruction of dielectric profile functions from scattered field data, in which each step corresponds to the solution of a quadratic inversion problem. This means that, at each iteration, we perform a second-order approximation of the scattering operator connecting the unknown profile to the data about a reference profile function. This procedure is then compared with a linear iterative inversion algorithm, and it is pointed out that, within a prescribed class of profile functions, the linear iterative inversion does not converge to the actual solution, whereas the proposed approach does. This feature can be explained by reference not only to the improved approximation provided by the addition of a further term for profile functions of a larger norm but also to the different classes of functions that can be reconstructed by either the linear or the quadratic model. Numerical examples of profile reconstruction in the scalar two-dimensional geometry, with far-zone scattered field data at a fixed frequency, confirm the theoretical analysis.

Journal Article↗
PubMed2000

Clinical and epidemiological features of acute lymphoblastic leukemia following a previous malignancy.

Secondary malignancies represent a relevant complication of chemotherapy employed for a previous cancer. Acute leukemias represent the most frequent secondary malignancy in the first decade following primary neoplasms; secondary leukemias are generally myeloid and can be preceeded by a myelodysplastic syndrome. The biological and epidemiological characteristics of secondary acute myeloid are well known and have been the subject of numerous reports and reviews in the last few years. The observation of a secondary acute lymphoblastic leukemia is considered rare, and the correlation with antecedent therapies is not definitive. Most of reported cases are single reports, and no large study has been performed to investigate the real importance of this problem. In this review we report data of the current literature on secondary acute lymphoblastic leukemia, both in adults and children, in order to analyze its incidence and clinical and laboratory features.

Adult↗
PubMed2000

Autologous peripheral blood stem cell transplantation as first line treatment of multiple myeloma: an Italian Multicenter Study.

BACKGROUND AND OBJECTIVE: The outcome of patients with multiple myeloma (MM) has not changed markedly since the introduction of melphalan and prednisone. In recent years several studies have investigated the role of intensive therapy followed by infusion of autologous peripheral blood stem cells (PBSC) together with the administration of hematopoietic growth factors. In this study we evaluated the feasibility and efficacy of a PBSC transplantation program for patients with de novo MM in a multicenter setting. DESIGN AND METHODS: In a non-randomized controlled trial 52 patients with de novo MM from 6 Italian centers underwent a three phase treatment strategy including 3 cycles of VAD-like chemotherapy for initial debulking, followed by high-dose cyclophosphamide (HD-CY) and collection of PBSC, that were transplanted after a conditioning regimen with melphalan plus busulfan. Maintenance treatment was a conventional dose of interferon, given until relapse. Actuarial survival and response duration curves were plotted according to Kaplan and Meier's method; the groups were compared using the log rank test. Response rates were compared by the c(2) test; multivariate analysis was performed according to the stepwise regression model. RESULTS: Overall 39/52 (75%) of patients responded, with a complete remission (CR) rate of 31%. After a median follow-up of 55 months, median duration of event-free survival (EFS) and overall survival (OS) are 21 and 57 months, with 24% and 48% probabilities of being event-free and alive after 6 years, respectively. Among the group of 39 responders, CR was significantly associated with prolonged response and survival (2 deaths and 6 relapses/16 patients) as compared with PR (11 deaths and 15 relapses/23 patients), and remained the only significant variable also in a multivariate analysis. Myelosuppression did not protract beyond one week in transplanted patients; extra-hematologic toxicity was very low. INTERPRETATION AND CONCLUSIONS: This multicenter study confirms the feasibility of an aggressive approach to de novo MM patients. Additional confirmation is given of the increased rate of CR, and the significant prolonged survival observed in complete responders. In this experience the association melphalan plus busulfan was shown to be effective, at least as part of conditioning regimens, in the transplant strategy.

Adult↗
PubMed2000

Lymphoid blastic crisis in Philadelphia chromosome-positive chronic granulocytic leukemia following high-grade non-Hodgkin's lymphoma A case report and review of literature.

In this paper we describe a case of a 65-year old man with a lymphoid blastic crisis of a chronic granulocytic leukemia occurring seven years after a palatine tonsillar non-Hodgkin's lymphoma treated with chemotherapy and radiation therapy. Bone marrow cytogenetic study demonstrated the presence of the typical t(9;22)(q34;q11) and the molecular biology study showed the p210 rearrangement (b2a2). The patient died within a few months, unresponsive to any treatment. This is the first case, described in literature, of a secondary chronic granulocytic leukemia onset with a lymphoid blastic crisis. The authors report the case and a literature review.

Aged↗
PubMed2000

Bax mutations are an infrequent event in indolent lymphomas and in mantle cell lymphoma.

BACKGROUND AND OBJECTIVES: The Bax gene is one of the most important genes involved in apoptosis regulation. Recently, it has been proposed that inactivating mutations of this death agonist may contribute to the pathogenesis of human tumors. This study was aimed at defining the status of the Bax gene in indolent lymphomas. DESIGN AND METHODS: Fifty paraffin-embedded biopsies from indolent lymphomas (10 small lymphocytic lymphomas, 5 immunocytomas, 20 follicular lymphomas and 15 marginal zone lymphomas) and 10 mantle cell lymphomas ( MCL ) were studied. All six exons of the Bax gene, together with their flanking sequences, underwent mutational analysis by PCR-SSCP followed by direct sequencing of positive cases. Moreover, Bax protein expression was investigated in all samples by immunohistochemical analysis. RESULTS: All analyzed cases showed wild type Bax gene alleles and variable levels of Bax protein expression. INTERPRETATION AND CONCLUSIONS: This study indicates that deregulation of apoptotic control in indolent lymphomas and MCL is not caused by Bax mutations and that other molecular mechanisms must, therefore, be involved.

Gene Frequency↗
PubMed2000

Stem cell collection using the dideco excel continuous flow blood cell separator: parameters for optimal stem cell collection timing.

This study evaluates stem cell collection procedures performed with the Dideco Excel blood cell separator, with particular attention given to yields and separator collection efficiencies. Patients' blood precounts and yield parameters related to the harvest capacity of the collection system were investigated. Fifty-five collection procedures were analyzed in 32 patients suffering from hematological malignancies and solid tumors and mobilized with chemotherapy plus G-CSF. The median blood volume processed in each procedure was 15.8 liters (12-19.750), with a blood flow rate of 70 ml/min. Patients had the following median blood precount value: NC 7.81x10(9)/L, CD34+ cells 49.08x10(3)/ml. Leukapheresis procedures gave the following yields: NC 14.95x10(9), MNC 10.83x10(9), CD34+ cells 4.37x10(6); yields/kg, NC 0.21x10(9)kg, MNC 0. 15x10(9)/kg CD34+ cells 4.26x10(6)/kg. Procedures show the following collection efficiencies: NC 10.79%, MNC 29.06%, CD34+ 42.33%, PLT 26.5%. The RBC (red blood cell) contamination of the product was (median value) 20.9 ml for each procedure, and for platelets 1.76x10(11) per procedure. The CD34+ cell precounts strongly correlated with the CD34+ yields/kg (r=0.82. p=0.000). Furthermore the NC and MNC precounts correlated with the CD34+ yields/kg but only the MNC precount correlation is notable (r=0.57, p=0.000). The logistic regression analysis shows that CD34+ (p=0.008) but not NC (po=0.14), MNC (p=0.09), or PLT (p=0.53) precounts significantly influenced the collection of a sufficient dose of CD34+ cells for transplantation (> or =2.5x10(6)/kg). Eleven of the thirty-two patients have been transplanted till now, and all had a prompt and lasting trilineage engraftment NC >1x10(9)/L on day 12 (10-17). Our data show that the collection system analyzed in this report is able to collect large amounts of progenitor cells, harvesting >2.5x10(6)/kg CD34+ cells with a single procedure in 68.8% of patients and assuring complete recovery after stem cell transplantation.

Adolescent↗
PubMed2000

Acute lymphoblastic leukemia in the elderly. A twelve-year retrospective, single center study.

Acute myeloid leukemia in elderly patients is a well-studied disease, while only a few studies on acute lymphoid leukemia (ALL) in elderly patients have been reported and their results are not encouraging. The aims of the present study were to review the characteristics of acute lymphoblastic leukemia developing in patients aged over 65 years old during a twelve-year period at our Institution and to analyze the clinical and laboratory characteristics.

Aged↗
PubMed2000

Induction of DNA replication in adult rat neurons by deregulation of the retinoblastoma/E2F G1 cell cycle pathway.

In adult organisms, a range of proliferative capacities are exhibited by different cell types. Stem cell populations in many tissues readily enter the cell cycle when presented with serum growth factors or other proliferative cues, whereas "terminally" postmitotic cells, such as cardiac myocytes and neurons, fail to do so. Although they rarely show evidence of a proliferative capacity in vivo, there is accumulating evidence to suggest that DNA synthesis can be triggered in postmitotic cells. We now show that cultured adult rat sensory neurons can replicate DNA in response to ectopic expression of E2F1 or E2F2 and that this is augmented by expression of cyclin-dependent kinase activities. We also find that addition of serum and laminin inhibits the E2F-induced S-phase in neurons but not in nonneuronal cells in the same cultures. We conclude that, although terminally differentiated neurons possess the capacity to reinitiate DNA replication in response to G1 regulatory activities, they fail to do so in the presence of signals that do not inhibit S-phase in other cell types in the same cultures. This suggests the existence of cell type-specific inhibitory pathways induced by these signals.

Adenoviridae↗