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G Leone

Publications and source records attributed to G Leone.

At least 181 records · Page 10Linked to original sources
PubMed1998

The Hohn catheter in the management of haemopoietic stem cell transplant recipients.

Patients undergoing bone marrow transplantation require a reliable venous access. The authors have tested the feasibility and safety of a new, silicone, open-ended, non-tunnelled central venous catheter (CVC), the Hohn catheter (Bard Access System, USA). From January 1994 to December 1996, 58 Hohn were inserted into 56 bone marrow transplant (BMT) patients (26 women: 30 men; mean age 38 years, range 19-62 years). The CVC was inserted percutaneously at the bedside by puncture of the subclavian or the internal jugular vein. No early complications were observed. Significant late complications were infection (documented only in 14%) and accidental removal (11%). The median life of the CVC was 30 days (range 15-180 days). Major causes of removal were end of use (25 patients) and fever (19 patients; but infection was documented only in eight patients). In spite of the relatively small gauge (5 Fr), the Hohn catheter was adequate for rapid or high density infusion. In our experience, the unique features of the Hohn CVC (versatility, optimal biocompatibility, bedside management, low cost) may contribute to making the BMT procedure safer and less expensive.

Adult↗
PubMed1998

Epidemiology of factor V Leiden: clinical implications.

Inherited resistance to activated protein C (APC) has been recently recognized as a novel cause underlying venous thrombophilia. In most cases APC resistance is due to a single point mutation in the factor V gene leading to a replacement of Arg506 with Gln (factor V Leiden). Factor V Leiden allele is present in about 5% of the Caucasian individuals (Europeans, Jews, Israeli Arabs, and Indians) and is virtually absent in Africans, Asians, and races with Asian ancestry such as Amerindians, Eskimos, and Polynesians; this suggests a single origin of the mutation, which has been proven by haplotype analysis. A low prevalence of the mutation (1%) was noticed in African-Americans for recent racial admixture. Factor V Leiden presents not a major role as risk factor for arterial thrombosis, while it is present in 18% of Caucasian patients with venous thrombosis. This high incidence prevalence mirrors the incidence in the corresponding general populations and can be even higher in some areas according to the ethnic background. Conversely, factor V Leiden is usually not found in non-Caucasian thrombotic patients; this could give reason of the lower incidence of venous thrombotic disease in Africa and Asia in comparison with Europe. Therefore, screening for factor V Leiden is suggested for all Caucasian individuals with previous venous thrombosis; inclusion criteria for the screening should not be stringent because clinical manifestations associated with the mutant genotype can be also mild or secondary to circumstantial risk factors or manifesting at advanced age. Factor V Leiden can act also as concurrent risk factor in individuals with deficiency of natural inhibitors or mild hyperhomocysteinemia. So far, screening for the mutation in individuals with no history of thrombosis is recommended only for relatives of proband patients identified as carriers; the available data do not justify indiscriminate screening before risk situations such as oral contraceptives intake, pregnancy, or high-risk surgery.

Factor V↗
PubMed1998

Incidence of sepsis after peripheral blood progenitor cells transplantation: analysis of 86 consecutive hemato oncological patients.

The incidence of documented infections after autologous peripheral blood progenitor cells transplantation (PBPCT) was retrospectively evaluated in 86 consecutive patients (47 males 39 females; median age 36 years, range, 18-63) treated in our institution; 83 patients had refractory hematological malignancies (40 non-Hodgkin's lymphoma, 19 Hodgkin's disease, 17 multiple myeloma, 7 acute myeloblastic leukemia) and 3 had solid tumors (1 rabdomyosarcoma, 1 neuroblastoma, 1 osteosarcoma). All patients developed fever after transplantation lasting a median of 2 days (range 1-17); 20 instances of documented sepsis developed in 17 patients (19.7%). Gram positive microorganisms were implicated in all but 4 cases. There were no fatalities directly due to infections and no correlation was found between the risk of infection and reaching PMN > 0, 1 x 10(9)/L, PMN > 0.5 x 10(9)/L. In addition no specific risk factors related to age, disease, conditioning regimen, use of central venous catheter (CVC), type of transplant, and isolation measures were identified.

Adolescent↗
PubMed1998

Immunophenotypic profile of peripheral blood eosinophils in acute graft-vs.-host disease.

We used a flow cytometry technique, the "FOG" method (formaldehyde and octylglucopyranoside), to investigate the expression of activation antigens, i.e., CD4, CD23, CD25, HLA-DR, and the EG2 epitope of eosinophilic cationic protein, on peripheral blood eosinophils (PBEs) in leukemic patients who had developed acute graft-vs.-host disease (aGVHD) with eosinophilia after allogeneic bone marrow transplantation (alloBMT) or leukocyte buffy coat infusion. A comparative analysis was performed in transplanted patients not affected by aGVHD and in other conditions commonly associated with peripheral eosinophilia, i.e., interleukin (IL)-2 immunotherapy and allergy. CD25, recognizing the p55 subunit of IL-2 receptor, was detected in all patients with aGVHD except two who, at the onset of eosinophilia, were already receiving methylprednisolone intravenously. The specificity of our findings is confirmed by the absence of reactivity with anti-CD25 mAb in PBEs from transplanted patients not affected by aGVHD. Interestingly, the expression of CD25 progressively declined after steroid therapy. CD25 was also expressed after rhIL-2 administration, probably reflecting analogous mechanisms of eosinophil activation. No aGVHD or rhIL-2-treated patient showed reactivity with anti-CD4, CD23, or HLA-DR. CD25 and CD23 antigens were detected in 29% and 36% of allergic patients only. The accessibility of the EG2 epitope was significantly enhanced in all study groups compared with controls. In vitro activation of normal eosinophils with phorbol 12-myristate 13-acetate upregulated CD9 and EG2 expression but failed to induce the CD25 antigen, suggesting that selective activating stimuli may be required. The functional significance of in vivo CD25 expression and the role of activated PBEs in the development of cellular and cytokine-mediated tissue destructive processes in aGVHD remain to be clarified.

Adolescent↗
PubMed1998

E2F1-specific induction of apoptosis and p53 accumulation, which is blocked by Mdm2.

Previous work has demonstrated a role for E2F transcription factor activity in the regulation of cell growth during the G0/G1-S phase transition. Indeed, overexpression of E2F proteins, including the E2F1 and E2F2 products, induces DNA synthesis in quiescent fibroblasts. Other experiments have shown that E2F1 expression also induces apoptosis, dependent on p53. Although this could represent a response to aberrant cell cycle progression, we show that only E2F1 induces apoptosis and that this coincides with an ability of E2F1 to induce accumulation of p53 protein. We also find that coexpression of Mdm2, which is known to regulate p53 activity, blocks the E2F1-mediated induction of apoptosis and also blocks the E2F1-mediated accumulation of p53. We propose that E2F1 acts as a specific signal for the induction of apoptosis by affecting the accumulation of p53, which under normal proliferative conditions may be controlled by Mdm2.

Adenoviridae↗
PubMed1998

Assessment of hematological and immunological function during long-term follow-up after peripheral blood stem cell transplantation.

BACKGROUND AND OBJECTIVE: Long-term hemopoietic and immunological profile after autologous peripheral blood progenitor cells transplantation (PBPCT), in patients affected by hematological malignancies is largely unknown. The aim of this work was to detect the impact of high dose chemotherapy and PBPCT on hemopoietic and immunological function compared to conventional chemotherapy. DESIGN AND METHODS: Patients had to fulfill the following criteria: continuous complete remission after PBPCT, follow-up longer than 12 months, no chemo or radiotherapy or biological response modifiers after PBPCT. Twenty-five patients were considered eligible for this analysis. Stable and complete hemopoietic reconstitution (Hb > 12 g/dL, WB > 4.0 x 10(9)/L, ANC > 1.5 x 10(9)/L and Pits count > 150 x 10(9)/L), morphological examination of peripheral blood and bone marrow, cytogenetic analysis and immunological profile were evaluated at 12 months and yearly thereafter. RESULTS: Immunological reconstitution showed a persistent reduction of CD4/CD8 ratio up to five years after PBPCT. This reduction was related to a persistent increase of CD8+ lymphocytes and a constant reduction of CD4+ lymphocytes. INTERPRETATION AND CONCLUSIONS: Defects observed in PBPCT patients are induced by the procedure itself, by the conditioning regimen or both. The different behavior in the immune reconstitution of CD8+ subset after PBPCT may be favored by an extrathymic origin of these cells while CD4+ subset recovery which is thymus-dependent is impaired after PBPCT in adult population. Long-term hemopoietic reconstitution after PBPCT is rapidly obtained and is stable over the years, long-term immunological function seems to be abnormal in these patients and these abnormalities are long-lasting.

Adult↗
PubMed1998

Distinct mechanisms control the accumulation of the Rb-related p107 and p130 proteins during cell growth.

A variety of studies have demonstrated the critical role of the Rb/E2F pathway in the control of cell growth and have highlighted a complexity in the accumulation of both the E2F family proteins and the Rb family of proteins. Whereas the Rb protein is found in both growing and quiescent cells, the accumulation of p130 and p107 is tightly regulated with respect to the growth state of the cell. The p130 protein is found in quiescent cells but not in growing cells, whereas the inverse is true for the p107 protein. Control of p130 accumulation is posttranscriptional, because p130 RNA is relatively constant in growing and quiescent cells. The disappearance of the p130 protein after stimulation of cell growth coincides with cyclin-dependent kinase-mediated phosphorylation and is blocked by inhibitors of the 26S proteasome. In contrast, the cell growth-dependent regulation of p107 expression reflects the transcriptional regulation of the p107 gene. Similar to several other growth-regulated genes, the control of p107 expression is largely the result of E2F-dependent repression in quiescent cells. These experiments thus demonstrate a control of Rb family member expression mediated through distinct mechanisms of both transcriptional and posttranslational control and also suggest an intimate relationship in which p130 controls the expression of p107.

Adenoviridae↗
PubMed1998

[Functional urination disorders in patients recovering in an intensive care unit for more than 30 days].

Patients in rest-homes, intensive care units, long hospitalization and dialysis and whoever stays in a hospital continuously or occasionally for long periods of time may run into the well-known and typical complications of prolonged hospitalization. We have studied the urologic aspect in all the cases of the Medical- Surgical Emergency Institute in the Hospital of Ancona (seated in Torrette), over the period 1990-96, in patients hospitalized for at least 30 days. All the patients were followed and studied with the same method, though taking into account their different pathological conditions. They were treated by the same medical and paramedical staff. The same antibiotic therapy and the same checkup were adopted for all of them. We have noticed that out of 122 patients the most frequent pathologies have been urinary infections (19%); while sepsis with different pathogenesis was recorded in 4% of the patients. The method of study applied during and after the hospitalization was used also in rehabilitation centres and included: urologic examination, rectal touch (in men), direct X-ray of the abdomen, ultrasound of the urinary tract, X-ray urography, if required; moreover urodynamic examination, MRI of encephalon and spinal marrow in patients with neurological lesions. The catheter was removed in all the patients and none of the following conditions were observed: vesical lithiasis, abscesses, fistulae in penoscrotal angle, urethrostenosis, injuries to renal emunctory. In conclusion we believe that the functional symptoms of minction--be they of obstructive or irritable nature--are not existent and that the urologic prognosis in long term patients in excellent, provided that prophylaxis is carried on against hospital urinary infections as their occurrence is very frequent and therapy is expensive. It can also be stated the patient hospitalized in ICU will not present damages to the urinary tract, even if he/she has been hospitalized because of injuries to the urinary tract, provided that the urologic tutoring, together with the action of the physician handling the Emergency, follow the rules for asepsis, the best biocompatible materials are use, infections are monitored, the extensions of cerebrospinal injuries are examined and therapeutic axioms, such as barren and clean intermittent catheterism, are finally adopted.

Adolescent↗
PubMed1998

Serum of healthy donors receiving granulocyte colony-stimulating factor induces T cell unresponsiveness.

The effects of serum from healthy donors receiving recombinant human granulocyte colony-stimulating factor (rhG-CSF) (G-serum) on blast transformation, expression of activation-related antigens, secretion of interleukin (IL)-2, and proliferation were evaluated in allogeneic lymphocytes stimulated with phytohemagglutinin. Escalating concentrations of G-serum induced 27%, 47%, and 70% suppression of lymphocyte proliferation; interestingly, CD4+ and CD8+ cells underwent blast transformation and up regulated early (CD69) and late (CD25, HLA-DR, and CD71) activation-related antigens. Negligible fractions of apoptotic cells were found after mitogenic challenge, suggesting that the strongly diminished proliferation was not attributable to extensive activation-induced programmed cell death of responding T cells. The levels of IL-2 in cultures containing G-serum were comparable to those in cultures performed without G-serum; however, high concentrations of exogenous IL-2 restored lymphocyte mitogenesis regardless of G-serum concentration. These findings--cell enlargement, upregulation of activation-related antigens, inability to proliferate after mitogenic stimulus, and restoration of cell division by exogenous IL-2--resembled those associated with "partial activation" of lymphocytes, a fundamental control mechanism of tolerance induction in T cell clones. Soluble immunoregulatory mediators infused with allogeneic hematopoietic progenitor products collected after rhG-CSF administration could induce T cell unresponsiveness in vivo, thus preventing clonal expansion and amplification of immune responses, and could account for the unexpectedly reduced incidence and severity of graft vs. host disease compared with allogeneic marrow infusion.

Adult↗
PubMed1998

Expression of p15INK4B in normal hematopoiesis.

The cyclin-dependent kinase inhibitor (CDKI) p15INK4B (p15) induces cell cycle arrest in G0/G1 phase. Several studies report deletion or transcriptional loss of the p15 gene in myeloid and lymphoid hematological malignancies, and a possible role as a tumor suppressor gene has been proposed for this CDKI. In this study we evaluated the expression of p15 by cytofluorometric, immunohistochemical, and reverse transcriptase-polymerase chain reaction (RT-PCR) methods in CD34+ progenitors (both during steady state and after chemotherapy and/or granulocyte-colony stimulating factor [G-CSF] administration) and in cells belonging to different hematopoietic differentiative lineages. We found that p15 is not expressed in normal G0/G1-arrested peripheral blood (PB)- or bone marrow (BM)-CD34+ cells. Moreover, p15 is expressed in G0/G1-blocked CD34+ cells mobilized by chemotherapy and G-CSF but not in CD34+ cells mobilized by G-CSF alone. To clarify the role of p15 in normal hematopoiesis, we used flow cytometry to investigate its expression in normal differentiating BM and PB cells. We found that p15 was expressed in cells belonging to the granulocyte-monocyte lineage and in B and T lymphocytes, whereas erythroid and megakaryocytic cells were p15 negative. These findings, which were confirmed both by immunohistochemical and RT-PCR analysis, definitely establish a linkage between p15 expression and granulocyte-monocyte differentiation.

Antigens, CD34↗
PubMed1997

Differential sensitivity of leukemic and normal hematopoietic progenitors to the killing effect of hyperthermia and quercetin used in combination: role of heat-shock protein-70.

Autologous bone-marrow transplantation (ABMT) is widely used in the treatment of acute leukemias where a matched sibling donor is not available for allogeneic transplantation. However, a major problem in ABMT is relapse, and ex vivo purging may be very important in preventing it. We show here that quercetin enhances the growth-inhibitory effect of hyperthermia (HT) in AML (19 cases) and ALL (6 cases) leukemic blasts. Furthermore, the inhibitory effect of this combined treatment resulted in leukemic-cell apoptosis. On the contrary, normal hematopoietic progenitors were neither growth-inhibited nor induced to apoptosis by HT-plus-quercetin treatment. To explain this difference in sensitivity of leukemic and normal hematopoietic progenitors, we analyzed the effect of quercetin on heat-induced expression of heat-shock protein-70 (HSP-70), which has been shown to be important in regulating thermosensitivity. We found that quercetin inhibits heat-induced HSP-70 expression both at protein and at mRNA levels in AML and ALL blasts. In normal CD34+ progenitors, the combined treatment with HT and quercetin did not reduce HSP-70 expression and did not induce cell apoptosis. Considering the difference in heat sensitivity of normal CD34+ and leukemic progenitors in the presence of quercetin, the combined use of HT and quercetin could constitute a purging protocol for ABMT.

Adult↗
PubMed1997

Distinct roles for E2F proteins in cell growth control and apoptosis.

E2F transcription activity is composed of a family of heterodimers encoded by distinct genes. Through the overproduction of each of the five known E2F proteins in mammalian cells, we demonstrate that a large number of genes encoding proteins important for cell cycle regulation and DNA replication can be activated by the E2F proteins and that there are distinct specificities in the activation of these genes by individual E2F family members. Coexpression of each E2F protein with the DP1 heterodimeric partner does not significantly alter this specificity. We also find that only E2F1 overexpression induces cells to undergo apoptosis, despite the fact that at least two other E2F family members, E2F2 and E2F3, are equally capable of inducing S phase. The ability of E2F1 to induce apoptosis appears to result from the specific induction of an apoptosis-promoting activity rather than the lack of induction of a survival activity, because co-expression of E2F2 and E2F3 does not rescue cells from E2F1-mediated apoptosis. We conclude that E2F family members play distinct roles in cell cycle control and that E2F1 may function as a specific signal for the initiation of an apoptosis pathway that must normally be blocked for a productive proliferation event.

Animals↗
PubMed1997

Randomized trial with or without granulocyte colony-stimulating factor as adjunct to induction VNCOP-B treatment of elderly high-grade non-Hodgkin's lymphoma.

Age is an important prognostic parameter, especially in patients with advanced high-grade non-Hodgkin's lymphoma (HG-NHL) who require more intensive and extensive therapy for any possible chance of cure. We investigated the potential of granulocyte colony-stimulating factor (G-CSF) for reducing myelotoxicity, which is the most important dose-limiting factor for chemotherapy. Between March 1993 and June 1995, 158 previously untreated patients 60 years and older with HG-NHL were included in a cooperative randomized comparative trial and treated with a combination therapy including VNCOP-B (cyclophosphamide, mitoxantrone, vincristine, etoposide, bleomycin, and prednisone) with or without G-CSF. G-CSF was administered at 5 microg/kg/d throughout the treatment starting on day 3 of every week for 5 consecutive days. Of the 158 patients registered for the trial, 149 patients were evaluable: 77 received VNCOP-B plus G-CSF and 72 received VNCOP-B alone. The overall response rate was 81.5%, with complete response in 59%: 60% in the VNCOP-B plus G-CSF group, and 58% in the VNCOP-B group. At 30 months (median 24 months), 68% of all complete responders were alive without disease in the G-CSF group and 65% in the control group. Neutropenia occurred in 18 out of 77 (23%) of the G-CSF treated patients and in 40 out of 72 (55.5%) of the controls (P = .00005). Clinically relevant infections occurred in 4 out of 77 (5%) of the G-CSF group and in 15 out of 72 (21%) of the controls (P = .004). The delivered dose intensity was higher in patients receiving G-CSF (95% v 85%), but the difference was not statistically significant. Our data show that VNCOP-B is a feasible and effective regimen in elderly HG-NHL patients, and that the use of G-CSF reduces infection and neutropenia rates without producing any significant modifications to the dose intensity, CR rate, and relapse-free survival curve.

Age Factors↗
PubMed1997

Myc and Ras collaborate in inducing accumulation of active cyclin E/Cdk2 and E2F.

Considerable evidence points to a role for G1 cyclin-dependent kinase (CDK) in allowing the accumulation of E2F transcription factor activity and induction of the S phase of the cell cycle. Numerous experiments have also demonstrated a critical role for both Myc and Ras activities in allowing cell-cycle progression. Here we show that inhibition of Ras activity blocks the normal growth-dependent activation of G1 CDK, prevents activation of the target genes of E2F, and results in cell-cycle arrest in G1. We also show that Ras is essential for entry into the S phase in Rb+/+ fibroblasts but not in Rb-/- fibroblasts, establishing a link between Ras and the G1 CDK/Rb/E2F pathway. However, although expression of Ras alone will not induce G1 CDK activity or S phase, coexpression of Ras with Myc allows the generation of cyclin E-dependent kinase activity and the induction of S phase, coincident with the loss of the p27 cyclin-dependent kinase inhibitor (CKI). These results suggest that Ras, along with the activation of additional pathways, is required for the generation of G1 CDK activity, and that activation of cyclin E-dependent kinase in particular depends on the cooperative action of Ras and Myc.

Animals↗