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Biomedical subjects

G Leone

Publications and source records attributed to G Leone.

At least 163 records · Page 9Linked to original sources
PubMed1998

Different risks of thrombosis in four coagulation defects associated with inherited thrombophilia: a study of 150 families.

Deficiency of the naturally occurring anticoagulant proteins, such as antithrombin, protein C and protein S, and activated protein C resistance due to the factor V Leiden gene mutation is associated with inherited thrombophilia. So far, no direct comparison of the thrombotic risk associated with these genetic defects is available. In this study, we wish to compare the lifetime probability of developing thrombosis, the type of thrombotic symptoms, and the role of circumstantial triggering factors in 723 first- and second-degree relatives of 150 index patients with different thrombophilic defects. We found higher risks for thrombosis for subjects with antithrombin (risk ratio 8.1, 95% confidence interval [CI], 3.4 to 19.6), protein C (7.3, 95% CI, 2.9 to 18.4) or protein S deficiency (8.5, 95% CI, 3. 5 to 20.8), and factor V Leiden (2.2, 95% CI, 1.1 to 4.7) than for individuals with normal coagulation. The risk of thrombosis for subjects with factor V Leiden was lower than that for those with all three other coagulation defects (0.3, 95% CI, 0.1 to 1.6), even when arterial and superficial vein thromboses were excluded and the analysis was restricted to deep vein thrombosis (0.3, 95% CI, 0.2 to 0.5). No association between coagulation defects and arterial thrombosis was found. The most frequent venous thrombotic manifestation was deep vein thrombosis with or without pulmonary embolism (90% in antithrombin, 88% in protein C, 100% in protein S deficiency, and 57% in factor V Leiden), but a relatively mild manifestation such as superficial vein thrombosis was common in factor V Leiden (43%). There was a predisposing factor at the time of venous thromboembolism in approximately 50% of cases for each of the four defects. In conclusion, factor V Leiden is associated with a relatively small risk of thrombosis, lower than that for antithrombin, protein C, or protein S deficiency. In addition, individuals with factor V Leiden develop less severe thrombotic manifestations, such as superficial vein thrombosis.

Adolescent↗
PubMed1998

E2F3 activity is regulated during the cell cycle and is required for the induction of S phase.

Previous work has demonstrated the important role of E2F transcription activity in the induction of S phase during the transition from quiescence to proliferation. In addition to the E2F-dependent activation of a number of genes encoding DNA replication activities such as DNA Pol alpha, we now show that the majority of genes encoding initiation proteins, including Cdc6 and the Mcm proteins, are activated following the stimulation of cell growth and are regulated by E2F. The transcription of a subset of these genes, which includes Cdc6, cyclin E, and cdk2, is also regulated during the cell cycle. Moreover, whereas overall E2F DNA-binding activity accumulates during the initial G1 following a growth stimulus, only E2F3-binding activity reaccumulates at subsequent G1/S transitions, coincident with the expression of the cell-cycle-regulated subset of E2F-target genes. Finally, we show that immunodepletion of E2F3 activity inhibits the induction of S phase in proliferating cells. We propose that E2F3 activity plays an important role during the cell cycle of proliferating cells, controlling the expression of genes whose products are rate limiting for initiation of DNA replication, thereby imparting a more dramatic control of entry into S phase than would otherwise be achieved by post-transcriptional control alone.

CDC2-CDC28 Kinases↗
PubMed1998

Prothrombin G20210A mutant genotype is a risk factor for cerebrovascular ischemic disease in young patients.

The factor II G20210A mutation is a recently identified congenital risk factor for venous thrombosis. Its role in artery disease is still undefined. We investigated 72 patients (35 male and 37 female) with documented ischemic stroke occurred before 50 years of age and without risk factors such as diabetes, hypertension, and hyperlipidemia; 198 thrombosis-free individuals were investigated as the control group. We found 7 heterozygotes (9.7%) and 2 homozygotes (2.7%) for the mutant factor II allele among the patients and 5 heterozygotes (2.5%) among the controls; the mutant factor II allele frequency in the patient group (7.6%, 95% confidence interval [CI], 3.3 to 11.9) was significantly higher than in the controls (1.2%; 95% CI, 0.1 to 2.3; P = .0001). The prevalence of other investigated mutant alleles (factor V G1691A, methylenetetrahydrofolate reductase C677T) did not significantly differ between the two groups. The odds ratio for ischemic stroke associated with the carriership of the mutant factor II allele (both heterozygous and homozygous genotypes) was 5.1 (95% CI, 1.6 to 16.3). Heterozygous genotype was associated with a 3.8-fold increased risk for cerebral ischemia (95% CI, 1.1 to 13.1); in particular, assuming an expected prevalence of homozygotes in the general population of 1.6 to 10,000 according to the Hardy-Weinberg equilibrium, the risk associated with the homozygous genotype was estimated exceedingly high, being increased 208-fold.

Adolescent↗
PubMed1998

Molecular beacon probes combined with amplification by NASBA enable homogeneous, real-time detection of RNA.

Molecular beacon probes can be employed in a NASBA amplicon detection system to generate a specific fluorescent signal concomitantly with amplification. A molecular beacon, designed to hybridize within the target sequence, was introduced into NASBA reactions that amplify the genomic RNA of potato leafroll virus (PLRV). During amplification, the probe anneals to the antisense RNA amplicon generated by NASBA, producing a specific fluorescent signal that can be monitored in real-time. The assay is rapid, sensitive and specific. As RNA amplification and detection can be carried out in unopened vessels, it minimizes the risk of carry-over contaminations. Robustness has been verified on real-world samples. This homogeneous assay, called AmpliDet RNA, is a significant improvement over current detection methods for NASBA amplicons and is suitable for one-tube applications ranging from high-throughput diagnostics to in vivo studies of biological activities.

Base Sequence↗
PubMed1998

Cdc6 is regulated by E2F and is essential for DNA replication in mammalian cells.

Cdc6 has a critical regulatory role in the initiation of DNA replication in yeasts, but its function in mammalian cells has not been characterized. We show here that Cdc6 is expressed selectively in proliferating but not quiescent mammalian cells, both in culture and within tissues of intact animals. During the transition from a growth-arrested to a proliferative state, transcription of mammalian Cdc6 is regulated by E2F proteins, as revealed by a functional analysis of the human Cdc6 promoter and by the ability of exogenously expressed E2F proteins to stimulate the endogenous Cdc6 gene. Immunodepletion of Cdc6 by microinjection of anti-Cdc6 antibody blocks initiation of DNA replication in a human tumor cell line. We conclude that expression of human Cdc6 is regulated in response to mitogenic signals though transcriptional control mechanisms involving E2F proteins, and that Cdc6 is required for initiation of DNA replication in mammalian cells.

Animals↗
PubMed1998

Acute myeloid leukemia after iodine-131 treatment for thyroid disorders.

Leukemia has rarely been reported as a late complication of 131I therapy, occurring mostly after cumulative doses of 800 mCi. We observed two cases of acute myeloid leukemia (AML) after 131I therapy for hyperthyroidism and thyroid carcinoma, respectively. The first patient was a 45-year-old woman treated with a single dose of 27 mCi 131I for hyperthyroidism. She developed AML (FAB M2) 14 months after receiving 131I; the second patient was a 44-year-old man affected by refractory thyroid carcinoma who received a total dose of 1 Ci 131I plus radiotherapy and developed AML (FAB M6) 8 years after the first exposure to 131I. Although it is a very rare event, the occurrence of leukemia after 131I treatment should be kept in mind, considering the widespread use of 131I, particularly in the treatment of hyperthyroidism, and the unfavorable outcome of secondary leukemia.

Acute Disease↗
PubMed1998

The effect of gravity on human recognition of disoriented objects.

The role of non-visual cues, and particularly of signals tied to the direction of gravity, in the mechanisms of recognition of disoriented objects is reviewed. In spite of a limited number of studies, object recognition does not seem dramatically altered by weightlessness and astronauts can adapt to this novel environment. Particularly, mental rotation strategy can still be used in weightlessness with dynamic parameters relatively unchanged. Similarly, spatial coordinate assignment can be performed adequately under different gravitational conditions. However, signals related to gravity direction seem to be integrated in the early stages of visual processing. Thus, performances in symmetry detection tasks and visual search tasks are influenced by the gravito-inertial conditions in which experience are done. Functional roles of such a multisensory convergence on cortical visual neurons, partly confirmed by neurophysiological studies, are proposed.

Form Perception↗
PubMed1998

Flow cytometric detection of perforin in normal human lymphocyte subpopulations defined by expression of activation/differentiation antigens.

We investigated with three-color flow cytometry the expression of perforin (Pf) in normal human lymphocyte subpopulations identified by means of activation and differentiation-related antigens. Interestingly, Pf could be detected in a substantial subset (13 +/- 2%) of memory CD4+ CD45RO+ cells, on relevant percentages of memory (CD45RO+) and naive (CD45RA+) CD8+ cells and on virtually all CD3- CD16+, CD3- CD56+ and NKB1+ natural killer cells, as expected. The analysis of fluorescence intensity showed higher levels of Pf expression on CD8dim and NK cells compared to CD8bright and CD4+ lymphocytes, Pf and CD69, HLA-DR, CD95 and CD25 activation/differentiation-related antigens were never co-expressed. On average, 15 +/- 3% of CD3+ CD28+ cells were found to be Pf+, in line with a previously activated or memory cell type. Comparable percentages of CD8+ CD11b- (cytotoxic) and CD8+ CD11b+ (suppressor) T cells were Pf+. Multiparameter flow cytometry is a powerful tool to detect minute fractions of Pf-expressing cells in heterogeneous populations.

Biomarkers↗
PubMed1998

Temporal control and motor control: two functional modules which may be influenced differently under microgravity.

Three subjects performed sequences of periodic movements by synchronizing their movements (button pressing with the thumb) to a series of visual stimuli (induction phase), and by continuing to produce the movements with the same rhythm after the metronome had been switched off (continuation phase). The required inter-response intervals (IRIs) were 450, 550 or 650 ms. Two subjects were members of the EUROMIR 94 spaceflight mission. The inter-response intervals of the continuation phase were analyzed in terms of mean and variability. The mean inter-response intervals did not differ systematically during spaceflight from the pre- and post-flight values. The variability of the inter-response intervals significantly increased during the flight with both experimental subjects. The total variance of the inter-response intervals was partitioned into variance due to the internal timekeeper and variance due to the motor implementation processes, following the method proposed by Wing, A.M., Kristofferson, A.B., 1973. Response delays in the timing of discrete motor responses. Perception and Psychophysics 14, 5-12. The variance attributed to the timekeeper showed a significant increase with both subjects, whereas the variance attributed to the motor processes showed inconsistent trends during the spaceflight. It is concluded that during spaceflight, the functioning of the internal timing module may undergo some changes, as the result of which the regularity of the motor timing is slightly impaired.

Adult↗
PubMed1998

In vitro effect of amifostine on haematopoietic progenitors exposed to carboplatin and non-alkylating antineoplastic drugs: haematoprotection acts as a drug-specific progenitor rescue.

We evaluated the protective ability of amifostine on peripheral blood mononuclear cell (PBMC)-derived colony-forming unit (CFU) and PB CD34+ cells which were previously exposed in vitro to etoposide, carboplatin, doxorubicin and taxotere. Amifostine pretreatment protected PBMC-derived CFU from the toxic effect of etoposide, carboplatin and taxotere. A significant detrimental effect was exerted by amifostine on the growth of doxorubicin-treated PBMC-derived CFU. Liquid cultures of PB CD34+ cells reproduced faithfully the effects observed on growth of PBMC-derived CFU and confirmed amifostine chemoprotection against etoposide and carboplatin with its detrimental effect on doxorubicin-treated progenitors. Combining the data of viable cell count, cytometric estimation of apoptosis, cell cycle and viable cell replication rate, we found that amifostine protects from etoposide and carboplatin toxicity mainly through a mechanism of cell rescue. Conversely, the detrimental effect of amifostine on the growth of doxorubicin-treated PB CD34+ cells is apparently due to an increased G2/M arrest. In conclusion, amifostine protects haematopoietic progenitors from etoposide, carboplatin and taxotere. Progenitor rescue is the mechanism through which amifostine reduced etoposide and carboplatin toxicity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Highly fluorescent reticulocytes after CD34+ peripheral blood progenitor cell transplantation.

Highly fluorescent reticulocyte (HFR) counts were evaluated in 13 consecutive patients affected by hematological malignancies and submitted to autologous selected CD34+ peripheral blood progenitor cell (PBPC) transplantation. Results were compared with a historical group of patients comparable for age, disease and conditioning regimen submitted to unfractionated PBPC transplantation. HFR counts of the CD34+ group declined to an undetectable level from day +4 to day +10 when they became detectable and reached 5% of total reticulocyte count by day +12. In the historical group, the nadir was identical but the recovery was faster (day +9). Total reticulocyte count > 1% was achieved at days +17 and +11, respectively. The absolute neutrophil count (ANC) recovery was identical in both groups, achieving a value > 0.5 x 10(9)/l at day +13 after reinfusion. Hence, in the historical group, HFR count gave advance notice of complete and stable hemopoietic engraftment while in the CD34+ group HFR and ANC count showed almost simultaneous recovery.

Adult↗
PubMed1998

Luteinizing hormone-releasing hormone analogue: leuprorelin acetate for the prevention of menstrual bleeding in premenopausal women undergoing stem cell transplantation.

Prevention of uterine bleeding after stem cell transplantation was attempted in 30 consecutive premenopausal women affected by hematological malignancies. This was with luteinizing hormone-releasing hormone (LHRH) leuprorelin acetate depot 3.75 mg administered subcutaneously at least 30 days before the conditioning regimen and then 28 days after the first dose. Complete prevention resulted in all but one patient (96.5%) during the phase of profound thrombocytopenia. No side-effects related to leuprorelin were observed. All patients developed amenorrhea after transplantation. Gonadal function was periodically assessed by means of luteinizing hormone (LH), follicular stimulating hormone (FSH) and estradiol serum levels. Hormone levels were consistent with menopause in all patients. After transplantation, patients required hormone replacement with estroprogestinics or estrogens alone when indicated. Leuprorelin is highly effective in preventing uterine bleeding in premenopausal women undergoing stem cell transplantation and has an excellent toxicity profile and virtually no interface with hemostatic balance and hepatic function. The role of leuprorelin in gonadal protection is currently unclear and deserves further investigations.

Adolescent↗
PubMed1998

Long-lasting complete remission in plasma cell leukemia after aggressive chemotherapy and CD34-selected autologous peripheral blood progenitor cell transplant: molecular follow-up of minimal residual disease.

Plasma cell leukemia is a rare disease associated with very poor survival with standard treatment. We report a patient affected by plasma cell leukemia treated with aggressive chemotherapy and autologous CD34-selected PBPC who achieved a complete remission now lasting more than 2 years. Molecular studies confirmed the presence of minimal residual disease (MRD) despite the absence of disease activity. High-dose chemotherapy with stem cell rescue may be applied to selected patients considering the impact of the treatment on survival. The meaning of molecular MRD in this setting is unclear.

Antigens, CD34↗
PubMed1998

Secondary haematological neoplasm after treatment of adult acute lymphoblastic leukemia: analysis of 1170 adult ALL patients enrolled in the GIMEMA trials. Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto.

Between 1983 and 1994 the incidence of secondary haematological neoplasms (SHM) was evaluated in 1170 new cases of ALL enrolled in the GIMEMA trials. Of the 942 patients who achieved complete remission (CR); seven developed a SHM: four AMLs and three NHLs. The median latency from onset of ALL and of secondary haematological neoplasm was 69 months for AML and 61 months for NHL. Three out of four patients with secondary AML were unresponsive to the new chemotherapy and died, whereas the fourth patient achieved a new CR. Among the three NHL cases, two patients are presently alive in CR, whereas the third patient was refractory to chemotherapy and died. The relative risk of haematological malignancy among the GIMEMA trials population, as compared to that of the Italian Cancer Registries, was 15.25-fold higher, and the actuarial estimated cumulative proportion of ALL patients with a secondary haematological neoplasm at 5 and 10 years were 0.59% and 3.63% respectively. The incidence of adult ALL who developed a SHM, although apparently lower than in the paediatric ALL series, was higher when compared to the normal population. The difference between paediatric and adult ALL is probably due to the lack of craniospinal radiotherapy and to the lower doses of epipodoxiphyllotoxins used in adult trials. The higher percentage of childhood ALL with a prolonged event-free survival could result in an increase of secondary neoplasms in these cases, which suggests that secondary haematological neoplasms in adult ALL patients are real, although rare, events.

Adolescent↗
PubMed1998

Functional, phenotypic and molecular characterization of cytokine low-responding circulating CD34+ haemopoietic progenitors.

Circulating CD34+ cell populations characterized by a low rate (up to five) or high rate (more than five) of cell divisions were isolated from 8 d cultures in the presence of stem cell factor (SCF), interleukin-3 (IL-3), granulocyte-macrophage colony stimulating factor (GM-CSF), granulocyte colony stimulating factor (G-CSF), erythropoietin (EPO), Flt3 ligand and Peg-rHu megakaryocyte growth and development factor (Peg-rHuMGDF) using the fluorescent dye 5,6-carboxyfluorescein diacetate succinimidyl ester (CFDA-SE) and flow cytometric cell sorting. Phenotypic characterization of cells which had experienced up to five divisions (CFDA-SEbright) showed a similar surface antigen expression to starting, freshly isolated CD34+ cells. Conversely, cells which experienced more than five divisions (CFDA-SEdim) showed a differentiating behaviour, down-regulating CD34 antigen and acquiring differentiation markers. CFDA-SEbright cells were significantly enriched in CD105 (endoglin) positive precursors as compared to both freshly isolated CD34+ and CFDA-SEdim cells. Functional analysis indicated that CFDA-SEbright had a 3-fold and 10-fold greater cumulative cloning efficiency as compared to freshly isolated CD34+ cells and CFDA-SEdim cells, respectively. CFDA-SEbright cells retained the vast majority of LTC-IC and showed a LTC-IC frequency 2.8-fold higher than that found in freshly isolated CD34+ cells. RT-PCR and Western blot analyses showed significantly higher bcl-2 RNA and protein levels in CFDA-SEbright cells as compared to freshly isolated CD34+ and CFDA-SEdim cells. This study indicates that cytokine low-responding circulating CD34+ cells (CFDA-SEbright cells) represent a functionally, phenotypically and molecularly distinct multipotent progenitor population with biological properties associated with primitive precursors.

Antigens, CD↗