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Biomedical subjects

G Leone

Publications and source records attributed to G Leone.

At least 19 recordsLinked to original sources
PubMed1992

The reovirus cell attachment protein possesses two independently active trimerization domains: basis of dominant negative effects.

The reovirus cell attachment protein, sigma 1, is a homotrimer with an N-terminal fibrous tail and a C-terminal globular head. By cotranslating full-length and various truncated sigma 1 proteins in vitro, we show that the N- and C-terminal halves of sigma 1 possess independent trimerization and folding domains. Trimerization of sigma 1 is initiated at the N-terminus by the formation of a "loose," protease-sensitive, three-stranded, alpha-helical coiled coil. This serves to bring the three unfolded C-termini into close proximity to one another, facilitating their subsequent trimerization and cooperative folding. Concomitant with, but independent of, this latter process, the N-terminal fiber further matures into a more stable and protease-resistant structure. The coordinated folding of sigma 1 trimers exemplifies the dominant negative effects of mutant subunits in oligomeric complexes.

Capsid Proteins↗
PubMed1992

Hematological causes of venous thrombosis in young people: high incidence of myeloproliferative disorder as underlying disease in patients with splanchnic venous thrombosis.

Thrombotic events occur frequently in myeloproliferative disorders, namely polycythaemia vera and essential thrombocythaemia. Standard diagnostic criteria are designed quite stringent, so that a number of patients could be underdiagnosed. Spontaneous erythroid colonies formation from bone marrow or peripheral blood in the absence of exogenous erythropoietin is considered a reliable index of myeloproliferative disorder even at early stages. Endogenous erythroid colonies (EECs) formation was assessed in 43 patients having recently suffered from venous thrombosis prior to 45 years and without a previous diagnosis of hematological disease favouring thrombosis. A screening for coagulative abnormalities associated with thrombophilia was also carried out: in 5 patients (11.6%) a plasmatic thrombogenic defect was found (quantitative deficiency of antithrombin III, 1 case, protein C, 2 cases, protein S, 1 case, and plasminogen, 1 case). In 10 patients (2 males and 8 females) (23.2%) EECs assay was positive, allowing diagnosis of myeloproliferative disease even though 7 of them did not fulfill standard diagnostic criteria. In the other 3 patients who met the criteria for diagnosis of overt myeloproliferative disease the thrombotic event was the inaugural manifestation. In all these EECs-positive patients thrombosis involved mesenteric and portal veins (n = 4), hepatic veins (n = 3), portal vein (n = 2), mesenteric vein (n = 1). One of them was simultaneously affected from congenital protein C deficiency. Thus latent or atypical forms of myeloproliferative disease as well as the overt stages were the most frequent recognized cause of splanchnic venous thrombosis, accounting for 55% of the cases of our series. On the contrary no EECs-positive subject was found among the 25 patients with other sites of thrombosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Effects of a preformed extracellular matrix on long-term serum-free bone marrow culture.

The extracellular matrix (ECM) produced by the stromal layer plays a key role in the regulation of commitment and differentiation of hematopoietic cells. Long-term bone marrow culture (LTBMC) allows analysis of the stromal microenvironment. Recently, serum-free LTBMC has been described, but the formation of a classical adherent layer was never observed under these conditions. We have evaluated the effect(s) of a chemically well defined ECM on serum-free and serum-dependent LTBMC. In serum-dependent cultures ECM did not induce a significant increase of hematopoiesis. In serum-free conditions, a marked improvement of hematopoiesis was observed, both in terms of CFU-GM and BFU-E yield and in duration of cultures. A confluent stromal layer was observed only in the presence of ECM. The present results indicate that the addition of ECM to serum-free cultures provides a standardized culture condition, while improving progenitor cell recovery and allowing formation of a confluent stromal layer. Moreover, ECM+LTBMC may provide a model to study the effect(s) of adhesive proteins and hematopoietic growth factors normally present in serum.

Blood↗
PubMed1992

Describing and interpreting 24-hour blood pressure patterns in physiologic pregnancy.

The time course of blood pressure in clinically healthy (pregnant and nonpregnant) women was followed by automatic ambulatory monitoring. Chronobiologic methods revealed the time course of dynamic rhythm characteristics as a function of gestational age. Differences were found between nonpregnant and pregnant women with an overall lowering during pregnancy of the rhythm-adjusted midline estimating statistic of rhythm (mesor).

Blood Pressure↗
PubMed1992

The combination of quercetin and cytosine arabinoside synergistically inhibits leukemic cell growth.

It has been demonstrated that quercetin (3,3',4',5,7-pentahydroxyflavone) inhibits the growth of several cancer cell lines and that the antiproliferative activity of this substance is probably mediated through a binding interaction with type II estrogen binding sites (type II EBS). The effect of quercetin and cytosine arabinoside (Ara-C) alone or in combination, was tested on HL-60 cell growth. Quercetin significantly synergized the inhibitory activity of Ara-C on HL-60 cell growth while rutin, the 3-rhamnosylglucoside of quercetin, neither competed with [3H]estradiol for type II EBS nor was effective alone or in combination with Ara-C. Based on these results, we studied by a clonogenic assay the effect of quercetin and Ara-C alone and in combination on colony formation by human leukemic cells (CFU-L). In all cases both drugs exhibited a dose-related inhibition of CFU-L in a range of concentrations between 10 nM and 10 microM and 0.01 nM and 10 microM for quercetin and Ara-C, respectively. The combination of the two drugs resulted in a synergistic inhibitory activity on CFU-L. Considering that plasma concentrations of quercetin effective in vitro were obtained in vivo without any apparent side effects, we conclude that this report represents further experimental evidence that quercetin could be used in the treatment of acute leukemias.

Acute Disease↗
PubMed1992

Incidence of thrombotic complications in adult patients with acute lymphoblastic leukaemia receiving L-asparaginase during induction therapy: a retrospective study. The GIMEMA Group.

The incidence of thrombotic complications chronologically related to L-asparaginase administration is retrospectively analyzed in 238 adult ALL patients treated according to the GIMEMA protocol ALL 0288. The patients (126 males and 112 females, aged 12-68 years, median 29) received E. coli L-asparaginase (L-ase) in the induction phase at a dosage of 6000 U/m2/day x 7 d starting on d 15, as well as vincristine, prednisone, daunorubicin and cyclophosphamide, the last-named by random 1:1. Ten patients (4.2%) developed thrombotic complications 5-15 d (median 11 d) after the start of L-ase treatment. The thrombotic events, which were lethal in 5 patients, involved the cerebral sinus (5 cases), the cerebral arteria (2 cases), the portal vein (1 case), the pulmonary district (1 case), and a deep vein in the lower extremity (1 case). The occurrence of these complications was not related to the general thrombotic risk factors, nor to the main clinical and laboratory data registered at diagnosis and immediately before the start of L-asparaginase treatment. The present study documents for the first time in a sufficiently large series of adult ALL patients that the incidence and the severity of thrombotic events related to L-ase administration are relevant and need further consideration.

Adolescent↗
PubMed1992

Aggressive chemotherapy for acute leukemia relapsed after bone marrow transplantation: a second chance?

Eight patients, 5 with acute non lymphoid leukemia and 3 with lymphoid leukemia, were treated at relapse after bone marrow transplantation (BMT; 4 autologous BMT and 4 allogeneic BMT). Of these, 2 relapsed within 3 months after BMT (2 allogeneic BMT) and 6 (2 allogeneic and 4 autologous BMT) after more than 9 months after BMT. The 2 patients relapsing early showed no response to treatment and died. Five out of 6 patients relapsing late achieved complete remission (4 of them with intensive chemotherapy). Four patients are currently alive. Aggressive combination chemotherapy can produce long-term survival in selected patients relapsed after BMT.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Nocturnal headache-hypertension syndrome: a chronobiologic disorder.

The study of blood pressure (BP) monitoring in essential hypertensive patients recurrently suffering from nocturnal headache revealed a rhythmic elevation of sphygmomanometric values during the night. Such a finding was not detected in essential hypertensive patients suffering from occasional headache. The nocturnal elevation of BP was seen to be paralleled by the circadian peak of heart rate, suggesting that the disorder is a systemic phenomenon. Importantly, the headache episodes were seen to disappear after antihypertensive therapy that was adjusted to lower the nocturnal increase of BP. The therapeutic results suggested that the nocturnal headache was dependent on the phasic elevation of BP. The beneficial effects further suggested that the nocturnal headache and the nocturnal elevation of BP may represent a particular syndrome with a cause-effect relationship. The term "nocturnal headache-hypertension syndrome" is proposed.

Adolescent↗
PubMed1992

[A 24-hour blood pressure and heart rate pattern in healthy persons over 70 years of age. A Campodimele study].

The present report is aimed at studying the 24-h pattern of blood pressure in elderly subjects (45 men and 47 women, aged from 76 to 102 years), recruited in Campodimele, a small city where the population of ultra septuagenaries is very dense. The investigation has been performed by mean of ambulatory non-invasive monitoring combined with chronobiometric estimates. The computation has been performed on raw data, rhythmic series and integral profiles. The analysis has been stratified according to sex. The tabulated estimates constitute an index of reference for blood pressure 24-h pattern in aged people.

Aged↗
PubMed1991

Vasoactive intestinal peptide fluctuates in human blood with a circadian rhythm.

The vasoactive intestinal peptide (VIP) may be radioimmunoassayed in systemic venous blood. The plasma concentrations of VIP were investigated in human blood according to a chronobiological design. The study documented a circadian rhythmicity in time-qualified concentrations of VIP. Accordingly, VIP may be ascribed to biological variables characterized by periodicity in their physiological attributes. The rhythmic physiology of VIP is, however, highly disturbed in its tonic and phasic properties during senescence.

Adult↗