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G Migliaccio

Publications and source records attributed to G Migliaccio.

118 records · Page 7Linked to original sources
PubMed1979

Early fluctuations of BFU-E pool size after transfusion or erythropoietin treatment.

The kinetics of erythroid burst-(BFU-E) and colony-forming units (CFU-E) have been evaluated in marrow and spleen of normal or polycythemic mice, respectively, after transfusion or administration or purified erythropoietin (Ep). Ep injection induces an early but temporary rise of BFU-E number, versus a later but more prolonged expansion of the CFU-E pool. Symmetric patterns are observed after transfusion, i.e., an early but transient depletion of the BFU-E population, versus a later but more persistent decrease of the CFU-E number. It is suggested that the size of the BFU-E compartment is Ep-dependent in the "early" phase after erythroid perturbation. Later on, however, compensatory mechanisms allow the BFU-E pool to "escape" from the early Ep influence, thus allowing its size to return to and stabilize in the near normal range. It is further suggested that the BFU-E may represent an early target cell of Ep stimulus.

Animals↗
PubMedDate not supplied

Haemoglobin switching in human embryos: asynchrony of zeta----alpha and epsilon----gamma-globin switches in primitive and definite erythropoietic lineage.

Haemoglobin switching in humans provides a unique model for investigating the mechanisms underlying expression of a developmentally regulated gene family. Numerous studies have focused on the switch from fetal to adult (that is, gamma----beta) globin, but little is known about the embryonic----fetal (that is, zeta----alpha and epsilon----gamma) switches, as well as the transition from 'primitive' yolk sac to 'definitive' liver erythropoiesis. Here we have studied the embryonic----fetal haemoglobin switches in yolk sac, liver and circulating blood erythroblasts from 25 embryos and 6 fetuses. Globin synthesis was also evaluated in purified 'primitive' and 'definitive' erythroblasts. Primitive erythroblasts synthesize essentially zeta and epsilon chains at 5 weeks and alpha- and epsilon-globin with a minor aliquot of zeta and gamma chains at 6-7 weeks, whereas definitive erythroblasts produce alpha and epsilon + gamma + beta-globin at 6 weeks but only alpha and gamma + beta chains from 8 weeks onward. In both lineages the zeta----alpha and the epsilon----gamma switches are asynchronous, the former preceding the latter. Furthermore, zeta- and beta-globin synthesis is restricted to primitive and definitive erythroblasts respectively. These findings are discussed in terms of a monoclonal model for haemoglobin switching in early human ontogeny.

Age Factors↗
PubMedDate not supplied

Preclinical pharmacokinetics and metabolism of a potent non-nucleoside inhibitor of the hepatitis C virus NS5B polymerase.

The disposition of compound A, a potent inhibitor of the hepatitis C virus (HCV) NS5B polymerase, was characterized in animals in support of its selection for further development. Compound A exhibited marked species differences in pharmacokinetics. Plasma clearance was 44 ml min-1 kg-1 in rats, 9 ml min-1 kg-1 in dogs and 16 ml min-1 kg-1 in rhesus monkeys. Oral bioavailability was low in rats (10%) but significantly higher in dogs (52%) and monkeys (26%). Compound A was eliminated primarily by metabolism in rats, with biliary excretion accounting for 30% of its clearance. Metabolism was mainly mediated by cyclohexyl hydroxylation, with N-deethylation and acyl glucuronide formation constituting minor metabolic pathways. Qualitatively, the same metabolites were identified using in vitro systems from all species studied, including humans. The low oral bioavailability of compound A in rats was mostly due to poor intestinal absorption. This conclusion was borne out by the findings that hepatic extraction in the rat was only 30%, intraperitoneal bioavailability was good, and compound A was poorly absorbed from the rat isolated intestinal loop, with no detectable intestinal metabolism. Compound A was not an inhibitor of major human cytochrome P450 enzymes, indicating minimal potential for clinical drug-drug interactions. The metabolic clearance of compound A in rat, dog and monkey hepatocytes correlated with the systemic clearance observed in these species. Since compound A was very stable in human hepatocytes, the results suggest that it will be a low clearance drug in humans.

Animals↗
PubMedDate not supplied

Circulating hematopoietic stem cell populations in human fetuses: implications for fetal gene therapy and alterations with in utero red cell transfusion.

Circulating progenitor cell populations in normal human fetuses and fetuses with various hematological problems were evaluated. Thirty blood samples from 21 human fetuses (17-36 weeks of gestation) were assayed for erythroid, myeloid, and mixed-cell progenitor cells. The mean number of progenitor cells/10(4) blood mononuclear cells in the normal fetal population was 103 +/- 47. Granulomonocytic and mixed progenitor cells (capable of giving rise to both erythroid and myeloid progeny) were the predominant progenitor types in these samples, with pure erythroid progenitors barely detectable. The frequency of progenitor cells in the samples from fetuses with hematological disorders was within the range of normal in all but 1 fetus infected with parvovirus in whom very few progenitor cells were detected. The frequency of progenitor cells in the blood did not change after intravascular red cell transfusion for alloimmunization despite the large volumes transfused, indicating that transfusion may have triggered a release of progenitor cells into the circulation. Progenitor cells in human fetal blood are present in distributions similar to those commonly detected in cord blood. Their total number in the circulating blood is in the same order used for pediatric and adult bone marrow transplantation. These results can be used to calculate the number of colony-forming cells which could be obtained from a fetus by in utero apheresis and which could be made available for autologous fetal gene therapy.

Antigens, CD34↗
PubMedDate not supplied

[Experimental study on efficacy of thermal muds of Ischia Island combined with balneotherapy in the treatment of psoriasis vulgaris with plaques].

A lot of studies show the efficacy of thermal therapy in psoriasis. The main indications concern all forms of psoriasis (except for pustolosa and eritrodermic) especially diffuse psoriasis, intensive itchy, artropatic psoriasis and gutted psoriasis child. Benefit effects of thermal water and muds, which are important parameters in psoriasis' treatment, they are excellent to reduce inflammation, scaling, and erythema. In this study we evaluated the clinical efficacy of thermal bath plus muds in patients affected by psoriasis. 18 patients has been examined and randomly divided in 3 group (A-B-C). All the patients received thermal therapy for 4 weeks. To evaluate the behaviour of the disease we performed (corneometry, sebometry, phmetry), as well as evaluation of P.A.S.I. At the end of the study, values of P.A.S.I. showed a reduction from 10 to 6 unites P.A.S.I. for patients belong to group A, more 12 to less 10 for patients belong to group C e no significant variations for group B (because represent control group). Results obtained can be considered useful, considering that thermal treatment was used alone in the treatment of all patients.

Adult↗
PubMedDate not supplied

Direct effects of IL-4 on the in vitro differentiation and proliferation of hematopoietic progenitor cells.

The purpose of this study was to analyze the effects of recombinant human interleukin 4 (IL-4) on the differentiation and proliferation in vitro of human granulocyte/macrophage (GM) and erythroid progenitors. IL-4 was added to either fetal bovine serum (FBS)-supplemented or to FBS-deprived cultures of unfractionated human marrow cells or marrow cells depleted of adherent and/or T cells. Paradoxical effects similar to those reported in the murine system were detected in these experiments. In FBS-supplemented cultures, IL-4, which had no effect on the growth or erythroid bursts (from burst-forming cells; BFU-E) detected in the presence of Epo alone, decreased by 46% the number of erythroid bursts detected in the presence of Epo and phytohemagglutinin-stimulated leukocyte-conditioned medium (PHA-LCM). In contrast, in FBS-deprived cultures, IL-4 increased by 30-700% the number of erythroid bursts in cultures containing Epo alone or containing Epo, IL-3, and GM-CSF. The stimulatory effect of IL-4 on erythroid burst growth under FBS-deprived conditions was particularly evident when adherent cells were removed. Under the conditions investigated, IL-4 had little effect on the growth of GM colonies. In FBS-deprived suspension cultures of nonadherent, T-cell-depleted marrow cells, IL-4 maintained both the number of BFU-E and CFU-GM for at least 8 days. In these cultures, IL-4 antagonized the capacity of IL-3 to increase the number of BFU-E but IL-4 and IL-3 acted together to maintain the number of CFU-GM. To determine if IL-4 acted directly or indirectly, its effects on the growth of factor-dependent subclones of the murine progenitor cell line 32D were analyzed. Three subclones were studied: the original IL-3-dependent clone 32D cl.3, the Epo-dependent erythroid clone 32D Epo-1, and the G-CSF-dependent myeloid clone 32D G-1. IL-4 alone failed to induce colony growth from these cell lines. However, IL-4 inhibited by 25% the number of colonies formed by 32D cl.3 in the presence of IL-3 while increasing by 25% and 25-50% the number of colonies formed by 32D Epo-1 and 32D G-1 in the presence of Epo or G-CSF, respectively. These results indicate that human IL-4, as its murine counterpart, is a multilineage growth factor with paradoxical effects which are mediated by the direct action of IL-4 on progenitor cells.

Cell Differentiation↗