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Biomedical subjects

G Salvo

Publications and source records attributed to G Salvo.

21 records · Page 2Linked to original sources

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↗

Long-term culture growth of CD4-CD8- lymphocytes exhibiting elevated non-MHC-restricted cytotoxic activity.

We have developed a culture system for "long-term" growth of human lymphokine-activated killer (LAK) cells exhibiting an elevated, wide-spectrum anti-tumor cytotoxicity. The system allows the exponential growth of monocyte- and B-lymphocyte-depleted CD4-CD8- lymphocytes in the presence of human AB serum and recombinant human interleukin-2 (IL-2) (2 x 10(2) U/ml) combined with interleukin (IL-1) beta (50 ng/ml). After 21 days in culture, these cells undergo massive amplification (i.e., the cell yield rises up to 30-120 times the starting values), and exhibit a marked anti-tumor cytotoxic activity against a panel of natural killer (NK)-resistant tumor cell lines. Interestingly, this activity correlates with the high level of perforin RNA. The membrane phenotypes of the final cell population, assessed by a panel of monoclonal antibodies (MoAbs) indicate a mixed population comprising two cell types in variable proportions (i) NKH-1+, T cell receptor (TCR) alpha/beta-, TCR gamma/delta-, CD3-, Leu 23+; (ii) NKH-(+), TCR alpha/beta-, TCR gamma/delta+, CD3+, Leu 23+. This culture system may provide a tool for cellular and molecular studies on the mechanisms of anti-tumor cytotoxicity, as well as the basis for new adoptive immunotherapy protocols in advanced cancers.

Antigens, CD↗

Effects of oral and intravenous defibrotide on blood viscosity in patients with peripheral obliterative arterial disease.

Patients with peripheral obliterative arterial disease received 400 mg of defibrotide intravenously (seven patients) or orally (nine patients). Blood and plasma viscosity were measured before therapy, at 30 minutes after and one hour after intravenous administration, and at 1, 2, 3, and 8 hours after oral administration. Thirty minutes after intravenous administration, blood viscosity at a shear rate of 30 sec-1 was reduced from 9.99 to 9.00 and at a shear rate of 180 sec-1 from 6.61 to 6.33 (P less than 0.05). Viscosity returned to baseline after 60 minutes. At 1, 2, and 3 hours after oral administration, blood viscosity at a shear rate of 30 sec-1 was reduced from 8.53 to 7.44, 6.88, and 7.19 (each P less than 0.01) and at a shear rate of 180 sec-1 from 5.88 to 5.51 (P less than 0.05), 5.14 (P less than 0.05), and 5.38 (P less than 0.01); the levels at eight hours were not significantly different from baseline values. Plasma viscosity was not affected by defibrotide. These data confirm previous evidence of a rheologic effect of defibrotide in patients with peripheral obliterative arterial disease and indicate that such an effect can be achieved with oral administration.

Administration, Oral↗