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Biomedical subjects

J Nunes

Publications and source records attributed to J Nunes.

31 records · Page 2Linked to original sources
PubMed1989

Monoclonal antibodies against LFA-1 or its ligand ICAM-1 accelerate CD2 (T11.1 + T11.2)-mediated T cell proliferation.

Activation of human-purified T cells can be mediated by pairwise combinations of monoclonal antibodies directed against T11.1 and T11.2 epitopes on the CD2 molecule. Monoclonal antibodies (mAbs) reactive with either the alpha and beta chains of the lymphocyte-function-associated antigen-1 (LFA-1) molecule or one of its ligands, intercellular adhesion molecule-1 (ICAM-1), were found to accelerate anti-CD2-induced proliferation. This effect was seen on thymocytes and resting or preactivated T cells (phytohemagglutinin blasts and alloproliferative T cell clones) and could be observed, following the introduction of anti-LFA-1 or -ICAM-1 mAbs, up to 50 hr after the CD2 stimulatory signal. This effect was equally abrogated by 55 kDa anti-interleukin-2 (IL-2) receptor mAb, but neither the expression of IL-2 receptor nor the production of IL-2 was modified. The effects of anti-LFA-1 or anti-ICAM-1 on T cell activation through the CD2 pathway were therefore opposite to those observed in the CD3 pathway, where both mAbs strongly delayed T cell proliferation.

Antibodies, Monoclonal↗
PubMed1989

T cell activation via the CD2 molecule is associated with protein kinase C translocation from the cytosol to the plasma membrane.

T cell activation via the CD2 molecule involves phospholipase C and phosphoinositide hydrolysis. Here we demonstrate that the triggering of subclones of the human T leukemia Jurkat cell line by anti-CD2 as well as anti-CD3 monoclonal antibodies is able to induce activation (i.e. translocation from cytosol to cell membrane) of protein kinase C (PKC), which is dependent on the formation of 1,2-diacylglycerol from inositol 4-5-bisphosphate. The kinetics of PKC translocation parallels the rise in intracellular calcium following both CD2 and CD3 stimulations. These results further demonstrate that CD2 and CD3 activation pathways use similar signal transduction mechanisms.

Antibodies, Monoclonal↗
PubMed1989

Cholera toxin inhibits the increase in cytoplasmic free calcium induced via the CD2 pathway of human T-lymphocyte activation.

We investigated the action of cholera toxin on the intracellular ionized calcium [Ca2+]i increase induced by anti-CD2 and anti-CD3 monoclonal antibodies in the leukemic human T-cell line Jurkat. Cholera toxin inhibits in a dose-dependent manner these two pathways of human T-lymphocyte activation but with different half maximal inhibition doses (75 ng/ml for CD3, 30 ng/ml for CD2). This effect cannot be accounted for only by the increase in cAMP induced by cholera toxin because forskolin, which raises cellular cyclic adenosine monophosphate (cAMP) to the same levels, induced only a small inhibition of the [Ca2+]i increase in similar conditions. Cholera toxin induced a decrease in the surface expression of the CD3 molecule, suggesting a down-regulation of the CD3 molecules. On the other hand, the expression of CD2 remained unchanged. Cell surface disappearance of the CD3 molecule cannot account for all the inhibitory effects of cholera toxin because CD2 molecule expression was not affected (no modifications in the half maximal binding of anti-CD2 monoclonal antibodies). All together, these results suggest that cholera toxin acts on substrates, possibly G proteins, that could regulate the [Ca2+]i increase induced by anti-CD2 and anti-CD3 mAbs in Jurkat cells. In addition, the present study demonstrated that the rise in cellular cAMP partially inhibits the [Ca2+]i increase induced by anti-CD2 and anti-CD3 mAbs.

Antibodies, Monoclonal↗
PubMed1989

Beta dose point kernels for radionuclides of potential use in radioimmunotherapy.

Beta dose point kernels for 32P, 67Cu, 90Y, 131I, 186Re, and 188Re nuclides appropriate for radioimmunotherapy are calculated based upon Monte Carlo results. The calculations are shown to differ significantly from values based upon solutions to the electron transport equation. Agreement with experiment for 32P is found to be improved for the former as compared with the latter. Values of the scaled dose point kernels are tabulated at 4% intervals of the continuous slowing down approximation range for each of the six radionuclides. Beta dose distributions are also tabulated at corresponding distances from the source. This data may be used to calculate the spatial dose distribution expected following administration of radiolabeled monoclonal antibodies, aiding in optimum selection of the appropriate radionuclide. Parameters for functions providing analytic representation of the calculated scaled dose point kernels of individual beta groups are presented.

Beta Particles↗
PubMed1988

Triggering CD 28 molecules synergize with CD 2 (T 11.1 and T 11.2)-mediated T cell activation.

Pairs of monoclonal antibodies (mAb) defining epitopes T 11.1 and T 11.2 on the CD 2 molecule are mitogenic for purified human T cells in the presence of a submitogenic dose of 12-O-tetradecanoylphorbol 13-acetate (TPA). Anti-CD 28 mAb can substitute for the action of TPA in the anti-CD 2-induced proliferative response of resting T cells, whereas each signal alone is unable to mediate this effect. Co-stimulation by anti-CD 2 plus anti-CD 28 mAb is monocyte independent and besides resting T cells also induces strong proliferation of thymocytes and pre-activated T cells. Modulation of the CD 3-T cell receptor complex does not inhibit the co-stimulatory effects of anti-CD 2 plus anti-CD 28 mAb. The effect is largely dependent on endogenously produced interleukin 2, since the response is strongly inhibited in the presence of mAb against the 55-kDa interleukin 2 receptor chain.

Antibodies, Monoclonal↗
PubMedDate not supplied

Transmembrane signaling via both CD3 and CD2 human T cell surface molecules involves protein kinase-C translocation.

The activation of T lymphocytes by appropriate pairs of anti-CD2 monoclonal antibodies has been shown to involve phospholipase-C and phosphoinositide hydrolysis. In this paper we show that the stimulation of the human cloned leukemic T cell line Jurkat by anti-CD2 as well as anti-CD3 monoclonal antibodies induces translocation from cytosol to cell membrane of protein kinase-C (PKC), which is dependent on the formation of 1,2-diacylglycerol from inositol 4,5-diphosphate. PKC translocation is rapid and transient: the kinetics of enzyme redistribution are similar for CD2 and CD3. These results further stress that CD2 and CD3 T cell activation pathways use similar signal transducing mechanisms.

Antibodies, Monoclonal↗
PubMedDate not supplied

Dissociation between early and late events in T cell activation mediated through CD28 surface molecule.

The regulation of early and late events of T cell activation via the CD28 molecule has been investigated, using as an indicator system the differentiated leukemic T cell line Jurkat. Both CD3 and CD28 mAbs induced an increase in (Ca2+)i in Jurkat cells, although with different kinetics, the latter being slower than the former. CD28-mediated (Ca2+)i mobilization was highly sensitive to cholera toxin (ID50 25 ng/ml, vs 300 ng/ml for CD3 stimulation). The inhibitory action of cholera toxin was neither merely due to the increase in intracellular cAMP concentrations, nor to decrease in cell surface expression of the CD28 molecule. To evaluate the effects of cholera toxin on late events of Jurkat cell activation induced by CD28 and CD3 mAbs, the action of cholera toxin and cAMP and CD3- and CD28-mediated IL-2 secretion was analyzed. CD3-induced IL-2 secretion was highly sensitive to cholera toxin (ID less than 5 ng/ml); on the other hand, CD28-induced IL-2 secretion was poorly sensitive to cholera toxin, in sharp contrast to (Ca2+)i mobilization. On the basis of these data, it is hypothesized that the CD28 pathway could be associated with at least two distinct transduction mechanisms, one responsible for the (Ca2+)i rise in Jurkat cells and highly sensitive to cholera toxin, and the other, whose second messenger is unknown, resistant to cholera toxin and responsible for IL-2 secretion.

Antibodies, Monoclonal↗
PubMedDate not supplied

Toxicosis associated with dual oral exposure of rats to lead and trichloroethylene.

To determine if additive or synergistic toxic effects would occur, adult male rats were exposed orally to lead carbonate (2,000 mg/kg) for 9 days before trichloroethylene (TCE), 2,000 mg/kg, was given concurrently for an additional 7 days. Comparisons were made with groups of vehicle-treated rats and rats given only lead or only TCE. Potential neurotoxicity was evaluated by using the Functional Observational Battery (FOB) recommended for neurotoxicity screening. Rats were sacrificed on day 16, and brain, testes, spleen, kidney/adrenals, heart, and liver weighed and observed for pathological changes. Results of the FOB indicated that lead carbonate was more responsible than TCE for changes observed. Additive or synergistic neurotoxicities were not noted. Histological examination of the kidney from lead-treated rats revealed inclusions, an increased incidence of coagulated proteins, and tubular dilation that was generally more severe in the medullary segments. Gastric and testicular necrosis were found in rats given lead carbonate both with and without TCE (15/20 and 6/20 treated, respectively). The results suggest that, even when given concurrently, the toxicities of lead carbonate and TCE are expressed only as though one toxicant was given.

Administration, Oral↗
PubMedDate not supplied

An evaluation of the EGS4 and CYLTRAN Monte Carlo codes with regard to boundary beta-ray dosimetry by comparison with experimental beta-ray dose backscatter factors.

Beta-ray dose backscatter factors or dose ratios at planar soft-tissue boundaries were calculated using the EGS4/RESTA and CYLTRAN (version 2.1) Monte Carlo codes and these data were compared with experimental results. Since the beta-ray source was 32P, this work addressed the transport of, and energy deposition by, electrons less energetic than 2 MeV. In particular, the simulations targeted the codes' performances with regard to the transport of low energy electrons across material boundaries and the backscattering of low energy electrons. In general, backscatter factors calculated at 7.25 mg/cm2 from several soft-tissue interfaces agreed with experimental values to within about five percent. CYLTRAN was also used to calculate the variation of backscatter factor with distance from aluminum/soft-tissue and air/soft-tissue interfaces and was found to reproduce the shapes of experimental backscatter factor depth profiles.

Beta Particles↗
PubMedDate not supplied

Experimental determination of 32P dose backscatter factors at and near soft-tissue boundaries.

Beta-ray dose backscatter factors with respect to soft tissue were measured using an extrapolation chamber. The beta-ray dose backscatter factor is a measure of the change effected in absorbed dose to a soft-tissue medium when part of the medium is replaced by a material other than soft tissue (i.e., a scatterer); the source is located at the boundary between the two media. The dependencies of backscatter factor on scatterer atomic number and on source geometry are investigated, and the variation of backscatter factor with distance from the boundary is determined. For a 32P point source, backscatter factors with respect to Mylar, a soft-tissue substitute, at 0.55 mg/cm2 from the boundary, are, 29.65[0.12]%, 31.07[0.24]%, 19.30[0.48]%, 16.27[0.35]%, 5.46[0.11]% and -26.44[0.02]% for bismuth, tungsten, cadmium, copper, aluminum, and air scatterers, respectively. Backscatter factors measured for a 32P planar source are generally smaller than those for a point source. The variation of backscatter factor with distance from the boundary is well represented analytically by sums of exponentials. Therefore, the rate of decrease of backscatter factor with distance can be specified by a relaxation length, defined as the depth through which the backscatter factor is reduced by 1/e, where e is the base of the natural logarithm. For example, with a 32P planar source, relaxation lengths in Mylar are 588[7] mg/cm2 and 238[2]mg/cm2 for bismuth and aluminum scatterers, respectively. Qualitative interpretation of backscatter factor depth profiles is presented. In addition, the variations of backscatter factor with scatterer atomic number and with source geometry are discussed with reference to existing experimental findings on beta particle reflection.

Beta Particles↗
PubMedDate not supplied

[The clinical implications of the characteristics of uteroplacental flow in pregnancy complicated by hypertension].

The study of the relationship between maternal and perinatal outcome with uterine blood flows using a continuous wave Doppler unit, in hypertensive patients was the aim of our work. One hundred and thirty seven pregnant hypertensive women seen and delivered at the Department of Obstetrics, Santa Maria Hospital, Lisbon, were included in the study. Blood flows were classified as abnormal if and when the systolic/diastolic ratio was > 2.8 and/or a diastolic notch was seen in one or both uterine arteries. The cases were divided in 2 groups (normal/abnormal) according to the uterine blood flow and correlated with maternal and perinatal outcomes. Twenty-three of 26 maternal complications occurred in cases with abnormal uterine artery blood flow; we also found the large majority of perinatal complications within this group (100% perinatal deaths, 88% of the intrauterine growth retardation, 92% preterm deliveries, 93% fetuses with absent or reverted diastolic umbilical flow, 88% cardiotocographic patterns of fetal distress and 84% of the newborns admitted to the neonatal care unit). In conclusion, in pregnancies complicated by hypertension, uterine artery blood flow evaluation by continuous wave Doppler may identify a set of patients needing closer prenatal surveillance.

Female↗