Beneficial effects of oral zinc supplementation on the immune response of old people.

Zinc is known to have beneficial effects on the immune response. In an attempt to modify age-associated immune dysfunction, supplemental zinc was administered to 15 subjects over 70 years of age (220 mg zinc sulfate twice daily for a month). As compared to 15 controls, matched for age and sex, there was a significant improvement in the following immune parameters in the treated group: (1) number of circulating T lymphocytes; (2) delayed cutaneous hypersensitivity reactions to purified protein derivative, Candidin and streptokinase-streptodornase; (3) immunoglobulin G (IgG) antibody response to tetanus vaccine. Zinc treatment had no influence on the number of total circulating leukocytes or lymphocytes, or on the in vitro lymphocyte response to three mitogens: phytohemagglutinin (PHA), concanavalin A (Con A) and pokeweed mitogen (PWM). The data suggest that the addition of zinc to the diet of old persons could be an effective and simple way to improve their immune function.

Modulation of class II histocompatibility antigen expression by maternal serum.

Human maternal serum has been shown to down-regulate the expression of MHC class II antigen in three distinct circumstances. Cord blood mononuclear cells, incubated in the mother's own serum, showed significant modulation of class II antigen expression. This was also the case for unrelated donor lymphocytes, incubated in pooled maternal serum. One neoplastic line (Daudi) was further shown to down-regulate class II antigen expression. In this last case, the down-regulating effect persisted over a 10-day period during which maternal serum was renewed regularly. Retroplacental serum was more MHC class II-inhibiting than peripheral serum. This down-regulating effect does not apply to maternal lymphocytes. The inhibitory effect is thought to be due to a factor, yet to be defined, included in the maternal IgG fraction. Regular assays made throughout pregnancy showed that the class II inhibiting component appears early (5th week), reaches its peak value at the 12th week, and disappears 2 or 3 weeks after delivery.

Single photon emission computerized tomography (SPECT) for monitoring regeneration of the human liver after partial hepatectomy for secondary tumours.

In 18 patients, the liver volume during regeneration after partial hepatectomy for secondary tumours was estimated by single photon emission computerized tomography (SPECT). Hepatic weight index (HWI) was subsequently calculated to follow evolution of the regeneration as a function of postoperative complications over a 30-day period. In patients with postoperative complications the HWI curves initially rose progressively and either reached a plateau or declined thereafter. The same pattern of HWI evolution was observed in patients with tumour recurrence, which was diagnosed later. On the other hand, in patients without postoperative complications the HWI curves rose continuously. These findings showed that a regenerative response was not the same in patients with or without postoperative complications; whereas in patients with tumour recurrence it could additionally provide prognostic information.

[Esophageal scintigraphy and pH measurement in asthmatic adults suspected of having gastroesophageal reflux]. / Scintigraphie et pHmétrie oesophagienne chez des adultes asthmatiques suspects de reflux gastro-oesophagien.

Fifty-five adults with asthma were explored by gastroesophageal scintigraphy (GES) and pH monitoring (3 postprandial hours, 12 nocturnal hours). For their asthma, all patients received theophylline twice a day. Associated digestive symptomatology led to investigations for gastroesophageal reflux (GER). Twelve hours pH monitoring, the reference method, was validated in 13 normal volunteers. During 12 hr pH monitoring, 4 criteria were studied: number of GER, percentage of time at pH 4, number of GER longer than 5 min and longest GER. Acid reflux occurred in 69 p. 100 of cases. Three hours postprandial pH monitoring and GES showed a GER in 40 and 47.5 p. 100 of cases (p greater than 0.05). GES revealed pulmonary aspiration in almost a quarter of asthmatic adults. Detection of a 30 p. cent increment of nocturnal GER by long pH monitoring could explain that results may differ with various techniques. Pulmonary aspiration was more frequent after longer and deeper GER. The mean duration of GER was more than 9 min but it was not significantly different from GER without pulmonary aspiration. GES may be helpful after 12 h pH monitoring because it can prove pulmonary aspiration. Its association with long and intense GER at 12 h pH monitoring suggests definitive surgical treatment of GER in asthmatic patients.

[Computed gamma-tomographic estimation of a hepatic weight index during liver regeneration]. / Mise au point par gammatomographie computérisée d'un index pondéral hépatique au cours de la régénération du foie.

Single photon emission computed tomography was used to evaluate the total functioning liver mass and the regeneration process after partial hepatectomy. Serial tomographic sections were performed after infusion of 99m Technetium. In studies on dogs and in human beings, computed gammatomography enabled to calculate the liver mass with less than 10 p. 100 error. Hepatic regeneration was studied in 10 patients following resection of 46 to 84 p. 100 of the initial liver mass. The remaining liver mass increased rapidly postoperatively and doubled within 13 to 18 days. The regeneration process followed an exponential curve. Assessment of liver regeneration by this non-invasive technique should be of great help following partial hepatectomy.

[Bone scintigraphy in evaluation of bone vascularisation at wrist and hand]. / La scintigraphie osseuse dans l'évaluation de la vascularisation osseuse au niveau de la main et du poignet.

Diphosphonate bone scintigraphy is used since the 1970s for studying bone pathology; it is increasingly common because of increased physical activity of the population. The disphosphonate uptake in bone requires the preservation of bone vascularity and reflects osteoblastic activity; it allows studying the viability of bone. Using data from the literature and our experience, we tried to take stock of its main uses in routine emphasizing the study of vascular and describe its use in fractures of the scaphoid and in the study of vascularised bone transfers. If the value of scintigraphy is well known, the use made by means of pinhole collimator and the market entry of new and more sensitive detectors with better resolution could allow the side of the imaging anatomy of improving the study of the vascularisation of small bone transfers which are increasingly used, particularly at wrist and hand.

In vitro response of human peripheral blood lymphocytes of protein A. DNA synthesis and generation of cells synthesizing the three major classes of Ig.

Increased DNA synthesis and immunoglobulin secretion was observed in human peripheral blood lymphocytes (PBL) cultured in vitro with soluble protein A from Staphylococcus aureus (Sp-A). Optimal Ig secretion was obtained in 6 day cultures containing 1 x 10(6) cells/ml and 10 microgram/ml Sp-A. The presence of 5 x 10(-5) M 2-mercaptoethanol in the culture medium as well as careful selection of foetal calf serum were needed for optimal results. In response to Sp-A stimulation, the three main classes of immunoglobulins were secreted by PBL. In some individuals, concentration of Sp-A optimal for IgG and IgM secretion inhibited IgA production. Immunoglobulin-containing cells were less abundant (0.5--5% of total cells) and smaller in Sp-A than in PWM-stimulated cultures (5--15%). The data suggest that Sp-A and PWM stimulated different subsets of circulating lymphocytes.

Distribution of beta-adrenergic receptors on human lymphocyte subpopulations.

A technique is described allowing the quantification and the characterization of specific beta-adrenergic receptors in intact living human lymphocytes. 125I-Iodohydroxybenzylpindolol, a potent beta-adrenergic antagonist was used to label specific binding sites on unfractionated lymphoid cells and on purified subpopulations of T (F1 and F2) and B cells. F1 and F2 were obtained by filtration through nylon wool column as previously described (Delespesse et al., 1976), they differ in their response to mitogens, and in their interactions with adherent cells and B cells. 125I-HYP binding to unfractionated lymphocytes was a saturable, stereospecific and rapid process with a dissociation constant of 2.5 10(-10) M and a binding capacity of 400--600 sites/cell. Bindings on unfractionated lymphocytes, purified B cells and T cells of the F2 fraction were similar. No detectable binding was noted on T cells from the F1 fraction. Enriched T cells obtained by a rosetting technique displayed 200 receptors/cell.

Modulation of B cell stimulation by maternal serum.

Anti-IgM stimulation of B cells is decreased in the presence of maternal serum as compared to control media. This inhibiting influence of maternal serum is observed during the priming of the B cells. The progression of B cells into cellular proliferation was not influenced by maternal serum. At the level of the immunoglobulin secretion, the influence of maternal serum was also shown. A significant down regulation of the IgM, no change of the IgG production, and an enhanced secretion of IgA and IgE was demonstrated in the presence of maternal serum as compared to control media. It has been suggested that the maternal IgG fraction contains a molecule partly responsible for these changes. Furthermore, the CD23 antigen is increased when B cells are stimulated in the presence of a pool of maternal IgG. All the findings concerning maternal IgG were more pronounced when retroplacental IgG was used instead of peripheral maternal IgG. This observation suggests that the factor responsible for the B cell changes is released at the fetomaternal interface.

N-carbamoyl amino acid solid-gas nitrosation by NO/NOx: A new route to oligopeptides via alpha-amino acid N-carboxyanhydride. Prebiotic implications.

Alpha-N-Carbamoyl amino acid (CAA), whose conditions of formation in a prebiotic hydrosphere have been described previously (Taillades et al. 1998), could have been an important intermediate in prebiotic peptide synthesis through reaction with atmospheric NOx. Nitrosation of solid CAA (glycine or valine derivative) by a 4/1 NO/O2 gaseous mixture (1 atm) yields N-carboxyanhydride (NCA) quantitatively in less than 1 h at room temperature. The crude solid NCA undergoes quantitative oligomerization (from trimer to nonamer under the conditions we used) when treated with a (bi)carbonate aqueous buffer at pH 9. We therefore suggest that part of the prebiotic amino acid activation/polymerization process may have taken place in a dry phase ("drying-lagoon" scenario).

Mechanism of action of maternal serum on the interleukin2 receptor expression.

Neoplastic Jurkat cells were submitted to a PHA stimulation test after a preincubation in maternal or nulliparous serum (10% dilution). The Il2R expression was significantly downregulated among maternal serum treated cells. Retroplacental serum was significantly more inhibitive than peripheral maternal serum (P less than 0.01). The maternal IgG fractions and mostly the retroplacental IgG fraction proved to contain a factor mainly responsible for the Il2R expression inhibitive property. The molecular mechanism of this phenomenon was further studied. It was shown that H7 (acting as a protein kinase inhibitor) could not influence the Il2R modulation. E.G.T.A., a calcium chelator, was not able to interfere with the inhibitive influence of maternal serum. It was suggested that the maternal serum mediated inhibition of the IL2R expression is not influenced by the hydrolysis of membrane bound phosphatidyl inositol. In contrast, pertussis toxin markedly enhanced, in a dose dependent way, the suppressive influence of maternal serum as compared to nulliparous serum. At low concentrations, pertussis toxin lost its stimulating property and retained its ability to ADP ribosylate the alpha subunit of G proteins inducing a release of adenylcyclase mediating cAMP synthesis. This mechanism has been further studied by the addition of dbc AMP or dbc GMP to Jurkat cells preparations stimulated by PHA. dbc AMP, in a dose-related way, induced a downregulation of the IL2R expression of stimulated neoplastic cells preincubated in nulliparous or maternal serum. dbc GMP did not influence the IL2R expression in the same experimental conditions. The maternal serum mediated cells showed the most pronounced IL2R inhibition. Finally, it was shown that the cAMP synthesis by PHA stimulated Jurkat cells was upregulated in a dose dependent way, after a previous cellular incubation in progressive concentrations of maternal serum. In contrast, among nulliparous serum pretreated cells, cAMP synthesis remained significantly lower, after a lectin stimulation, as compared to the cAMP production derived from retroplacental serum treated and stimulated cells. Taken together, these experiments suggest that the maternal serum dependent suppression of the IL2R expression is related to a protein G stimulation followed by an enhanced cAMP synthesis.

Synthesis of Nepsilon-protected-L-lysine and gamma-benzyl-L-glutamate N-carboxyanhydrides (NCA) by carbamoylation and nitrosation.

This paper reports on an original process to synthesize N-carboxyanhydrides, which consists of nitrosating N-carbamoylamino acids with a NO/O(2) gas mixture in acetonitrile. The synthesis of several N-carbamoylamino acids of L-lysine was described using potassium cyanate in water. The latter were then nitrosated to yield the corresponding NCA with more or less efficiency. Indeed, the NCA carrying an acid-sensitive protecting group led to a partial deprotection to give the L-lysine NCA salt. The NCA of N(epsilon)-trifluoroacetyl-L-lysine, N(epsilon)-benzyloxycarbonyl-L-lysine and gamma-benzyl-L-glutamate were successfully synthesized with satisfactory yields. Their polymerizability was compared to that of the N(epsilon)-trifluoroacetyl-L-lysine NCA initiated by n-hexylamine in N,N-dimethylformamide. It also showed that this new process of NCA synthesis could be applied to the synthesis of polypeptides and more generally to the protein chemistry.

In vitro influence of thymopentin on proliferative responses and phytohemagglutinin-induced interleukin 2 production in normal human lymphocyte cultures.

Peripheral human blood lymphocytes from healthy blood donors were investigated in vitro to observe the influence of different doses of thymopentin on nonstimulated proliferation, candidin-stimulated proliferation, and phytohemagglutinin (PHA)-induced interleukin 2 (IL2) production. Concentrations of thymopentin ranging from 0.01 to 10,000 ng/ml were used. The proliferation response in non-stimulated cultures was significantly higher in the presence of 0.01, 1, 10, 1,000, and 10,000 ng/ml of thymopentin. There was no significant increase with 0.1 or 100 ng/ml of thymopentin. Thus, three separate peaks were present in these unstimulated cultures: at a concentration of 0.01 ng/ml; between 1 and 10 ng/ml, and between 1,000 and 10,000 ng/ml. These peaks possibly represent three different subpopulations with different sensitivities to different concentrations of thymopentin. Candidin-induced proliferation was significantly higher only at concentrations of 1 and 10 ng/ml of thymopentin, corresponding to the second peak in the unstimulated culture. No other thymopentin concentrations induced significant increase in the candidin-stimulated cultures. No IL2 production was observed in the unstimulated cultures, even in the presence of thymopentin. On the contrary, preincubation with different concentrations of thymopentin influenced PHA-induced IL2 production. A significant increase in the IL2 level was observed in the supernatant of the cultures if 1,000 ng/ml of thymopentin was used in the preculture period. This concentration corresponds to the third peak in the unstimulated cultures. No significant changes were observed with other concentrations of thymopentin. As the measured value of IL2 is a result of a balance between IL2 production and utilization, the above-mentioned findings need further investigation.(ABSTRACT TRUNCATED AT 250 WORDS)

Functional modifications of the CD4+ and the CD8+ subset due to maternal serum.

Numerous experiments have been performed to try to explain the successful gestation of the semiallogeneic mammalian fetus in the immuno-competent mother. A popular hypothesis is that localized intra uterine suppression mediates the immune response and contributes directly to the survival of the fetus. Suppressive factors synthesized at the fetomaternal interface may be transported by the bloodstream and be found in the retroplacental and peripheral blood circulation. In this report we aim to study these modulating factors by exposing a proteinaceous antigen (Candidine or human mono nuclear cells) to unrelated human lymphocytes in the presence of a pool of maternal serum, retroplacental (MAT SR) or peripheral (MAT SP), or to a pool of male or calf serum (MALS or CS). A significant downregulation of the candidine mediated lymphocytic stimulation was observed in the case of the maternal serum. In order to further characterize this inhibition, a quantitative evaluation of the expression of the CD4 and CD8 positive subpopulations was performed. A selective inhibition of the CD4 positive subset was observed. In the PHA stimulation assay in the presence of maternal serum there was an inhibition of the thymidine uptake of unrelated lymphocytes. When studying the different subsets which were stimulated in the presence of maternal serum and control media it was shown that the CD4 positive subpopulation remained unchanged while there was a slight inhibition of the CD8 positive subset in the first case (maternal serum treated). The same CD4 positive inhibitive property of maternal serum was observed when a neoplastic cell line (HUT cells) was used as target for candidine in a stimulation test. This CD4 inhibited expression remained constant as long as the maternal serum was renewed. Maternal lymphocytes however remained resistant to the inhibitive action of maternal serum and did not show any change in their CD4 and CD8 positive subpopulation. By investigating the different blood components, it was shown that the suppressive factor was included in the IgG fraction and synthesized at the placental level. Appearing quite early during the gestation (at the 5-6th week), this factor was vanishing 2 weeks after the delivery.

Semi-automatic segmentation of gated blood pool emission tomographic images by watersheds:application to the determination of right and left ejection fractions.

Tomographic multi-gated blood pool scintigraphy (TMUGA) is a widely available method which permits simultaneous assessment of right and left ventricular ejection fractions. However, the widespread clinical use of this technique is impeded by the lack of segmentation methods dedicated to an automatic analysis of ventricular activities. In this study we evaluated how a watershed algorithm succeeds in providing semi-automatic segmentation of ventricular activities in order to measure right and left ejection fractions by TMUGA. The left ejection fractions of 30 patients were evaluated both with TMUGA and with planar multi-gated blood pool scintigraphy (PMUGA). Likewise, the right ejection fractions of 25 patients were evaluated with first-pass scintigraphy (FP) and with TMUGA. The watershed algorithm was applied to the reconstructed slices in order to group together the voxels whose activity came from one specific cardiac cavity. First, the results of the watershed algorithm were compared with manual drawing around left and right ventricles. Left ejection fractions evaluated by TMUGA with the watershed procedure were not significantly different (p=0. 30) from manual outlines whereas a small but significant difference was found for right ejection fractions (p=0.004). Then right and left ejection fractions evaluated by TMUGA (with the semi-automatic segmentation procedure) were compared with the results obtained by FP or PMUGA. Left ventricular ejection fractions evaluated by TMUGA showed an excellent correlation with those evaluated by PMUGA (r=0. 93; SEE=5.93%; slope=0.99; intercept = 4.17%). The measurements of these ejection fractions were significantly higher with TMUGA than with PMUGA (P<0.01). The interoperator variability for the measurement of left ejection fractions by TMUGA was 4.6%. Right ventricular ejection fractions evaluated by TMUGA showed a good correlation with those evaluated by FP (r = 0.81; SEE = 6.68%; slope = 1.00; intercept = 0.85%) and were not significantly different (P = 0.42). The interoperator variability with TMUGA was 6.7% for the right ventricle. Thus, the watershed algorithm proposed is an efficient segmentation tool for the semi-automatic analysis of right and left ventricular ejection fractions by TMUGA. Further studies are necessary to check whether this procedure can be used to evaluate ventricular volumes and cardiac outflow.

Modulation of the interleukin 2 receptor by maternal and cord blood serum.

In this report, the potential inhibitive action, of maternal serum (retroplacental and peripheral), and cord blood serum on the expression of the Il2r has been studied. Calf and male serum were used as a control. In order to have an optimal Il2r expression, a previous PHA cellular stimulation was performed. The maternal serum's Il2r inhibitive property was measured during and after the pregnant period. The presence of Il2r on maternal lymphocytes, cord blood cells, and unrelated donor mononuclear cells has been investigated (after a PHA stimulation assay). The downregulated Il2r expression of neoplastic cell line (Hut78 cell line) under the influence of maternal serum has been observed. The examination of the inhibitive action due to maternal serum has suggested that a factor included in the IgG fraction is mainly responsible for the downregulating property concerning the Il2r expression. A possible mechanism for the action of this factor has been studied. Further experiments suggest that the addition of recombinant Il2 during the action of low doses of maternal IgG allows a partial reexpression of the Il2 receptor. However, at physiological concentrations of IgG, the Interleukin 2 receptor downregulation becomes irreversible.

The interleukin-2 receptor on cord blood and nulliparous mononuclear cells is downregulated by maternal and cord blood serum.

The concentration of interleukin-2 receptor (IL-2R) on maternal, cord blood and unrelated nulliparous mononuclear cells has been studied after a previous phytohaemagglutinin (PHA) stimulation. Furthermore, the inhibitive action of maternal and cord blood serum on the IL-2R expression of stimulated nulliparous and cord blood lymphocytes has been shown. A downregulation of the [3H]-thymidine uptake by these PHA treated cells previously incubated in maternal and cord blood serum has been observed. Retroplacental serum was the most inhibitive experimental medium. The IL-2R modulation property of maternal serum has been studied during the pregnancy. Appearing quite early (in the sixth week), the maternal serum dependent inhibitive factor vanished, 2 to 3 weeks after delivery. After a study of the different serum components, it is suggested that the IL-2R downregulating molecule is included in the maternal immunoglobulin (IgG) fraction. Further experiments suggest that the addition of recombinant IL-2 during the action of low doses of maternal IgG allows a partial re-expression of the IL-2R. However, at physiological concentrations of IgG, the IL-2R downregulation becomes irreversible.