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Biomedical subjects

A Bernard

Publications and source records attributed to A Bernard.

At least 451 records · Page 25Linked to original sources
PubMed1988

[Host-graft interactions after allogenic bone marrow transplantation; choice of donor].

The complexity of host-graft interactions after bone marrow transplantation explains the criteria of choice of the donor. Graft rejection, graft-versus-host disease, graft-versus-leukemia, delayed immune reconstitution, often associated or mutually exclusive are observed even with an HLA identical sibling donor. Syngeneic transplants may be complicated by leukemic relapse related to the loss of the graft-versus-leukemia effect. The compilation of files of unrelated donors increases the possibility of finding a matched unrelated donor. Preliminary results suggest that clinical results may be equivalent to those achieved with HLA identical sibling donors. Overall results of HLA mismatched transplants are disappointing because of the increase of immunological complications. Attempts at preventing graft-versus-host disease with T cell depletion led to an increase of immunological complications: rejection and leukemic relapse. Modifications of the conditioning regimen and use of in vivo monoclonal antibodies are currently being investigated. Ethical, legal, and psychological considerations have also to be taken into account in the donor choice especially with the increase of the donor pool.

Bone Marrow Transplantation↗
PubMed1987

Interleukin 2 up-regulates its own production.

It has been previously reported that a combination pair of anti-CD2 monoclonal antibodies (mAb) T11(2)+T11(3) induces a strong proliferation of T cells, which does not require the involvement of accessory cells and exogenous interleukin 2 (IL-2). More recently, we have shown that the requirement for optimal T cell proliferation depends on the combination pairs of anti-CD2 mAb used. Among them, anti-GT2+T11(1) mAb do not allow optimal proliferation of TA4 helper cloned T cells due, at least in part, to a low level of IL-2 production. This observation offered us the opportunity to study the effect of IL-2 on its own production. We show here that stimulation of cloned TA4 cells with anti-GT2+T11(1) mAb induces only a marginal level of IL-2 production. By contrast, significantly higher levels of IL-2 activity are detected in the culture supernatant of TA4 cells preincubated with recombinant IL-2 (rIL-2) before stimulation with anti-GT2+T11(1) mAb. This effect is dose-dependent over a wide range (5 to 50 IU/ml) of rIL-2 concentrations added during preincubation time. In addition, it is not due to carryover of rIL-2 bound during the preincubation time, or to lesser IL-2 consumption by these cells, or to increasing numbers of IL-2-producing cells induced by exogenous IL-2. Moreover, the observation was confirmed with IL-2 mRNA. Although neither rIL-2 nor anti-GT2+T11(1) mAb alone could induce a significant production of IL-2, rIL-2 appears to up-regulate its own production when the TA4 cells are activated by the anti-CD2 mAb-mediated second signal.

Antibodies, Monoclonal↗
PubMed1987

Regulation of helper T cell clone proliferation via the CD2 molecule.

We have investigated the requirements for CD2-induced proliferation of a CD4+, CD8-, CD3+, CD2+ antigen-specific, class II-restricted proliferating cloned cell line. A combination pair of two monoclonal antibodies (MoAb) recognizing, respectively, TII1 and D66 epitopes on the CD2 molecule was used as a stimulus. The regulatory function of accessory cells and various interleukins in this proliferation was determined. The results show that although this clone was able to proliferate in the absence of accessory cells (AC) or interleukin 1 (IL-1) when stimulated by these MoAb, AC constantly enhanced the response to these MoAb. AC acted by increasing high-affinity IL-2 receptor expression. On the contrary they did not play any role in IL-2 production. This regulation of IL-2 receptor expression by AC was specific of adherent cells, did not involve Fc receptors, was impaired when AC were metabolically inactivated and did not require T cell-AC interaction via LFA1, CD4, or HLA molecules. The AC function was not abrogated by anti-IL-1 antibodies and could not be replaced by exogenous IL-1. These results were compared to previously described AC effects on resting T-cell proliferation when stimulated with the same pair of anti-CD2 MoAb. Clear differences in activation requirements in resting and activated T cells via CD2 molecules were found.

Antibodies, Monoclonal↗
PubMed1987

Three different erythrocyte surface molecules are required for spontaneous T cell rosette formation.

We have obtained three anti-sheep erythrocyte (E) monoclonal antibodies (MAb) which block rosettes with human T cells. They also block rosettes with E from all the species we have tested, including rosettes with autologous E. They define three different minor components on the E surface: MAb N217 precipitates a single 42-kilodalton (kDa) chain and MAb N4 a single 14-kDa chain, and MAb N23 immunoprecipitates under nonreducing conditions a single band at approximately 220 kDa, which is resolved under reducing and alkylating conditions, in two bands migrating at approximately 110 kDa and approximately 220 kDa. Thus MAb N23 is likely to react with a complex made of covalently linked 100-kDa chains associated in a noncovalent fashion with approximately 220 kDa chains. In addition, we have observed a puzzling phenomenon, i.e., that binding the MAb N23 first increases, to a large extent, the amount of N4 epitopes which can be subsequently detected on E. This effect was not observed when N217 MAb or antiglycophorin (either monoclonal or polyclonal) antisera were first bound on E. Therefore the N23 and N4 molecules must interact on the E surface. This finding discloses the complex interactions between the T cell and E surface component that must occur in the process of rosette formation, including that with autologous E. These observations are of interest in view of the recent evidence that the CD2 molecule is involved both in adhesion and activation aspects of T cell functioning.

Antibodies, Monoclonal↗
PubMed1987

A cross-sectional survey of kidney function in refinery employees.

We examined sensitive biochemical and immunological markers of kidney function and damage in 53 male oil refinery workers exposed to hydrocarbons and compared their results with those of a control group of 61 age-matched nonexposed males. The mean duration of employment of exposed males was 11 years. The current levels of exposure to a variety of aliphatic and aromatic hydrocarbons, as determined by personal monitoring, were well below the current threshold limit values. No difference was found in the urinary tubular parameters beta-N-acetyl-D-glucosaminidase, beta 2-microglobulin (beta 2-m) and retinol-binding protein. Similar serum beta 2-m levels indicated no impairment of the glomerular filtration rate in the exposed workers. The levels of circulating immune complexes were also identical in both groups. The mean albuminuria was slightly higher (p less than .005) in the exposed group in a quantitative assay but was not dipstick-detectable. The mean urinary excretion of a renal antigen was also higher (p less than .05) in the exposed group and correlated with the excretion of albumin. Finally, slightly higher titers of anti-laminin antibodies were found in five exposed employees, but this was not accompanied by an increased albuminuria. We conclude that chronic low-level hydrocarbon exposure in these refinery workers does not lead to clinically significant renal abnormalities. Nevertheless, some findings are consistent with the possible role of hydrocarbon exposure in the induction of renal disturbances.

Adult↗
PubMed1987

Early detection of the nephrotoxic effects of industrial chemicals: state of the art and future prospects.

This paper discusses several tests that may permit the early detection of renal changes induced by long-term exposure to nephrotoxic industrial chemicals and may possibly serve as advance warning of pending renal damage. Some tests mainly attempt to assess the integrity of the glomerulus: high molecular weight proteinuria, glomerular basement membrane (GBM) antigens in blood and in urine, circulating anti-GBM antibodies, glomerular filtration rate after an acute oral load of proteins, and estimation of membrane negative charges (ie, glomerular polyanion). Others mainly attempt to identify functional and/or morphological changes at the tubular level: low molecular weight proteinuria, aminoaciduria, glucosuria, hyperphosphaturia, hypercalciuria, enzymuria, tubular antigen excretion, kallikrein, and prostaglandin excretion. Some of these tests are already routinely used, although controversy may still persist with regard to their clinical significance. Recently, new tests have been developed that may open new perspectives for assessing the significance of the early renal changes induced by chemicals.

Autoantibodies↗
PubMed1987

Epidemiological survey among workers exposed to manganese: effects on lung, central nervous system, and some biological indices.

A cross-sectional epidemiological study was carried out among 141 male subjects exposed to inorganic manganese (Mn) in a Mn oxide and salt producing plant (mean age 34.3 years; duration of exposure, mean 7.1 years, range 1-19 years). The results were compared with those of a matched control group of 104 subjects. The intensity of Mn exposure was moderate as reflected by the airborne Mn levels and the concentrations of Mn in blood (Mn-B) and in urine (Mn-U). A significantly higher prevalence of cough in cold season, dyspnea during exercise, and recent episodes of acute bronchitis was found in the Mn group. Lung ventilatory parameters (forced vital capacity, FVC; forced expiratory volume in one second, FEV1; peak expiratory flow rate, PEFR) were only mildly altered in the Mn group (smokers) and the intensity and the prevalence of these changes were not related to Mn-B, Mn-U, or duration of exposure. There was no synergistic effect between Mn exposure and smoking on the spirometric parameters. Except for a few nonspecific symptoms (fatigue, tinnitus, trembling of fingers, increased irritability), the prevalence of the other subjective complaints did not differ significantly between the control and Mn groups. Psychomotor tests were more sensitive than the standardized neurological examination for the early detection of adverse effects of Mn on the central nervous system (CNS). Significant alterations were found in simple reaction time (visual), audioverbal short-term memory capacity, and hand tremor (eye-hand coordination, hand steadiness). A slight increase in the number of circulating neutrophils and in the values of several serum parameters (ie, calcium, ceruloplasmin, copper, and ferritin) was also found in the Mn group. There were no clear-cut dose-response relationships between Mn-U or duration of Mn exposure and the prevalence of abnormal CNS or biological findings. The prevalences of disturbances in hand tremor and that of increased levels of serum calcium were related to Mn-B. The response to the eye-hand coordination test suggests the existence of a Mn-B threshold at about 1 microgram Mn/100 ml of whole blood. This study demonstrates that a time-weighted average exposure to airborne Mn dust (total dust) of about 1 mg/m3 for less than 20 years may present preclinical signs of intoxication.

Adult↗
PubMed1987

Evaluation of the nephrotoxic potential of styrene in man and in rat.

The urinary excretion of beta 2-microglobulin, retinol-binding protein and albumin was measured in 65 workers exposed to styrene at levels averaging 50 percent of the current threshold limit value (215 mg/m2) for 1-13 years (mean: 6 years). By comparison with a control group matched for age and socioeconomic status, no significant difference was observed in the urinary excretion of proteins. In rats, styrene was weakly nephrotoxic. No functional or morphological renal change could be disclosed in rats exposed to 565 mg of styrene/m3, 5 days/week for 13 weeks. The repeated i.p. injection of 1 g styrene/kg (1/5 of oral LD50) for 10 days induced only a slight tubular dysfunction as evidenced by a 5-fold increase in beta 2-microglobulinuria. Altogether, these epidemiological and experimental data suggest that the current threshold limit value for styrene (215 mg/m3) proposed by the American Conference of Governmental and Industrial Hygienists does not entail any risk of renal toxicity.

Adult↗
PubMed1987

Frequency analysis of human peripheral blood B cells sensitive to CD2 monoclonal antibody-activated T cells.

Recent studies have demonstrated that appropriate pairs of cluster of differentiation 2 (CD2) monoclonal antibodies (MoAbs) directed against two epitopes on the T11 molecule induced human T-cell activation leading to the production of several lymphokines. Here we report that human peripheral blood B lymphocytes cultured in the presence of the CD2 (D66 + T11) MoAb, together with T lymphocytes and monocytes, secreted larger amount of immunoglobulin (Ig) than when they were incubated in the same culture conditions in the presence of pokeweed mitogen (PWM). We further show that the level of Ig secreted by the progeny of a single responsive B cell is similar in both systems and demonstrate that the increase in the Ig concentration is directly related to the high frequency of B-cell precursors sensitive to CD2 MoAb-activated T cells.

Antibodies, Monoclonal↗
PubMed1987

Blood cell kinetics and total body irradiation.

The early response of blood cells to irradiation has been studied in leukemia patients who received total body irradiation (TBI) prior to cyclophosphamide and bone marrow transplantation. After a single session treatment (10 Gy in 4 h) the most dramatic variation was observed in the granulocytes. At the end of the irradiation their concentration was 2 to 6 times higher. Because of a subsequent rapid decline, the peak may be overlooked if the blood counts are delayed. Lymphocytes decreased to 50% at the end of the single session TBI and continue to decrease exponentially, with a half time of 30 h. During a fractionated irradiation (11 X 1.2 Gy in 4 days) the lymphocyte number dropped to 60%, 13 h after the first fraction and this decline continued with a half time of 30 h during the treatment. From the data obtained in vivo, a lymphocyte D0 value of 1.2 Gy was computed. The lymphocyte subsets (B.T. OKT4 OKT8) did not exhibit different radiosensitivities either in vivo or in vitro. The disappearance of lethally hit lymphocytes from the blood exhibits a biphasic kinetic: 50% of the cells disappear in a few hours and 50% with a half time at 30 h. Lymphocytes irradiated either in vitro or in vivo when in culture disappear slowly, contrasting with the in vivo findings. It may suggest that lethally hit lymphocytes are quickly removed from the circulating pool in vivo.

Blood Cell Count↗
PubMed1987

Role in T-cell activation for HLA class I molecules from accessory cells: further distinction between activation signals delivered to T cells via CD2 and CD3 molecules.

The immunological function of major histocompatibility complex molecules, including HLA class I molecules, is to present antigens and/or their processed peptides to various lymphocyte subpopulations. Thus, they play a pivotal role in regulatory interactions between cells of the immune system, which can result in the activation and function of T cells. We looked for a role of major histocompatibility complex molecules during T-cell activation induced by monoclonal antibody (mAb) or combinations of mAb recognizing the two well-characterized T-cell surface molecules CD3 and CD2. To activate T-cell peripheral blood lymphocytes, we used a CD3 mAb or two different pairs of CD2 mAb, CD2 "GT2 + T11(1)" and CD2 "D66 + T11(1)," which, as we have previously shown, deliver different signals of activation to T cells. Anti-HLA class I mAb blocked the activation induced by CD3 mAb or by CD2 GT2 + T11(1), but it did not block activation induced by CD2 D66 + T11(1). We observed this pattern of inhibition according to the stimulus used to activate T cells both when the anti-HLA class I mAbs were added to cultures of whole peripheral blood mononuclear cells and when they were fixed to monocytes only. In the latter case, purified monocytes were first incubated with the anti-HLA mAb (whether whole immunoglobulin or Fab fragment) and then fixed with paraformaldehyde before culture with autologous purified T cells. Anti-HLA class I fixed on monocytes prevented both interleukin 2 (IL-2) receptor expression and IL-2 synthesis on T cells. The inhibitory effects of anti-class I mAb bound to monocytes were not reversed by adding large amounts of recombinant IL-2 or recombinant IL-1, a finding consistent with the observations that accessory cells surface components can fully complement the signals directly delivered to T cells by CD2 or CD3 mAb. We conclude that HLA class I from accessory cells plays an important role in the early phase of T-cell activation when direct contacts between accessory cells and T cells are required.

Antibodies, Monoclonal↗