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Biomedical subjects

B Charpentier

Publications and source records attributed to B Charpentier.

At least 163 records · Page 9Linked to original sources
PubMed1990

Induction of cytolytic function in resting peripheral blood CD8+/Leu-7+ T cells through IL2/p 75 IL2-receptor interaction: a study in the allogeneic human bone marrow transplantation model.

CD8+/Leu-7+ T cells which circulate in increased proportions in the blood of long-term surviving BMT patients are for the most part high-density resting lymphocytes lacking IL2R-alpha (p55) expression. We show that they can be induced by IL2 to manifest cytolytic function after 24-48 hr stimulation by using rather high concentrations of IL2 (at least 50 U/ml). This function was much more readily induced in high-density CD8+/Leu-7+ T cells than in high-density CD8+/Leu-7+ T cells and occurred in the presence of minimal cell proliferation. Other cytokines involved in primary CTL differentiation (IFN-gamma, IL4 and IL6) were without effect suggesting that CD8+/Leu-7+ T cells are, in the BMT model, in vivo preactivated CTL ready to differentiate into cytolytic effectors under the sole IL2 stimulus. TU27 Mab directed at IL2R-beta (p75) subunit almost completely prevented IL2-induced cytolytic function of CD8+ T cells while 33B3.1 Mab directed at IL2R-alpha (p55) subunit was ineffective, suggesting that the signal for this function has its origin in IL2R-beta chains constitutively expressed by these cells.

Antibodies, Monoclonal↗
PubMed1990

Persistence of donor-specific IL-2-secreting cells and cytotoxic T lymphocyte precursors in human kidney transplant recipients evidenced by limiting dilution analysis.

The low reactivity to donor alloantigens reported in PBL from kidney transplant recipients might be related to clonal deletion and/or suppression of donor-specific alloreactive cells. To discriminate between these two hypotheses, we quantified the number of IL-2 secreting cells (IL-2-SC) and of cytotoxic precursors (CTLp) in the T cells from tolerant recipients when stimulated with either donor specific or nonrelated third-party LCL. To eliminate the irrelevant reactivity, we used as responding cells high-density T cells that had been depleted of such reactivity by 4 days preculture with autologous lymphoblastoid cell line in the presence of bromodeoxyuridine. Thus, frequencies of IL-2-SC and CTLp specifically directed at alloantigens could be measured. In 11 recipients, there was no strong decrease in the frequency of donor-reactive T cells when compared to the frequency of those directed at a third-party lymphoblastoid cell line, either for IL-2-SC (tested in 11 patients) or for CTLp (tested in 6 patients). In three cases of seven, a suppression was observed only when T cells were stimulated by donor cells. These data suggest that donor-reactive cells are still present in PBL of kidney-transplant recipients tested from 6 mo to 4 y posttransplantation. Moreover, suppression of donor-specific cells can be demonstrated in peripheral T cells of some recipients, which may account in part for the absence of rejection.

Histocompatibility↗
PubMed1990

Transplant renal artery stenosis: experience and comparative results between surgery and angioplasty.

One hundred thirty-eight patients with transplant renal artery stenosis (TRAS) were identified among 1200 patients undergoing renal transplantation in our university hospital. Severe systemic hypertension was the main symptom leading to a diagnosis of TRAS. Only 88 TRAS patients were given interventional treatment consisting of percutaneous angioplasty (PTA; n = 49) or surgical repair (SR; n = 39). The immediate success rate was 92.1% for SR and 69% for PTA. The long-term success rate was 81.5% for SR and 40.8% for PTA, with a follow-up period of 56.7 +/- 22.4 months (SR group) and 32 +/- 28.1 months (PTA group). PTA morbidity reached 28%, compared to 7.6% in the SR group. In spite of these results, we still favor PTA as a first line interventional treatment when TRAS is recent, linear, and distal and primary SR in cases of kinking and proximal TRAS.

Adolescent↗
PubMed1990

Decreased lymphokine-activated killer cells in kidney transplant recipients. Correlation with a diminished number of CD3-/NKH1+ cells.

The activity of lymphokine-activated killer cells, measured either by a clonal or polyclonal technique, was assessed in 30 kidney transplant recipients (TX), in 13 hemodialyzed patients (HD-CRI), and in 18 normal (N) controls. A highly significant decrease of the LAK activity in TX in comparison with HD-CRI or N (P = 0.0001) was observed. Moreover, the percentage of CD3-/NKH1+ cells was decreased in TX in comparison with N (P = 0.01). LAK activity was strongly correlated (r = 0.72; P = 0.0001) with the percentage of CD3-/NKH1+ cells and not with that of double-positive CD3+/NKH1+ cells. Multivariate analysis showed that the sole independent variable that determined the LAK activity was the percentage of CD3-/NKH1+ cells: the pathological status (TX, HD-CRI, and N) variable was statistically not significant. On the other hand, two T cell-specific functions (IL-2 secretion and specific cytotoxic activity) were, on the whole, preserved in TX. Altogether, these results suggest that TX are LAK deficient predominantly because they have a decreased number of CD3-/NKH1+ cells. The normality of T cell functions suggests that the high rate of malignancies seen in TX is related to this LAK deficiency. Moreover, our study indicates that, in vivo, CD3+ cells do not significantly contribute to the LAK precursors.

Antigens, CD↗
PubMed1990

Differentiation of F9 embryonal carcinoma cells by synthetic retinoids: amplitude of plasminogen activator production does not depend on retinoid potency or affinity for F9 nuclear retinoic acid receptors.

Retinoic acid and analogues (retinoids) are able to induce the differentiation of F9 murine embryonal carcinoma stem cells into endoderm-like cells. The secretion of plasminogen activator (PA) which accompanies this differentiation is a good index of the biological response of F9 cells to retinoids. We have previously reported that the potency of a series of natural and synthetic retinoids, evaluated by the concentration which provokes half-maximal induction of PA, correlates well with the affinity of these compounds for the endogenous F9 nuclear retinoic acid receptors, but not for the cytosolic retinoic acid binding protein, CRABP. In this paper we show that various retinoids differ, not only in terms of potency, i.e. the dilution at which they are active, but also in terms of the amount of PA that they induce. This parameter, called amplitude, is used to quantify the extent of PA induction by a given retinoid relative to retinoic acid. The amplitude parameters of synthetic retinoids are found to vary over a wide range and are independent of both potency and binding affinity for F9 retinoic acid receptors. It is proposed that the amplitude of the biological response to a given retinoid is the resultant of three factors: (i) the total or partial agonist character of the retinoid; (ii) the binding spectrum of the retinoid for the various types of retinoic acid receptors; (iii) the chemical and metabolic stability of the retinoid in the test system.

Animals↗
PubMed1989

IL-2 receptors on circulating natural killer cells and T lymphocytes. Similarity in number and affinity but difference in transmission of the proliferation signal.

IL-2-binding sites expressed on purified circulating NK cells and high density T lymphocytes were enumerated in 125I-IL-2 binding assays and analyzed by autoradiography after chemical cross-linking of IL-2 to the cells. Quite similar profiles of IL-2R were exhibited by both types of cells consisting of the simultaneous expression of approximately 150 high affinity Tac+ receptors/cell (Kd congruent to 19 pM) and of approximately 540 intermediate affinity Tac- receptors/cell (Kd congruent to 800 pM) which appeared, in cross-linking experiments, to be the isolated 70-kDA protein (p70) subunit of the 55-kDa protein (p55)/p70 heterodimer. The high affinity receptors were distributed on less than 3% of the cells and could be eliminated by complement lysis with anti-p55 mAb. In these conditions, Scatchard analysis no longer revealed two classes of binding sites but only one class of binding sites with intermediate affinity. Although expressed in equal numbers on the surface of NK cells and resting T lymphocytes, the constitutive p70 chains seemed to transmit differently the proliferation signal after effective ligand interaction. Thus, NK cells proliferated strongly in the presence of only 260 pM IL-2, (40 U/ml), whereas resting T cells remained unresponsive to IL-2 concentrations able to saturate the existing p70 receptors (6.5 nM IL-2, 1000 U/ml IL-2) unless monocytes were present. The initiation of cell division seemed to involve the synthesis of p55 chains and the constitution of high affinity receptors as introducing anti-Tac antibody at the start of the cultures inhibited IL-2-induced proliferation. Tac mRNA transcripts accumulated rapidly in NK cells during a 18-h observation period whether anti-Tac antibody was present or not during IL-2 stimulation. In contrast a weak Tac mRNA induction was observed in resting T cells in the same conditions.

Dose-Response Relationship, Immunologic↗
PubMed1989

Conformational behavior of cyclic CCK-related peptides determined by 400-MHz 1H-NMR: relationships with affinity and selectivity for brain receptors.

The conformational study of a homogenous series of cyclic analogues of CCK8, selective for central receptors, such as Boc-X-Tyr(SO3H)-Nle-D-Lys-Trp-Nle-Asp-Phe-NH2, where X = L-Glu, D-Glu, or gamma-D-Glu, was performed by 400-MHz 1H-nmr. The regular increase in affinity for central receptors when going from [L-Glu] to [gamma-D-Glu] is correlated to (a) an enhancement in internal flexibility of the cyclic moiety, (b) an external orientation of the tyrosine side chain, and (c) a restructuring of the C-terminal part of the peptide. All these results could permit a modeling of biologically active conformation of CCK8 for both receptors types to be performed.

Animals↗
PubMed1989

Value of antegrade ureteral dilation for late ureter obstruction in renal transplants.

We report on eight kidney-allografted patients treated for delayed ureteral obstruction between January 1986 and January 1987. In all cases, standard endourological dilation was performed using a balloon catheter, and this was followed by insertion of a pigtail stent. All eight cases showed improvement 1 month after dilation (decrease in creatinine and caliceal dilation). At 6 months, renal function had deteriorated in six patients but remained good in two. One of the six patients was redilated with apparently good results. The remaining five were operated on using their own ureter. We conclude that while internal drainage helps in distinguishing between obstruction and other causes of creatinine increase, antegrade dilation is the treatment of choice for delayed ureteral obstruction.

Catheterization↗
PubMed1989

Synthesis and binding affinities of cyclic and related linear analogues of CCK8 selective for central receptors.

To investigate the role of the sulfate group and the influence of cyclization on the biological properties of conformationally constrained CCK8 analogues, three series of compounds were synthesized: Boc-Glu-Tyr-Nle-D-Lys-Trp-Nle-Asp-Phe-NH2 (1), Boc-Glu-Tyr(SO3H)-Nle-D-Lys-Trp-Nle-Asp-Phe-NH2 (2), and Boc-Glu-Tyr-(SO3H)-Nle-D-Lys-Trp-Nle-Asp-Phe-NH2 (3) (series A); Boc-D-Glu-Tyr-Nle-D-Lys-Trp-Nle-Asp-Phe-NH2 (4), Boc-D-Glu-Tyr(SO3H)-Nle-D-Lys-Trp-Nle-Asp-Phe-NH2 (5), Boc-D-Glu-Tyr(SO3H)-Nle-D-Lys-Trp-Nle-Asp-Phe-NH2 (6), and Boc-D-Glu-Tyr(SO3H)-Nle-D-Nle-Trp-Asp-Phe-NH2 (7) (series B); and Boc-gamma-D-Glu-Tyr-Nle-D-Lys-Trp-Nle-Asp-Phe-NH2 (8), Boc-gamma-D-Glu-Tyr(SO3H)-Nle-D-Lys-Trp-Nle-Asp-Phe-NH2 (9), and Boc-gamma-D-Glu-Tyr-(SO3H)-Nle-D-Lys-Trp-Nle-Asp-Phe-NH2 (10) (series C). The selectivity of these peptides was studied by measuring their ability to displace [3H]propionyl-CCK8 from guinea pig brain and pancreatic membranes. All the peptides displayed low affinities (KI values around 10(-6) M) for the pancreatic receptors (A type). In contrast, both sulfated and nonsulfated cyclic analogues displayed high affinities for central-type binding sites (B type), especially compounds belonging to series C [KI(8) = 4.7 nM and KI(9) = 0.56 nM]. In all series the linear analogues had relatively poor affinities (KI approximately 300 nM) for B-type receptors. Compound 9 was the most potent (KI = 0.56 nM) and selective [KI(pancreas)/KI(brain) = 4464] for central-type CCK receptors of guinea pig. The cyclization of the N-terminal region of CCK8 permits one therefore to obtain probes for central receptors, and small changes directed toward the cyclic part modulate the affinity for these receptors.

Amino Acid Sequence↗