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81.
Elimination of B-lineage leukemia and lymphoma cells from bone marrow grafts using anti-B4-blocked-ricin immunotoxin 总被引:2,自引:0,他引:2
Denis C. Roy Claude Perreault Robert Bélanger Martin Gyger Christiane Le Houillier Walter A. Blättler John M. Lambert Jerome Ritz 《Journal of clinical immunology》1995,15(1):51-57
Bone marrow is the primary site of disease in patients with acute lymphoblastic leukemia (ALL) and is frequently involved in patients with non-Hodgkin's lymphoma (NHL). At the time of autologous bone marrow transplantation, marrow grafts from patients with leukemia and lymphoma are often still contaminated by malignant cells, even when such patients achieve complete clinical remission. In this study, we evaluated the potential of anti-B4-blocked-ricin (anti-B4-bR) immunotoxin to eliminate residual ALL and NHL cells from bone marrow. Anti-B4-bR binds to the CD19 antigen, which is B-lineage specific, and, at concentrations of 5×10–9
M or greater, could eliminate more than 3 logs of CD19+ Nalm-6 or Namalwa cells in a 20-fold excess of normal irradiated bone marrow after only 5 hr of incubation. This activity was abrogated by the addition of anti-B4 but not by the presence of galactose, which is the natural ligand for native ricin. Also, when used at these high concentrations, anti-B4-bR showed little nonspecific toxicity against normal hematopoietic progenitors. In conclusion, a single short exposure to anti-B4-bR is capable of inducing high levels of depletion of CD19+ leukemia and lymphoma cells without significant nonspecific toxicity against normal marrow progenitors. Therefore, anti-B4-bR offers an interesting approach to the elimination of B-lineage malignant cells prior to autologous bone marrow transplantation. 相似文献
82.
Berlier W Bourlet T Lawrence P Hamzeh H Lambert C Genin C Verrier B Dieu-Nosjean MC Pozzetto B Delézay O 《Journal of medical virology》2005,77(4):465-474
X4 and R5 HIV strains are present in the semen of men infected with HIV but R5 isolates are transmitted preferentially. The role of human epithelial cells in this selection is addressed. Three human cervical cell lines-CaSki, SiHa, and HEC1A-and normal human vaginal cells from HIV-negative donors were characterized for HIV receptor expression and incubated with X4 and R5 laboratory-adapted strains or primary isolates. The infection was assessed by detection of intracellular HIV DNA. The three cell lines were shown to express on their surface the CXCR4 and GalCer molecules, but not the CD4 and CCR5 ones. The three cell lines and normal human vaginal cells were found to be selectively permissive to X4 HIV entry; the preincubation of the cell lines with rhSDF-1 inhibited this infection. The detection of the intracellular proviral DNA in the cell lines and in normal human vaginal cells demonstrated a selective integration of X4 strains. Additional experiments showed that no extracellular RNA was detected in the supernatants of HEC1A cells infected by X4 isolates either after 18 days of culture or after incubation with PHA-stimulated PBMCs and that no transmission occurred after co-culture between infected HEC1A cells and PHA-stimulated PBMCs. These results suggest specific sequestration of X4 strains by genital epithelial cells, which could explain, at least in part, the HIV tropism selection process during sexual intercourse. 相似文献
83.
Zahariev A Bergouignan A Caloin M Normand S Gauquelin-Koch G Gharib C Blanc S 《European journal of applied physiology》2005,95(4):344-350
Because body composition is altered during head-down bed rest (HDBR), body mass can not be used as an index of energy balance.
Consequently diet allowances should not be based on body mass evolution but on fat mass changes. Though criticized, skinfold
thickness (ST) is the costless, easiest and fastest method to use for such an objective. The aim of this study was to compare
the percentage of body fat (%BF) estimated by ST with the isotope dilution of H218O. We compiled data from three HDBR campaigns, one on women (n=8) in November 1998 and two on the same men (n=8) in December 1997 (without countermeasure) and January 1998 (with thigh-cuffs countermeasure), according to a crossover
design. Body composition was assessed before and after 6 days of HDBR. %BF was derived from the biceps, triceps, sub-scapular
and sup-iliac ST according to Durnin and Wormersly (1974). Fat-free mass was measured on the same day by H218O dilution and fat mass was calculated by the difference with body mass and expressed as a percentage. Based on precision
tests, the minimum measurable change by ST was 1.1%BF for single measurement point. Both intercepts (F
4,30=0.89, P=0.45) and slopes (F
4,30=0.74; P=0.57) of the ST versus dilution relationships were not affected by the periods (December vs January), experimental conditions
(control vs HDBR vs HDBR + thigh cuffs) or sex allowing the derivation of a common relationship %BFst=0.94 × %BFdil (F
1,47=97.9, P<0.0001; non-significant intercept excluded) with a bias between methods of −1.7±2.0 %BF (95% CI: −5.8, 2.4 %BF). ST can be
used to measure %BF during HDBR provided great care is placed on training and changes are higher than 1.1 %BF. If the method
can be applied for in-flight energy balance monitoring given the high observed energy deficit, a tight monitoring of the individual
nutritional status as needed during simulation appears, however, dubious based on this solely method. 相似文献
84.
Martinez X Regner M Kovarik J Zarei S Hauser C Lambert PH Leclerc C Siegrist CA 《Virology》2003,305(2):428-435
The relative immaturity of the neonatal immune system limits CD4(+) Th1 and cytotoxic T lymphocyte (CTL) responses, and represents a significant challenge for the development of vaccines against intracellular pathogens. In this report, we demonstrate the ability of a non-replicative delivery system based on parvovirus-like particles (VLP) to induce CTL responses in the neonatal period. A single immunization of 1-week-old BALB/c mice with recombinant VLP carrying a CD8(+) T cell determinant from lymphocytic choriomeningitis virus (VLP-LCMV) induced antigen-specific CD8(+) cytotoxic T cells that were similar to those elicited by adult immunization, as assessed by cytotoxic activity, interferon (IFN)-gamma secretion, cytotoxic precursor cell frequencies, in vitro avidity for antigen and protective activity against viral challenge. These CTL responses are elicited within 2 weeks of a single immunization, in the absence of adjuvant and independently of the presence and help of CD4(+) T cells, highlighting the potential of VLP as candidate vaccine vectors in early life. 相似文献
85.
Using two chronobiological variants ofSchistosoma mansoni (a blood fluke infecting man) from Guadeloupe (French West Indies), we carried out experimental crossbreeding between schistosomes with an early and those with a late cercarial shedding pattern. The results obtained on the F1 (intermediate shedding patterns) and F2 generations (early, intermediate, and late patterns) demonstrate that the cercarial emergence rhythms of schistosomes are genetically determined. This genetic variability is interpreted as a consequence of the selective pressure exerted by the two different hosts (man and rat) implicated in the life cycle ofS. mansoni from the Guadeloupean focus of schistosomiasis.This work received financial support from the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases and the CNRS. 相似文献
86.
Paul Fréneaux Claude Nos Anne Vincent-Salomon Pascal Genin Brigitte Sigal-Zafrani Abir Al Ghuzlan Marie-José Birolini Krishna Clough Xavier Sastre-Garau 《Modern pathology》2002,15(6):641-646
There is no consensus method for the histological analysis of axillary sentinel nodes (SN). This study aimed to (1) assess the rate of occult metastases in SN using large serial sectioning and immunohistochemistry (IHC), (2) evaluate whether occult metastases were predictive of metastases in the downstream axillary nodes, and (3) specify a methodology of analysis of SN that could be both sensitive and applicable in daily practice. One hundred three patients with breast carcinoma underwent SN biopsy and then axillary dissection. SN free of tumor at standard examination of one section were sectioned at six levels (150-microm intervals) and immunostained for cytokeratin. The number and localization of labeled metastatic cells (occult metastases) were recorded. In 29 of the 103 patients (28%), SN were found to be metastatic after standard examination. The SN of the remaining 74 patients were further analyzed using IHC. Occult metastases were detected in 35 of these patients (47.3%), leading to an overall SN involvement rate of 62% (29+35/103). In 33 of these 35 cases, the plurality and the dispersion of the immunostained cells implied that the screening of only 3 of the 6 levels would have led to the detection of diagnostic positive events. Only one of the 35 patients (2.8%) with occult metastases showed metastatic lymph node in the downstream axilla. In our series of axillary SN, the analysis of one standard histologic section and, when negative, of only three additional sections after IHC revealed >60% of metastasis or occult metastasis. Metastasis detected by standard analysis had a high predictive value of downstream node metastasis, whereas the predictive value of occult metastasis revealed by IHC was poor. The clinical significance of occult metastases in SN needs to be specified by long-term follow-up analysis. 相似文献
87.
88.
Claire Bihoreau Agns Heurtier Alain Enjalbert Nicole Corvaïa Armand Bensussan Laurent Degos Claude Kordon 《European journal of immunology》1991,21(11):2877-2882
A monoclonal antibody (OKT3) directed against the T cell receptor (TcR)/CD3 molecular complex, as well as a protein kinase C (PKC) activator (phorbol 12-myristate 13-acetate, PMA) were added to a culture of tumoral Jurkat T cells, in order to precise the sequence of intracellular signals leading to T cell activation. The experiments were performed in the presence or in absence of various stimulators of adenylate cyclase (AC) such as forskolin (FK), cholera toxin (CT) or prostaglandin E2 (PGE2). OKT3 increased inositol phosphate (IP) production; in parallel, it induced a slight accumulation of cAMP. The effect was markedly potentiated in presence of FK or CT, and to a lesser extent in the presence of PGE2. FK stimulated adenylate cyclase of Jurkat cell membranes, but the effect was not potentiated by OKT3, suggesting that potentiation of cAMP accumulation requires intact cells and is not mediated by direct receptor coupling. On the other hand, elevated cAMP accumulation induced a negative feedback on IP production. The effect of OKT3 on cAMP was mimicked by A23187, a Ca2+ ionophore, and abolished in the absence of extracellular Ca2+. PMA had the same effect as OKT3 on basal or FK- and CT-induced accumulation of cAMP. In contrast, it inhibited the PGE2 effect on the cyclic nucleotide. After desensitization of PKC by pretreatment with a high concentration of PMA, the phorbol ester was no longer effective. Under those conditions, facilitation by OKT3 of FK-induced accumulation of cAMP was preserved, whereas potentiation by the monoclonal antibody of the PGE2 stimulation of AC was even enhanced. The data indicate that cAMP accumulation indirectly elicited by phospholipase C activation is, at least partly, mediated by IP-dependent Ca2+ mobilization, while PKC is preferentially effective as an inhibitor of PGE2 stimulation. 相似文献
89.
Claude Penit Bruno Lucas Florence Vasseur Theresa Rieker Richard L. Boyd 《Clinical & developmental immunology》1996,5(1):25-36
The development of thymocyte subsets and of the thymic epithelium in SCID and RAG-2-/– mice was monitored after normal bone-marrow-cell transfer. The kinetics of thymic
reconstitution and their relationships with cell proliferation were investigated by using
bromodeoxyuridine to detect DNA-synthesizing cells among lymphoid cells by 3-color
flow cytometry, and in epithelial compartments by staining frozen sections. Thymocytes
started to express CD8 and CD4 10 days after transfer, simultaneously with extensive proliferation.
The first mature CD4+ single-positive cells were generated, from resting CD4+CD8+
cells after day 15. During this day 10–15 period, many epithelial cells positive for cortexspecific
or panepithelial markers were labeled with BrdUrd after pulse-injection. Organized
medullary epithelium also developed after day,15, that is, synchronously with the
appearance of mature thymocytes, but medullary cells were never found BrdUrd+. These
results suggest that, in these models, the reconstitution of the thymic epithelial network
proceeds through expansion of preexisting cortical or undifferentiated cells and by later
maturation (acquisition of specific markers) of medullary cells. This last process is dependent
of the presence of mature thymocytes. 相似文献
90.
The distribution and metabolism of ACTH and the dynamics of the adrenal cortical response to this tropic hormone were characterized
in the rat, through mathematical models involving data derived from experiments, where plasma corticosterone concentrations
were measured following both single injections and infusions of ACTH. The models, which incorporate a previously established
model of the dynamics of plasma corticosterone, were statistically validated. The simulated dynamics of the different processes
linking ACTH secretion by the adenohypophysis to corticosterone secretion by the adrenal cortex include: (1) a variable MCR
for plasma ACTH, modeled as the sum of a constant and a saturable degradation process; (2) the ability of the adrenal gland
to secrete at a maximal rate aven after the plasma ACTH concentration has become negligible, modeled as the accumulation of
an intermediary productZ directly controlled by the plasma ACTH concentration; (3) a saturable secretion with a small time constant and which, for
single injections, always starts in the same fashion, modeled as a “synthesis process” whose input is a saturable function
ofZ; (4) an immediate fall of the plasma corticosterone concentration at the end of the ACTH infusions, modeled as a “release
process” also controlled byZ.
Supported by grants from the Medical Research Council of Canada (MT-1205, MT-1555, and MA-4970), and from INSERM, France (CRL-76-5-020-4). 相似文献