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Anne Moreau

Publications and source records attributed to Anne Moreau.

At least 19 recordsLinked to original sources
PubMed2005

A uniform activated B-cell-like immunophenotype might explain the poor prognosis of primary central nervous system lymphomas: analysis of 83 cases.

Most primary central nervous system lymphomas (PCNSLs) in immunocompetent patients are diffuse large B-cell lymphomas (DLBCLs), characterized by poor prognosis, compared with systemic forms. A germinal center B-cell-like (GCB) origin of PCNSL was hypothesized on the basis of BCL-6 expression and ongoing mutational activity. Our goal herein was to determine, for 83 PCNSLs, the percentages of GCB and activated B-cell-like (ABC) phenotypes and their prognostic significance. CD10, BCL-6, MUM1, BCL-2, and CD138 antigens were immunohistochemically labeled on paraffin-embedded sections; the first 4 were positive in 2.4%, 55.5%, 92.6%, and 55.5% of the tumors, respectively. None of the 56 tested samples expressed CD138. Among the 82 patients with complete information, 79 (96.3%) were classified as ABC; 42 (51.2%) expressed BCL-6+ MUM1+, suggesting an "activated GCB" origin; 33 (40.2%) were exclusively MUM1+, and the remaining 4 (4.9%) were negative for all markers tested. These findings provide new insights into interpreting the poor PCNSL prognostic, which may, in part, be due to biologic aggressiveness associated with its activated B-cell-like pattern. We postulate assigning PCNSL a histogenetic "time-slot," overlapping late GC and early post-GC, that could explain the predominant ABC phenotype observed.

Adult↗
PubMed2005

Exhaustive depletion of graft resident dendritic cells: marginally delayed rejection but strong alteration of graft infiltration.

BACKGROUND: Donor dendritic cells (DDC) are believed to sustain direct recognition leading to acute allograft rejection. However, DDC are also required for tolerance induction in various models. METHODS: We studied the effect of DDC depletion on major histocompatibility complex (MHC) mismatched rat heart allografts in a strain combination characterized by a DDC-dependant tolerance induction. Grafts were depleted of DDC either by pretreating donors with cyclophosphamide (CyP) or by being parked in an intermediate recipient treated with cyclosporine A (CsA). RESULTS: CyP depleted 95% of resident DC and no specific donor MHC class II staining was observed in parked grafts. Parked grafts survived significantly but only moderately longer than untreated grafts (10.8+/-1.9 days vs. 6.5+/-0.5 days; P<0.05). Compared to unmodified grafts, on day 5 after transplantation, the magnitude of the graft infiltrate was dramatically decreased in DDC-depleted grafts, with IgG deposition within the grafts at the time of rejection. In parallel, the cytokine transcript levels were also lower in these grafts on day 5, but reached levels similar to those of unmodified grafts by day 7, indicating a delayed pattern of rejection. CONCLUSIONS: Taken collectively, these data suggest that DDC depletion has a greater effect on the capacity of tolerance induction than the rejection process.

Acute Disease↗
PubMed2005

Frequency and clinical implications of development of donor-specific and non-donor-specific HLA antibodies after kidney transplantation.

The involvement of immunologic and nonimmunologic events in long-term kidney allograft failure is difficult to assess. The development of HLA antibodies after transplantation is the witness of ongoing reactivity against the transplant, and several studies have suggested that the presence of HLA antibodies correlates with poor graft survival. However, they have not discriminated between donor-specific (DS) and non-specific (NDS) antibodies. A total of 1229 recipients of a kidney graft, transplanted between 1972 and 2002, who had over a 5-yr period a prospective annual screening for HLA antibodies with a combination of ELISA, complement-dependent cytotoxicity, and flow cytometry tests were investigated; in 543 of them, the screening was complete from transplantation to the fifth year postgrafting. Correlations were established between the presence and the specificity of the antibodies and clinical parameters. A total of 5.5% of the patients had DS, 11.3% had NDS, and 83% had no HLA antibodies after transplantation. NDS antibodies appeared earlier (1 to 5 yr posttransplantation) than DS antibodies (5 to 10 yr). In multivariate analysis, HLA-DR matching, pretransplantation immunization, and acute rejection were significantly associated with the development of both DS and NDS antibodies and also of DS versus NDS antibodies. The presence of either DS or NDS antibodies significantly correlated with lower graft survival, poor transplant function, and proteinuria. Screening of HLA antibodies posttransplantation could be a good tool for the follow-up of patients who receive a kidney transplant and allow immunosuppression to be tailored.

Adult↗
PubMed2005

First total synthesis of cichorine and zinnimidine.

The first total synthesis of the phytotoxins cichorine and zinnimidine is described. The synthetic tactics involve the sequential connection of the dense and diverse functionalities on the aromatic nucleus followed by a Parham cyclization process, giving rise to the lactam unit embedded in the title compound framework.

Indoles↗
PubMed2005

Silent versus cranial giant cell arteritis. Initial presentation and outcome of 50 biopsy-proven cases.

BACKGROUND: The objective of the present study was to compare the silent form of giant cell arteritis (GCA) to the classic cephalic form of the disease. METHODS: We conducted a retrospective study based on a chart review of 50 consecutive, biopsy-proven GCA, recorded at a department of internal medicine. We sought to distinguish a silent form, defined by a prolonged inflammatory syndrome or fever of unknown origin with the absence of cephalic signs, polymyalgia rheumatica, or large artery involvement, from an overt "classic" cranial temporal arteritis. RESULTS: The prevalence of the silent form of GCA was 46% in our study. Abnormal temporal arteries were more frequent in the cephalic group. The silent GCA group had higher C-reactive protein levels (p<0.05), a higher platelet count (p<0.05), and lower serum albumin (p<0.05). There was no significant difference in temporal artery specimens in the two groups. Clinical relapses tended to be more frequent, and patients free of corticosteroids tended to be less frequent, in the cephalic group, though the difference was not statistically significant. CONCLUSIONS: The silent and cephalic forms of GCA could have distinct clinical and biological patterns and different outcomes. The limitation of our study was its retrospective design. Further studies are required to determine if this distinction is useful in treating GCA patients.

Journal Article↗
PubMed2004

A new route to aristocularine alkaloids: total synthesis of aristoyagonine.

A short and efficient synthesis of aristocularines, involving the sequential construction of phosphorylated 4-alkoxyisoindolinones, Horner-type reaction, and ultimate cyclization by diaryl ether coupling, is disclosed. The success of this new conceptual approach is demonstrated by the total synthesis of the aristocularine alkaloid aristoyagonine.

Cyclization↗
PubMed2004

Association of rapamycin and co-stimulation blockade using anti-B7 antibodies in renal allotransplantation in baboons.

BACKGROUND: Co-stimulation blockade has already been shown to induce transplantation tolerance in rodents, but until now has failed in large animal models. We therefore sought to investigate whether the addition of rapamycin to a co-stimulation blockade regimen could induce tolerance in baboon recipients of a renal allograft and to characterize the immunological characteristics of rejection. METHODS: Two baboons were used for a pharmacological and toxicological analysis and received anti-B7.1 and anti-B7 antibodies every other day for 60 days. Three groups of baboons underwent classical heterotopic renal allotransplantation; the first group received no treatment (control group; n = 2), the second received a combination of anti-CD80 and anti-CD86 monoclonal antibodies (mAbs) (B7 group; n = 4), and the third received the anti-B7 antibody treatment as above with an additional treatment of rapamycin (B7-Rapa; n = 4). Graft survival as well as immunological analyses were performed. RESULTS: Anti-B7 mAb monotherapy prolonged allograft survival in three out of four of the animals, one of whom survived rejection free for 87 days but died from a pulmonary embolism; the fourth animal died without rejection. The addition of rapamycin to the regimen did not prolong survival further; three of the four animals underwent early rejection whereas the fourth survived long term but eventually rejected at day 114. Whereas alloimmunization only occurred in this latter animal, rejection was always characterized by a substantial lymphocyte and monocyte infiltration, associated with a strong pro-inflammatory/cytotoxic mRNA accumulation in the anti-B7-treated animals, but to a lesser extent in the B7-Rapa group. T cells extracted and cloned from a biopsy taken at a stable post-transplant time showed a lower frequency of anti-donor alloreactivity in vitro than those extracted from a rejected tissue. Nevertheless, these non-responding clones failed to show regulatory activity in vitro. CONCLUSIONS: We thus confirm that blocking the CD28/B7 pathway by anti-B7 mAbs could prolong graft survival in baboons, but the addition of rapamycin was insufficient to induce tolerance.

Animals↗
PubMed2004

Initiation of gastrulation in the mouse embryo is preceded by an apparent shift in the orientation of the anterior-posterior axis.

BACKGROUND: It is generally assumed that the migration of anterior visceral endoderm (AVE) cells from a distal to a proximal position at embryonic day (E)5.5 breaks the radial symmetry of the mouse embryo, marks anterior, and conditions the formation of the primitive streak on the opposite side at E6.5. Transverse sections of a gastrulating mouse embryo fit within the outline of an ellipse, with the primitive streak positioned at one end of its long axis. How the establishment of anterior-posterior (AP) polarity relates to the morphology of the postimplantation embryo is, however, unclear. RESULTS: Transverse sections of prestreak E6.0 embryos also reveal an elliptical outline, but the AP axis, defined by molecular markers, tends to be perpendicular to the long axis of the ellipse. Subsequently, the relative orientations of the AP axis and of the long axis change so that when gastrulation begins, they are closer to being parallel, albeit not exactly aligned. As a result, most embryos briefly lose their bilateral symmetry when the primitive streak starts forming in the epiblast. CONCLUSIONS: The change in the orientation of the AP axis is only apparent and results from a dramatic remodeling of the whole epiblast, in which cell migrations take no part. These results reveal a level of regulation and plasticity so far unsuspected in the mouse gastrula.

Animals↗
PubMed2004

[Primary adrenal angiosarcoma].

We report the case of a 69-year-old man who presented with an adrenal angiosarcoma which had been discovered during prostatic adenocarcinoma staging. Twenty-two cases have been reported in the literature. All of them were of epithelioid type. Because of the epithelioid appearance and frequent expression of epithelial immunohistochemical markers, they can be confounded with adrenal carcinomatous metastases. Careful screening for vascular differentiation and immunohistochemistry with endothelial markers are essential for the diagnosis.

Adrenal Gland Neoplasms↗
PubMed2004

Sarcoidosis diagnosed in elderly subjects: retrospective study of 30 cases.

STUDY OBJECTIVE: This study investigated the clinical features and disease course of sarcoidosis diagnosed in patients > 70 years of age. METHODS: A retrospective analysis was made of cases treated at the University Hospital in Nantes, France, between 1986 and 2000. The diagnosis of sarcoidosis was confirmed histopathologically. Cases involving progressive cancer and active tuberculosis were excluded. RESULTS: Thirty white patients with sarcoidosis diagnosed after age 70 years (mean, 74 years) were included. An alteration of general health (asthenia and/or anorexia and/or weight loss) was frequent (53%) and characteristic of the systemic form of the disease. Dyspnea was a fairly common sign (23%). The intrathoracic form of sarcoidosis was most frequent (43.3%). Diagnosis was difficult and lengthy, and symptomatology was atypical. Accessory salivary gland biopsy was an important contributing factor to diagnosis (70.6% were positive). Oral corticosteroid therapy was often required (60.7%). The disease course was satisfactory overall (81.8% of cases), but only for 50% of patients in intrathoracic stage IV. CONCLUSIONS: The clinical presentation of sarcoidosis in elderly subjects is mainly characterized by an alteration of general health. Diagnosis is difficult and should include accessory salivary gland biopsy. Therapy frequently involves corticosteroids. Overall prognosis is similar to that for young subjects.

Aged↗
PubMed2003

Tolerance induction in rats, using a combination of anti-CD154 and donor splenocytes, given once on the day of transplantation.

BACKGROUND: Donor-specific tolerance induction remains an attractive objective that generates much research in the field of transplantation. Unfortunately, most of the protocols available involve pregraft conditioning, making these treatments incompatible with clinical applications. METHODS: LEW.1A rats were grafted with histoincompatible LEW.1W hearts. On the day of transplantation, recipients were treated with anti-CD40L combined with donor splenocytes. The hearts were evaluated for graft survival; cellular infiltrate and intragraft cytokines were determined using real-time reverse transcriptase-polymerase chain reaction. Tolerance induction was assessed by skin grafting and adoptive transfers. RESULTS: The combination of a single injection of anti-CD40L and donor splenocytes, given on the day of surgery, allowed 40% of cardiac allografts to survive long-term (mean survival time=66.3 day). The cellular composition or the extent of graft infiltrate was not modified but was associated with a massive decrease of proinflammatory cytokines expression within the graft. Long-term survivors accepted donor-matched skin grafts, and leukocytes harvested from these animals transferred tolerance into irradiated freshly grafted recipients. CONCLUSION: A combination of costimulation blockade and donor cells, given once at the time of transplantation, is sufficient to induce allograft tolerance in rats.

Animals↗
PubMed2003

Receptor activator of nuclear factor kappaB ligand (RANKL)/osteoprotegerin (OPG) ratio is increased in severe osteolysis.

Pathological osteolyses are considered a consequence of a disturbance in the mechanisms that govern the bone remodeling, mainly the communication between osteoclasts and osteoblasts. Osteoprotegerin (OPG) and receptor activator of NF-kappaB ligand (RANKL) are newly discovered molecules that play a key role in these communications. RANKL is essential for osteoclast differentiation via its receptor RANK located on the osteoclast membrane. OPG is a soluble decoy receptor that inhibits osteoclast differentiation through its binding to RANKL. The aim of this study is the analysis of the RANKL/OPG balance by complementary methods (semiquantitative reverse transcription-polymerase chain reaction, immunohistochemistry, and enzyme-linked immunosorbent assay) in human osteolysis associated to various bone etiologies (n = 60), tumoral (primitive, secondary) or not, compared to healthy tissues (n = 16). Results demonstrated that RANKL/OPG ratio was significantly increased in patients suffering from severe osteolysis compared to the control group and that this imbalance is involved in bone resorption mechanisms. In this study, OPG expression appears to reflect a protective mechanism of the skeleton to compensate increased bone resorption by inhibiting osteoclast formation and bone resorbing activity. Moreover, as revealed by immunohistochemistry, RANKL and OPG were colocalized in all of the tissues analyzed. To define the veracity of RANKL/OPG index in assessing and managing patients with severe osteolysis, an extended population of patients suffering from severe osteolysis must be now monitored.

Adolescent↗
PubMed2003

Cellular participation in delayed xenograft rejection of hCD55 transgenic pig hearts by baboons.

Delayed xenograft rejection (DXR) of pig organs by baboons currently represents the major obstacle to successful xenotransplantation. Although antibodies (Abs) are believed to play a fundamental role in this form of rejection, so far little is known concerning the potential cellular component. Biopsies taken during DXR of human CD55 transgenic pig hearts by non-treated (n = 2), alpha-Gal immunoadsorbed (n = 2), or immunosuppressed (n = 9) baboons were studied. The cellular element was explored by determining not only its phenotype by classical immunohistochemical techniques but also its activity in terms of cytokines, cytolytic enzymes and other mediators using quantitative reverse transcription polymerase chain reaction. All porcine xenografts underwent DXR; within 5 days in non-treated and immunoadsorbed animals but significantly delayed (6 to 29 days) in immunosuppressed animals. Cellular infiltration in non-immunosuppressed grafts consisted predominantly of monocytes/macrophages, CD8 cells and a few CD4 T-cells. The predominant baboon transcripts detectable were the proinflammatory cytokines interleukin1-alpha and tumor necrosis factor-alpha, the lymphokine interferon-gamma and the cytotoxic enzyme granzyme B. However, these cellular components were lacking in the immunosuppressed animals. Despite these differences, strong immunoglobulin M (IgM) and C5b-9 complement deposition was observed in all animals at rejection. Together our findings suggest that although the humoral response plays a predominant role in DXR through IgM Abs and complement activation, there is a clear cellular infiltrate in DXR in this model that is likely to contribute to rejection through a strong pro-inflammatory and cytotoxic environment, necessitating substantial immunosuppression for a prolonged graft survival.

Animals↗
PubMed2003

The effect of immunoglobulin immunadsorptions on delayed xenograft rejection of human CD55 transgenic pig kidneys in baboons.

Delayed xenograft rejection (DXR) remains a major obstacle in discordant xenotransplantation. As strategies of complement inhibition and xenogeneic natural antibody (Ab) removal have been shown to give prolonged xenograft survival, we endeavored to determine whether combining these two strategies would lead to an additive effect in terms of graft survival. The study was initiated with two groups, A and B, where group A received normal kidneys and group B received hCD55 transgenic kidneys. Both groups underwent pre-transplant (day-1) total immunoglobulin (Ig) immunoadsorption (IA) and received an immunosuppression of cyclophosphamide, cyclosporine A, mycophenolate mofetil and corticosteroids. Two subsequent groups (C and D) receiving hCD55 transgenic pig kidneys were then performed with an 'optimized' immunosuppression (Cyclophosphamide starting 1 day earlier) but only group D recipients were immunoadsorbed. Biopsies taken during the post-transplantation period were analyzed for Ab deposition, compliment activation and cellular infiltration. No hyperacute rejection was observed. In the initial immunoadsorbed groups A and B, all baboons underwent DXR, which started surprisingly early (day 5 in most cases. In the subsequent two groups, the immunoadsorbed group D baboons also underwent DXR, again as early as day 5. In contrast, group C baboons did not show any signs of DXR on their day 6 biopsy or at their time of death. Analysis of graft biopsies from the kidneys undergoing rejection or with stable function showed strong deposition of anti-Gal IgM in all cases whereas strong complement C5b-9 deposits were only observed in biopsies at rejection. Cellular infiltration consisted mostly of monocytes/macrophages, was more pronounced in biopsies taken at rejection and was associated with a pro-inflammatory environment involving interleukins 1alpha, 6 and 8. Our findings suggest non-specific Ig (anti-Gal and non-Gal Ig of all isotypes) IA or even incomplete IA in immunosuppressed baboon recipients of transgenic pig kidneys is detrimental to graft survival by being associated with an Ab and compliment driven rejection. We speculate that the IA were insufficient in terms of Ig depletion or frequency inducing an Ab rebound or that this total Ig depletion also removed components facilitating graft survival.

Animals↗
PubMed2003

[Kikuchi-Fujimoto disease: two cases].

Kikuchi-Fujimoto disease, or necrotizing histiocyte lymphadenitis, is a rare anatomo-clinical entity of unknown cause. The patients present painful cervical lymph nodes, fever, and a flu-like syndrome, but the spontaneous course is usually favorable in six months. We observed two cases within six months in our unit. Both patients improved rapidly after diagnostic adenectomy.

Adenoidectomy↗
PubMed2003

Temporal arteritis associated with systemic necrotizing vasculitis.

OBJECTIVE: To evaluate the clinical and laboratory characteristics of patients with systemic vasculitis associated with temporal artery involvement. METHODS: From a cohort of 120 patients fulfilling American College of Rheumatology criteria for temporal arteritis, we retrospectively identified 7 patients with systemic necrotizing vasculitis associated with histological temporal arteritis. RESULTS: Among the 7 patients, 2 had classic polyarteritis nodosa, one had unclassified systemic vasculitis, one had Wegener's granulomatosis (WG), and 3 had microscopic polyangiitis. The mean age of the patients was 70.2 years, and cranial symptoms revealed the disease in all but one patient. Temporal arteritis was generally associated with extracephalic manifestations suggestive of systemic vasculitis. Antineutrophilic cytoplasmic antibodies were positive in 3 of the 4 patients with small vessel vasculitis. Pathologically, the main temporal artery was involved in all but one patient, with inflammatory infiltrate of vasa vasorum and adventitia associated in 5 with small tributary involvement. Fibrinoid necrosis was rare, observed in 2 specimens; 2 patients with unclassified systemic vasculitis and WG had a classic giant cell arteritis (GCA) histologic pattern. Only one patient had exclusive involvement of small vessels, surrounding the spared main temporal artery. Muscle biopsies showed histopathological evidence of vasculitis in 2 patients, skin biopsy in one, and vein biopsy in the other. CONCLUSION: Temporal artery involvement in systemic necrotizing vasculitis was generally associated with extracranial clinical features suggestive of systemic vasculitis. Temporal artery biopsy is a simple tool for diagnosis of vasculitis, but the histopathological findings do not always discriminate between necrotizing vasculitis and classic GCA.

Aged↗
PubMed2002

Systemic vasculitis with lymphocytic temporal arteritis and Toxocara canis infection.

Vasculitis associated with helminthic infection is rare. We report a case of systemic negative antineutrophil cytoplasmic antibodies vasculitis associated with Toxocara canis infection documented by enzyme-linked immunosorbent assay and Western blot analysis. This case report is unusual because of lymphocytic temporal arteritis and renal involvement. The spontaneous remission of systemic vasculitis without use of steroids or immunosuppressive agents favors a close relationship between vasculitis and the parasite that is more than a coincidental association. To our knowledge, this is the first observation of temporal vasculitis associated with helminthic infection, extending the clinical spectrum of visceral larva migrans.

Aged↗