PubMed Health⌕ Search

Biomedical subjects

Marc André

Publications and source records attributed to Marc André.

At least 19 recordsLinked to original sources

CD8+HLA-DR+ T lymphocytes are increased in common variable immunodeficiency patients with impaired memory B-cell differentiation.

The recently proposed Piqueras classification of common variable immunodeficiency (CVID) patients is based on flow cytometric quantification of IgD class-switched and CD27 membrane-expressing mature blood B cells. But, many patients also have circulating T cells with immunophenotypic abnormalities, often associated with clinical complications, such as splenomegaly, autoimmune disease, lymphoid proliferation and/or granulomatosis. In 50 unselected CIVD patients, classified according to CD27 and IgD B-cell expression, we analyzed T-lymphocyte subsets according to their expression of HLA-DR and intracellular perforin and/or granzyme B in CD8+ T lymphocytes, CCR7 and CD45RA. CD3+DR+ T-lymphocyte percentages, predominantly CD8+DR+, were significantly higher in patients with clinical complications. MB0 classified patients, characterized by fewer CD27+ B cells, had higher percentages of CD8+DR+ T lymphocytes expressing perforin and/or granzyme with a differentiated effector (CCR7- and CD45RA+) phenotype. In contrast, MB2 patients (with normal CD27+ and IgD- B cells) were free of clinical complications and showed no signs of T-cell activation. MB1 patients (normal CD27+ numbers but fewer IgD- B cells) were either clinically normal or had complications. Combining the set of markers described herein might better define homogeneous groups of patients for etiological studies and clearly segregate patients with clinical complications.

Adolescent↗

[Outcome of oncocytomas diagnosed by percutaneous renal biopsy].

OBJECTIVE: Renal oncocytoma is a benign tumour that is usually diagnosed postoperatively. Its natural history is poorly defined. We studied the outcome of patients with renal oncocytoma diagnosed by percutaneous biopsy and not operated. MATERIAL: From January 1998 to April 2004, on a series of 148 renal tumour biopsies performed in our centre, 15 showed oncocytoma. The initial treatment was non-surgical. We report the follow-up of these patients and the course of these oncocytomas. The mean follow-up was 404 +/- 20.9 months. RESULTS: The mean age of these patients at diagnosis was 57.6 +/- 14.4 years and the mean tumour diameter was 3.49 +/- 2.43 cm with a mean volume of 62.3 +/- 135.4 cm3. Six of these 15 patients were operated: 4 total nephrectomies and 2 partial nephrectomies. The indications for surgery were the initial tumour volume (n = 1), tumour growth > 0.5 cm/year (n = 4) and the patient's preference (n = 1). Operated patients were younger (45.5 +/- 11.1 years vs 65.6 +/- 10.3 years) and had larger tumours at diagnosis (50 +/- 30.1 mm vs 27.3 +/- 10.5 mm). All 9 patients treated by watchful waiting were asymptomatic. CONCLUSION: The natural history of oncocytomas appears to be a more or less rapid increase in size. Treatment can be conservative. The initial tumour volume or rapid tumour growth are indications for resection. Partial nephrectomy, when allowed by the size and site of the tumour is currently the technique of choice.

Adenoma, Oxyphilic↗

Altered dendritic cell distribution in patients with common variable immunodeficiency.

Recent data suggest a critical role for dendritic cells (DCs) in the generation of immunoglobulin-secreting plasma cells. In the work reported herein, we analyzed the frequency of peripheral blood plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) in a cohort of 44 adults with common variable immunodeficiency (CVID) classified according to their CD27 membrane expression status on B cells. A deep alteration in the distribution of DC subsets, especially of pDCs, in the peripheral blood of CVID patients was found. Patients with a reduced number of class-switched CD27+IgD-IgM- memory B cells and patients with granulomatous disease had a dramatic decrease in pDCs (P = 0.00005 and 0.0003 vs controls, respectively) and, to a lesser extent, of mDCs (P = 0.001 and 0.01 vs controls, respectively). In contrast, patients with normal numbers of switched memory B cells had a DC distribution pattern similar to that in controls. Taken together, our results raise the possibility that innate immunity contributes to pathogenesis in CVID.

Adolescent↗

Lutein transport by Caco-2 TC-7 cells occurs partly by a facilitated process involving the scavenger receptor class B type I (SR-BI).

The carotenoid lutein is thought to play a role in the human eye and to protect against age-related macular degeneration. Lutein transport in the human intestine has not been characterized. We examined lutein transport processes using Caco-2 TC-7 monolayers as a model for human intestinal epithelium. Purified lutein was mixed with phospholipids, lysophospholipids, cholesterol, mono-olein, oleic acid and taurocholate to obtain lutein-rich mixed micelles that mimicked those found under physiological conditions. The micelles were added to the apical side of Caco-2 TC-7 cell monolayers for 30 min or 3 h at 37 degrees C. Absorbed lutein, i.e. the sum of lutein recovered in the scraped cells and in the basolateral chamber, was quantified by HPLC. Transport rate was measured (i) as a function of time (from 15 to 60 min), (ii) as a function of micellar lutein concentration (from 1.5 to 15 microM), (iii) at 4 degrees C, (iv) in the basolateral to apical direction, (v) after trypsin pretreatment, (vi) in the presence of beta-carotene and/or lycopene, (vii) in the presence of increasing concentrations of antibody against SR-BI (scavenger receptor class B type 1) and (viii) in the presence of increasing concentrations of a chemical inhibitor of the selective transfer of lipids mediated by SR-BI, i.e. BLT1 (blocks lipid transport 1). The rate of transport of lutein as a function of time and as a function of concentration was saturable. It was significantly lower at 4 degrees C than at 37 degrees C (approx. 50%), in the basal to apical direction than in the opposite direction (approx. 85%), and after trypsin pretreatment (up to 45%). Co-incubation with beta-carotene, but not lycopene, decreased the lutein absorption rate (approx. 20%) significantly. Anti-SR-BI antibody and BLT1 significantly impaired the absorption rate (approx. 30% and 57% respectively). Overall, these results indicate that lutein absorption is, at least partly, protein-mediated and that some lutein is taken up through SR-BI.

Binding, Competitive↗

Molecular mechanisms of the naringin low uptake by intestinal Caco-2 cells.

Naringin, the main flavanone of grapefruit, was reported to display numerous biological effects: antioxidant, hypocholesteremic, anti-atherogenic and favoring drug absorption. Naringin absorption mechanisms were studied in Caco-2 cells (TC7 clone). We investigated the possible involvement of several membrane transporters implicated in polyphenolic compounds intestinal transport (sodium-dependent glucose transporter 1, monocarboxylate transporter, multidrug-associated resistance proteins 1 and 2, and P-glycoprotein). Naringin was poorly absorbed by Caco-2 cells, according to its low value of apparent permeability coefficient (P(app) = 8.1 +/- 0.9 x 10(-8) cm/s). In the presence of verapamil, a specific inhibitor of P-glycoprotein, cellular uptake was increased by almost threefold after 5 min, and P(app) was doubled after 30 min. Our results indicated the involvement of P-glycoprotein, an ATP-driven efflux pump, capable of transporting naringin from the Caco-2 cell to the apical side. This phenomenon could explain, at least in part, the low absorption of this flavanone at the upper intestinal level.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Spontaneous pneumothorax in Wegener granulomatosis.

Spontaneous pneumothorax in Wegener granulomatosis (WG) is uncommon. Three cases of pneumothorax that occurred early in the course of this vasculitis are reported. In the first patient, the disorder was disclosed by a pyopneumothorax. In the second patient, a rupture of the subpleural cavitary nodule into the pleural space was observed. In the third patient, the pneumothorax was discovered at the same time as a pulmonary hemorrhage. The three patients improved with immunosuppressive therapy. In WG, the pulmonary nodules are predominantly in the subpleural location, which entails the risk of pneumothorax and therefore require particular attention.

Granulomatosis with Polyangiitis↗

[Renal oncocytoma associated with renal cell carcinoma].

Renal oncocytoma is a benign tumour that can be associated with renal cell carcinoma in rare genetic syndromes. The authors report the case of a 62-year-old patient with no medical history, in whom assessment of low back pain in 1999 demonstrated a 40 mm tumour of the lower pole of the left kidney. Percutaneous needle biopsy of the tumour demonstrated oncocytoma confirmed by Hale's stain. Follow-up ultrasound demonstrated an increase in size (88 mm) and a nine-fold increase in volume over four years (210 cm3 in April 2003). Surgery was indicated in view of the rapid increase of the tumour volume. Histological examination of the operative specimen demonstrated a combination of oncocytoma and Fuhrman grade III renal cell carcinoma.

Adenoma, Oxyphilic↗

[Tubulopapillary tumours of the kidney: prognostic value and therapeutic implications of the distinction between type 1 and type 2 based on a series of 58 cases].

OBJECTIVE: The purpose of this study was to demonstrate the prognostic value of subdivision of tubulopapillary tumours into 2 histological subtypes and to discuss the therapeutic implications. MATERIALS AND METHODS: This was a single-centre retrospective study of 58 cases from a series of 414 patients operated for renal cancer between 1988 and 2001 based on review of histology slides (biopsies and operative specimens). The radiological assessment was based on ultrasound reports and review of CT scans. Karyotypes were described by cytogenetic analysis. RESULTS AND DISCUSSION: Tubulopapillary tumours represented 14% of all kidney tumours with a male prevalence of 77% and a mean age of 56.5 years. The overall mean follow-up was 62.6 months. Treatment consisted of 25 right radical nephrectomies, 29 left radical nephrectomies and 4 partial nephrectomies. 84% of tumours were low-grade and 80% were low stage T1 or T2. Multifocal lesions were observed in 31% of cases. Synchronous bilateral lesions were observed in 12% of cases. The 5-year survival was 95% and the 10-year survival was 87%, correlated with stage, grade, tumour diameter, presence of necrosis and low enhancement. According to the data reported by Delahunt, 2 subtypes can be distinguished: Type I tumours (75%) with low grade and low stage were correlated with a high rate of multifocal lesions (30%) with a genetic predisposition. Type 2 tumours (25%), usually unifocal, were correlated with a higher grade and stage, confirmed by their poorer prognosis. Biopsy allows a distinction of the type and grade of the tumour. CONCLUSIONS: In our series, for equivalent mean tumour diameters (55 mm), tubulopapillary tumours treated by radical nephrectomy had a good prognosis regardless of their subtype. Classification of the tumour by biopsy prior to surgery could have implications for therapeutic management. For type 1 tubulopapillary tumours identified on preoperative biopsy, we propose radical nephrectomy due to the high risk of multifocal lesions (30%). Although partial nephrectomy may be indicated for type 1 tubulopapillary tumours less than 4 cm, the patient must be informed about the risk of recurrence and the importance of long-term follow-up. Studies including a larger number of patients must be conducted to compare the survival associated with type 2 tumours compared to that of the classical histological subtype.

Carcinoma, Papillary↗

Antineutrophil cytoplasmic antibodies of IgA class in neutrophilic dermatoses with emphasis on erythema elevatum diutinum.

OBJECTIVE: To evaluate the prevalence of IgA and IgG antineutrophil cytoplasmic antibodies (ANCAs) in erythema elevatum diutinum in comparison with 2 other groups of neutrophilic dermatoses: Sweet syndrome and pyoderma gangrenosum. DESIGN: Detection of IgA and IgG ANCAs in the serum of patients with neutrophilic dermatoses and characterization of the previously known antigenic targets. SETTING: All serum was analyzed without knowledge of diagnosis in the Immunology Department, Pitié-Salpêtrière Hospital, Paris, France. PATIENTS: Ten patients with erythema elevatum diutinum, 10 with Sweet syndrome, 10 with pyoderma gangrenosum, and 10 healthy volunteers. MAIN OUTCOME MEASURES: IgA and IgG ANCAs were sought by indirect immunofluorescence with ethanol and formaldehyde-fixed human neutrophil preparations as the substrate. Enzyme-linked immunosorbent assays were further performed for antigen characterization. RESULTS: IgA ANCAs were observed in 60% and IgG ANCAs in 10 (33%) of the patients. All patients with erythema elevatum diutinum had IgA ANCAs. IgA fluorescence in formaldehyde-fixed neutrophils was restricted to those from patients with erythema elevatum diutinum. Enzyme-linked immunosorbent assays disclosed no single predominant target, and antigens remained largely undetermined in erythema elevatum diutinum. CONCLUSIONS: The ANCAs, particularly of IgA class, may prove to be a helpful paraclinical marker in erythema elevatum diutinum and an interesting perspective for understanding the pathophysiology of the disease. The nature of the unidentified targets and the pathogenicity of ANCAs, however, remain to be assessed.

Adolescent↗

Ovarian vein thrombosis in the antiphospholipid syndrome.

Ovarian vein thrombosis (OVT) is an unusual condition mainly observed during the postpartum period. It has not been reported to date in the antiphospholipid syndrome. Two female patients with definite antiphospholipid syndrome, ages 33 years and 73 years, were diagnosed as having OVT by computed tomography (CT) scan, according to the radiologic criteria described by Zerhouni et al. In 1 of the women, the left vein was affected by OVT, while in the other woman, the right vein was affected. One of the patients had a pulmonary embolism; the diagnosis of OVT was established after she underwent a cesarean section and a right atrium thrombectomy. The other patient had no vascular manifestations. OVT was asymptomatic in both patients. Searches for associated thrombophilic states yielded negative results. With the continuation of anticoagulation therapy, the 2 patients have remained in good condition. Resolution of the OVT was observed in the patient who underwent a CT scan during followup. To our knowledge, this is the first report of OVT occurring in the antiphospholipid syndrome. Given that it may develop in the absence of pelvic clinical manifestations, this complication may be underdiagnosed.

Abdominal Pain↗

[Kidney tumors].

Explore the source record for details and available documents.

Humans↗

Second cancers and late toxicities after treatment of aggressive non-Hodgkin lymphoma with the ACVBP regimen: a GELA cohort study on 2837 patients.

The survival of patients with aggressive non-Hodgkin lymphoma (NHL) is increasing, but the incidence of secondary cancer and late toxicity is poorly defined for those treated with cyclophosphamide-hydroxydaunomycin/doxorubicin-Oncovin-prednisone (CHOP)-like chemotherapy. From February 1984 to January 1998, 2837 patients with aggressive NHL received the control-arm chemotherapy adriamycin-cyclophosphamide-vindesine-bleomycin-prednisone (ACVBP) in 3 consecutive Groupe d'Etude des Lymphomes de l'Adulte (GELA) studies. With a median follow-up time of 74 months, the 5-year overall and event-free survival rates were 60% and 52%. Two hundred two occurrences of nonneoplastic late toxicity were reported, resulting in a 5.35% cumulative probability of incidence at 7 years. Eighty-one second tumors developed, for which the 7-year cumulative incidence rate was 2.75%; 64 were solid tumors, and 17 were hematologic malignancies. In multivariate analysis, age was the only risk factor for the second development of cancer. Epidemiologic analysis allowed a comparison of this NHL group with the general population. Considering all tumors, no excess of second cancer was observed. In the male population, however, there was an excess of lung cancer (standardized incidence ratio [SIR], 2.45; P <.001) and myelodysplastic syndrome/acute myelocytic leukemia (MDS/AML) (SIR, 5.65; P =.006), and in the female population there was an excess of MDS/AML (SIR, 19.9; P <.001). With a long follow-up, the ACVBP regimen was highly effective for the treatment of aggressive NHL. Increases occurred in secondary MDS/AML and in lung cancer among men.

Adolescent↗

Effects of cyclosporine-A on brain lipids and apolipoprotein E, J gene expression in rats.

Cyclosporine-A, an immunosuppressive agent, is known to produce complications such as seizures and encephalopathies. It alters peripheral lipid metabolism, but its effect on brain lipid metabolism is unknown. Alterations in brain cholesterol and phosphatidylcholine levels, as well as in apolipoproteine E and J gene expression, are reportedly involved in epilepsy and Alzheimer's disease (AD) and were here evaluated in rats following administration of cyclosporine-A for 3 weeks. Unesterified cholesterol and phospholipid brain levels were decreased by cyclosporine whereas apolipoprotein E and J mRNA levels were not altered in hippocampus or in cortex. These alterations in brain lipid metabolism are not similar to that reported in epilepsy or AD and exclude the involvement of apolipoprotein E and J over-expression in cyclosporine-mediated neurological disorders.

Animals↗

Increased tissue protein synthesis during spontaneous inflammatory bowel disease in HLA-B27 rats.

Inflammatory bowel diseases (IBDs) are associated with an increased whole-body protein turnover. In certain drug-induced experimental models of IBD, disturbances of protein synthesis in tissues have been reported recently, but it is unclear if similar disturbances occur in other chronic intestinal diseases. Therefore we investigated changes in protein synthesis in different tissues of HLA-B27 (human leucocyte antigen B27) transgenic rats that develop spontaneously chronic inflammation, with major involvement of the colon. Protein synthesis rate in HLA-B27 rats was shown to be higher in nine different tissues compared with control (Fisher 344) rats. The absolute rate of protein synthesis was highly stimulated at the main inflammatory site (+290% in the colon). However, liver, muscle and skin appeared to be major contributors to the increased protein synthesis observed at the whole-body level. Despite the increased protein synthesis, HLA-B27 rats presented a marked atrophy of muscles, which suggests an increased proteolysis. These results contrast with metabolic disturbances described in acute inflammation and colitis induced by drugs (i.e. dextran sodium sulphate). The present study suggests that the modifications of protein metabolism are strongly influenced by the type of the inflammatory diseases and thus by the underlying mechanisms, which result in different metabolic adaptations and specific nutritional requirements.

Acute Disease↗

Phase III randomized study comparing 5 or 10 microg per kg per day of filgrastim for mobilization of peripheral blood progenitor cells with chemotherapy, followed by intensification and autologous transplantation in patients with nonmyeloid malignancies.

BACKGROUND: It is not known whether increasing the dose of filgrastim after mobilizing chemotherapy improves collection of peripheral blood progenitor cells (PBPC) and leads to faster hematopoietic engraftment after autologous transplantation. STUDY DESIGN AND METHODS: A randomized, open-label, multicenter trial was carried out in patients with breast cancer, multiple myeloma, and lymphoma, in which patients were randomized to receive 5 or 10 microg per kg per day of filgrastim after standard chemotherapy to mobilize PBPCs. After high-dose chemotherapy, the components from the first two leukapheresis procedures were returned, and all patients received 5 microg per kg day of filgrastim after transplantation. RESULTS: A total of 131 patients were randomized, of whom 128 were mobilized (Group A, 5 microg/kg, n = 66; Group B, 10 microg/kg, n = 62) and 112 were transplanted. Only six patients were not transplanted because of insufficient CD34+ cell numbers. The median number of CD34+ cells collected in the first two leukapheresis procedures tended to be higher in Group B than in Group A (12.0 vs. 7.2 x 10(6)/kg, NS), but after transplantation there was no significant difference in median times to platelet (9 days in both groups) or neutrophil (8 days in both groups) engraftment or the number of platelet transfusions (three in both groups). A subsequent subgroup analysis separating patients transplanted after first- or second-line chemotherapy also showed no measurable impact of filgrastim dose on the median CD34+ cell yield or on platelet engraftment in either subgroup. CONCLUSION: PBPC mobilization with chemotherapy and 5 microg per kg of filgrastim is very efficient, and 10 microg per kg of filgrastim does not provide additional clinical benefit.

Adult↗