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Biomedical subjects

J F Lesesve

Publications and source records attributed to J F Lesesve.

At least 19 recordsLinked to original sources

Osteopetrotic mouse stroma with thrombopoietin, c-kit ligand, and flk-2 ligand supports long-term mobilized CD34+ hematopoiesis in vitro.

OP-9 cells are stromal cells derived from macrophage colony-stimulating factor (M-CSF)-deficient osteopetrotic mice. To evaluate the OP-9 capability to sustain long-term hematopoiesis, we reported the expansion of granulocyte colony-stimulating factor (G-CSF)-mobilized human peripheral blood (PB) CD34(+) cells in co-culture with murine OP-9 and MS-5 stromal cells, either transfected with various combinations of adenovectors (Ad) expressing c-kit ligand (KL) (either soluble or transmembrane form), thrombopoietin (TPO), flt-3/flk2 ligand (FL), and granulocyte-macrophage (GM)-CSF or with weekly addition of these cytokines. Expression of TPO as well as association of TPO, FL, and KL increased progenitor cell and week-6 cobblestone area forming cell (CAFC) production in all stromal co-cultures. Similar progenitor expansion was obtained by weekly addition of soluble cytokine. Five weeks of co-culture with OP9 and TPO, FL + KL resulted in the greatest expansion of progenitor cells and week-6 CAFC as measured by secondary assay on MS-5. In contrast to MS-5 and TPO or TPO + FL + KL cultures where hematopoiesis declined by week 4, progenitor as well as week-6 CAFC expansion continued for over 3 months in TPO + FL + KL OP9 cocultures. This was associated with decrease of CD14(+) macrophage production. The addition of human macrophage (M)-CSF or CD14(+) cells to the co-culture decrease progenitor and stem cell expansion; however, murine M-CSF to OP-9 co-cultures did not decrease progenitor expansion. High levels of stromal-derived factor-1 (SDF-1) production by MS-5 and low or absent production by OP-9 may account for stem cell adhesion and CAFC formation in the former cultures and the predominance of stem and progenitor cells in the nonadherent fraction in the latter cultures.

Adenoviridae↗

Brown Norway rat ovalbumin-specific immunoglobulin E antibodies increase the human basophil expression of CD63 marker.

Anaphylactic shock is an immunoglobulin E (IgE)-dependent hypersensitivity. Biological tests like leucocyte histamine release (LHR) and human basophil activation (HBA), frequently used in human allergy, reflect both the amount of IgE fixed on cells and the cellular reactivity. To assess whether serum-specific IgE from Brown Norway (BN) rats prepared for ovalbumin (OVA)-induced anaphylactic shocks can activate human basophils which has a potential interest in experimental allergy: such a test could rapidly assert an IgE sensitization in laboratory animals genetically T-helper 2 (Th2)-predisposed. Rats (n = 39) were immunized three times (day 0, day 5 and day 21) with OVA injected subcutaneously. One week after the third immunization, a shock was induced with an intravenous (i.v.) bolus of OVA. Sensitization was assessed by passive cutaneous anaphylaxis (PCA) test and dosages of serum IgE antibodies anti-OVA by enzyme-linked immunosorbent assay. Blood basophils were counted before and during the shock. Before the shock induction (at day 21), an LHR test was performed on rat blood, and human basophils were sensitized with rat sera. HBA was demonstrated by the increase in the percentage of cells expressing CD63 antigen membrane, measured by flow cytometry. Twenty-one days after the first subcutaneous (s.c.) immunization, the rat serum induced a significant HBA. HBA was observed neither with the same serum previously heated nor with the serum from nonimmunized rats (NIRs). OVA-specific IgEs were significantly increased in immunized rat (IR) serum. The PCA test was negative when the serum was previously heated (56 degrees C). We never observed any circulating basophils, and LHR test was negative. After OVA i.v. administration, all IRs died rapidly. HBA testing strongly suggests a mediation by specific IgE in the increase of CD63 in BN rats. Thus, HBA test seems useful in assessing whether an experimental allergy was induced in animals genetically predisposed to an immune response, Th2-mediated, like BN rat. We also conclude that rat basophil activation does not participate in the histamine release during anaphylactic shock in sensitized BN rats.

Anaphylaxis↗

[Changes in hemogram parameters in infections].

PURPOSE: Leukocytosis is considered as an argument for infection. We have compared leukocytosis with the other data available with the white blood cell count. METHODS: White blood cell counts obtained from 187 patients (age: 18 to 81 years), admitted to an emergency room for abdominal pain, were analysed using an automate (Bayer Technicon H2, Dublin, Ireland), and compared with matched healthy subjects. The patients were classified into two groups: diseases of the biliary or of the urinary tract, and subsequently in two subgroups: infectious diseases (angiocholitis, cholecystis, pyelonephritis) or non-infectious diseases (hepatic and nephritic colic). RESULTS: Leukocytes and neutrophils were significantly increased, and eosinophils significantly decreased in all subjects by comparison with controls. These abnormalities were more important in infected patients. Lymphocytes were significantly decreased in infectious disease. For predicting infection, sensitivity and specificity of leukocytosis (> 1,000/mm3) were respectively 66% and 56%, while that of eosinopenia (< 100/mm3) were respectively 91% and 38%, and that of lymphopenia (< 1,200/mm3) respectively 58% and 73%. The probability of infection was less than 3% when neutrophils were less than 7,000/mm3, and eosinophils and lymphocytes respectively more than 100/mm3 and 1,200/mm3. CONCLUSION: This study shows that leukocytosis, eosinopenia or lymphopenia are poor indicators of infection, when considered alone or in combination. However, eosinopenia and lymphopenia appear as better criteria of infection than leukocytosis. A detailed analysis of the white blood cell count allows the exclusion of infection with an acceptable risk of error.

Acute Disease↗

Increase of high fluorescence reticulocytes indicates mobilization of peripheral stem cells in children recovering from aplasia after chemotherapy or bone marrow transplantation.

Enumeration of CD34 + cells is the standard assay procedure for optimization of peripheral blood stem cell harvesting. High fluorescence reticulocytes (HFR) have been shown to signal a rebound in haematopoiesis after chemotherapy. The aim of this study was to evaluate HFR determination, as compared to CD34 + cell counts and CFU-GM, as a potential predictor of PBSC counts after recovery from chemotherapy and/or bone marrow transplantation. Twenty-five paediatric patients undergoing intensive courses of chemotherapy and 9 undergoing bone marrow auto or allografts were investigated. In most of our cases, HFR recovered at the same time or earlier than CD34 + cells. Similarly, the rise in HFR preceeded the CFU-GM peak in most of these cases. In no case did we observe a CFU-GM peak without a rise in HFR%. In our experience, the daily relative HFR increase may be used to predict the optimal time for mobilization of stem cells and was therefore of value clinically to confirm the timing of apheresis.

Adolescent↗

Leukaemic small cell variant anaplastic large cell lymphoma during pregnancy.

The history of a 28-year-old woman with anaplastic large cell lymphoma (ALCL) in the first trimester of her pregnancy is reported. Investigations allowed to diagnose a T-cell CD30 positive ALCL, which appearance is rare during pregnancy. Moreover, the atypical lymphoid cells were found in the peripheral blood and were predominantly small to medium sized with nuclear irregularities and cytoplasmic azurophilic granules, which allowed the hypothesis of leukaemic presentation of a small cell variant ALCL. A variant of the t(2:5)(p23:q35) was found [del(2)(p22)]. The patient died shortly after diagnosis.

Adult↗

Enterovirus-associated haemophagocytic syndrome in a neonate.

A 3-d-old neonate presented with fever, hepatosplenomegaly, coagulopathy, thrombopenia and anaemia. Secondary haemophagocytic lymphohistiocytosis was suspected, as persistent cytopenias were associated with hypofibrinogenaemia, haemophagocytosis in bone marrow and decreased NK cell. There was no positive family lymphohistiocytosis history or parental consanguinity. Bacterial investigation proved negative. The diagnosis of enterovirus maternofoetal infection was carried out. The infant's condition improved with symptomatic therapy from day 7. Follow up at 1 y was normal without relapse. This is the first report of a neonatal enteroviral infection that was responsible for excessive macrophage activation.

Enterovirus Infections↗

PreB1 (CD10-) acute lymphoblastic leukemia: immunophenotypic and genomic characteristics, clinical features and outcome in 38 adults and 26 children. The Groupe dEtude Immunologique des Leucémies.

The less differentiated stage (CD10-) of B-lineage acute lymphoblastic leukaemia (ALL) described as preB1-ALL in the GEIL nomenclature, accounts for less than 10% of ALL. It is classically considered to be associated with translocation (4;11)(q21;q23), and to have a poor prognosis. We report an extensive immunophenotypic, genomic and clinical study of a series of 64 preB-1 ALL patients, representing 6.3% of a cohort of consecutive ALLs. The engagement of preB1-ALL cells in the B-lineage was confirmed by their B-lineage score, equal to or higher than 2. In addition, more than 90% of the cases tested showed rearranged IGH genes. Translocation (4;11) was the most frequent karyotypic anomaly seen, but only accounted for 24% of the preB1-ALL cases tested. Expression of the myeloid associated antigen CD15 was also found with high incidence in this subset. Clinical and biological features at presentation showed more significant differences between preB1- and T-ALL than between preB1- and preB2-ALL (CD10+). However, outcome characteristics of the 22 children with preB1-ALL confirmed the worse prognosis of this entity.

Adolescent↗

Therapy-related acute myeloid leukemia with t(8;21) in a child with previous Ewing's sarcoma.

Cases of secondary acute myeloid leukemia (AML) occurring after treatment for an Ewing's sarcoma are uncommon. Therapy-related AML with t(8;21) translocation is an entity which has been well characterized. A case of AML-2 with t(8;21) and t(3;15) occurring 4 years after treatment for an Ewing's sarcoma with cyclophosphamide, doxorubicin, vincristine, dactinomycin, and radiotherapy, is reported. Autologous bone marrow transplantation was performed during second remission, 23 months after diagnosis. Reverse transcriptase polymerase chain reaction of the AML1/ETO fusion gene product was performed in order to monitor the quality of the remission. The patient currently remains in remission 24 months after the bone marrow transplantation.

Antineoplastic Combined Chemotherapy Protocols↗