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Biomedical subjects

A Falkenrodt

Publications and source records attributed to A Falkenrodt.

At least 19 recordsLinked to original sources
PubMed1995

Application of flow cytometry in toxinology: pathophysiology of human polymorphonuclear leukocytes damaged by a pore-forming toxin from Staphylococcus aureus.

The pore-forming activity of leukocidin (PVL) secreted by Staphylococcus aureus has been investigated on human white cells by flow cytometry techniques. This two-component toxin induced morphological modifications of neutrophils and monocytes as detected by forward light scattering measurements, but was inactive on lymphocytes. These modifications were the consequence of pore formation through the cell membrane leading to its permeabilization. In the absence of calcium, PVL formed pores large enough to allow ethidium ions to penetrate the cells and become fluorescent by intercalating nucleic acids. In the presence of calcium, the pores were too small for ethidium entry but allowed an influx of calcium as shown by the increase in fluorescence of Fluo-3 loaded in the cells. This increase in intracellular calcium concentration induced the activation of neutrophils by PVL as shown by the liberation of their granule content measured by a decrease in side light scattering. Furthermore, ethidium fluorescence was used to discriminate the cells sensitive to PVL, and the analysis of differentiated HL-60 cells and cells obtained from a case of chronic myeloid leukemia led to the conclusion that myeloid cells become sensitive to PVL during differentiation to the metamyelocyte stage.

Bacterial Toxins↗
PubMed1995

T-cell repertoire of normal, rejected, and pathological corneas: phenotype and function.

The specific immune mechanisms of corneal graft rejection are not completely understood. Recently, the technique of growing T-cell lines from rejected allografts using recombinant IL-2 has enabled the cells involved in allograft rejection to be recognized. In the present study, this method was applied for the extraction and propagation of T lymphocytes from rejected, normal, and diseased corneas. T-cell lines could successfully be grown from rejected and normal corneas, but not from corneas with keratoconus or pseudophakic bullous keratopathy. The phenotypic repertoire of the grown cells was studied by FACS scan analysis. Rejected corneas were invaded by a mixture of activated CD4+ and CD8+ T-cell lines, with one population being predominant. In normal corneas only activated CD8+ cells with cytotoxic function were cultured. No cells were obtained from diseased corneas. The in vitro function of cell lines was assessed by primed lymphocyte testing. The present study shows that the technique of propagating invading T-cell lines from organ grafts can be applied to human corneas, offering a new approach to understanding the immunological mechanisms occurring inside this immune tissue.

Antibodies, Monoclonal↗
PubMed1994

An optimized method for routine HLA-B27 screening using flow cytometry.

Flow cytometry and monoclonal antibodies are promising tools for HLA-antigen detection. Previous approaches have been hampered by the lack of a carefully standardized system for calibration and sample analysis. A new system for HLA-B27 screening was developed using a FACScan flow cytometer, software for automated calibration and analysis, calibration beads, and the anti-HLA-B27-FITC/anti-Leu4-PE (CD3) monoclonal antibodies. The median fluorescence channel result for the HLA-B27-FITC signal of CD3+ T lymphocytes is compared to a decision marker. Values lower than this threshold are read as HLA-B27 negative and those above are recommended for retesting with the classic microcytotoxicity assay on the presumption of HLA-B27 positivity. The anti-HLA-B27 antibody reacts with all six HLA-B27 subtypes and shows a weaker binding to HLA-B7. The screening test results were compared with those from the microcytotoxicity assay for HLA-typing in studies involving several European centers. The observed sensitivity was 100% (95% Cl:98.6-100) and the specificity was 97.4% (95% Cl: 96.4-98.3). Other performance studies verified the reproducibility and reliability of results obtained with the screening system.

Anticoagulants↗
PubMed1993

CD2 + CD19 + acute lymphoblastic leukaemia in 16 children and adults: clinical and biological features. Groupe d'Etude Immunologique des Leucémies (G.E.I.L.).

A small population of CD2 + CD19 + lymphoid cells have been suggested to be common lymphoid progenitors. CD2 + CD19 + biphenotypic ALL account for less than 2% of ALL. We analysed the clinical and laboratory features of a series of 16 patients with CD2 + CD19 + ALL. The incidence of tumoural syndrome was comparable to a previously published series of pre B-ALL but significantly different from that of T-ALL. The mean age of the 11 children of this series was 101 +/- 46 months, and differed significantly from that of children with pre B-ALL (P < 0.01). Complete remission was obtained for all patients except two adults. Only three relapses have been observed. Regardless of the presence of CD2 +, the 16 ALL could be classified as pre B-ALL, according to the nomenclature used by the GEIL. Nine samples could be analysed by Southern blotting. Seven had rearranged IGH genes, usually on both chromosomes. IGK rearrangement was observed in three cases. Only one case had rearranged both TCRG and TCR beta. The patterns observed here and those reported previously follow that of the pre B-ALL which confirms the engagement of most CD2 + CD19 + biphenotypic ALL in the B-lineage.

Adult↗
PubMed1993

A significant percentage of normal T lymphocytes express HLA-DP in the peripheral blood.

HLA-DP expression has been widely investigated on T lymphocytes activated under different conditions. In the present study, a double staining procedure was used in flow cytometric experiments to define DP expression on normal peripheral blood T lymphocytes. In about two-thirds of the case analyzed, DP was expressed on a higher percentage of normal peripheral T lymphocytes than DR was. This was particularly true for 1 of the 16 cases investigated in which the percentage of T lymphocytes expressing DP was 46% and in which DP expression was mainly the prerogative of CD8+ and CD56+ lymphocytes.

Antigens, CD↗
PubMed1993

Characteristics of pro-T ALL subgroups: comparison with late T-ALL. The Groupe d'Etude Immunologique des Leucémies.

A group of 30 acute lymphoblastic leukemias (ALL) with the early pro-T phenotype CD7+/cCD3+/CD1-/CD3-/CD4-/CD8-were identified among 103 newly diagnosed ALL with T-lineage markers (T-ALL). Pro T-ALL was more often observed in adults, and showed a lower incidence of hyperleukocytosis than more mature T-ALL. Mediastinal masses and polar acid phosphatase positivity in blast cells were however observed with the same frequency in pro T-ALL and late T-ALL, and rearrangements of both T-cell receptor (TCR) beta and gamma genes were observed in half the pro T-ALL cases tested. The expression of CD34, DR, and myeloid (My) markers was significantly more frequent in pro T-ALL than in late T-ALL, and these three features were strongly linked. TCR gene rearrangements were two to three times more frequent in CD34- and My-pro T-ALL. However, both CD34+ and My+ pro T-ALL showed an incidence of mediastinal masses and polar acid phosphatase positivity similar to this observed in CD34- and My- cases. This supports the assumption that both types of ALL indeed are engaged in the T-lineage, and confirms intracytoplasmic cCD3 as the earliest marker for this lineage. Moreover, CD34 appears to persist up to an early stage of T-cell maturation, where the cells retain myeloid potentiality. Loss of CD34 correlates with TCR-beta gene rearrangement and definitive commitment to the T lineage. Event-free survival analysis suggested a poorer outcome for pro T-ALL in adult patients.

Adolescent↗
PubMed1992

[Expression of HLA-DP antigens on normal and leukemic blood cells].

HLA-DP allodeterminant elicit weak cellular and humoral immune responses. This study was undertaken to find out if the low immunogenicity of HLA-DP could be accounted for by a low level of expression on peripheral blood mononuclear cells. Double staining experiments and flow cytometry were performed in 28 healthy individuals, HLA-DP was found to be as expressed as DR and DQ on B lymphocytes. Furthermore, a DP+/DR- lymphocyte sub-population was identified and characterized as freshly activated T lymphocytes.

Adult↗
PubMed1992

Surface markers in adult acute myeloblastic leukemia: correlation of CD19+, CD34+ and CD14+/DR--phenotypes with shorter survival. Groupe d'Etude Immunologique des Leucémies (GEIL).

The immunophenotype of blast cells was investigated in a multicentric study of 154 adult acute myeloblastic leukemias (AMLs). A panel of 27 monoclonal antibodies (MoAbs) was tested in indirect immunofluorescence. Expression of CD14 (UCHM1), CD19 (SB4), CD36 (OKM5), and HLA-DR were associated with higher mean leucocyte counts. CD14 expression correlated with low hemoglobin level and the absence of CD33 (MY9) with low platelet counts. Extramedullary disease was associated with CD16 (Leu11b) and HLA-DR antigen positivity. The study of relationships between surface markers and FAB criteria confirmed the predominant expression of CD14 in the M5 sub-group (p less than 0.000001) and the association of CD19 and CD36 with monocytic M4/M5 subgroups (respectively p less than 0.00002 and p less than 0.000001). All patients received an induction therapy including an anthracycline and cytarabine. The median follow-up was 13 months. The achievement of complete remission (CR) was inversely correlated with CD34 (B13C5) and CD19 expression: CR was obtained in 31 of 59 (53%) CD34-positive AML versus 64 of 75 (85%) CD34-negative cases (p less than 0.0001) and 11 of 24 (46%) CD19-positive versus 95 of 122 (78%) CD19-negative cases (p less than 0.01). In univariate analysis, a longer survival was associated with CD33 expression and the combined phenotypes CD36+/CD19- and CD16+/CD14-. Conversely, the CD18(IOT18)+/CDw65(VIM2)- phenotype was related to shorter survival. The expression of CD19, of CD34, and of the combined phenotype CD14+/DR--correlated with shorter survival as demonstrated both in univariate and multivariate analysis (p less than 0.03 in each case in multivariate analysis).

Antigens, CD↗
PubMed1992

Hairy cell leukemia and factor VIII inhibitor: a case report.

Acquired factor VIII inhibitors are usually described in hemophilia A, although some cases have been documented in chronic inflammatory diseases and malignant tumors. We report here the first case of a factor VIII inhibitor appearing in the course of hairy cell leukemia. Interferon therapy over a 5 month period led to complete remission of leukemia with parallel disappearance of the acquired factor VIII inhibitor.

Factor VIII↗
PubMed1989

Class II alloantigen expression on leukemic cells.

Class II antigen expression on leukemic cells has been mainly studied using monoclonal antibodies (Mabs). On the other hand, class II polymorphism has been mainly studied using alloantisera. The present study shows that the reactivity of leukemic cells from different lineages with class II Mabs was not always the same as that obtained with alloantisera and that the reactivity varied depending on the leukemic cell-type studied.

Antibodies, Monoclonal↗
PubMed1989

Elevated serum levels of soluble interleukin-2 receptors in HIV infection: no correlation with activated T cells.

Serum levels of soluble interleukin-2 receptors (sIL-2R) were measured in 105 HIV-seropositive individuals simultaneously with T cell subsets and activated T cells (CD3+ and HLA-DR+). Significantly elevated levels of serum sIL-2R were found (564 +/- 259 U/ml versus 258 +/- 87 U/ml in 70 controls, p less than 0.001), as well as increased numbers of activated T cells (mean numbers, 579/microliters in the patients versus 113/microliters in 26 controls, p less than 0.0001). Correlation analysis did not disclose any significant association between elevated sIL-2R and increased activated T cells, nor with decreased CD4+ lymphocytes. These data suggest that sIL-2R in HIV infection do not emanate from activated T cells and are not linked to CD4+ cell loss.

Adolescent↗
PubMed1988

[Role of allogeneic transplantation of bone marrow in juvenile chronic myelomonocytic leukemia].

Two boys with clinical and haematological evidence of juvenile chronic myelomonocytic leukaemia had no chromosomal anomaly. In addition, one presented with an unbalanced Epstein-Barr virus serology, and the other with xantholeukaemia. Allogenic bone marrow transplantation was performed in the first boy after an 18-month period during which treatment with 6-mercaptopurine, intensive chemotherapy and splenectomy had failed. Conditioning included cyclophosphamide, high-dose cytarabine and whole-body irradiation. There was no complication, and 16 months after transplantation the patient was in complete remission. The second boy received a bone marrow transplant on the 6th month of the disease, after failure of 6-mercaptopurine. Conditioning included etoposide, busulfan and cyclophosphamide. On the 35th post-transplantation day the child had severe pancytopenia and his spleen remained enlarged. A second transplantation was performed after treatment with melphalan and whole-body irradiation. Twelve months later, the patient was in complete remission. The indications and modalities of allogenic bone marrow transplantation in juvenile chronic myelomonocytic leukaemia and the value of pre-transplantation splenectomy are discussed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Randomised, double-blind, placebo-controlled trial of ditiocarb sodium ('Imuthiol') in human immunodeficiency virus infection.

83 patients with human immunodeficiency virus (HIV) infection (CDC groups II, III, or IV-A) were randomised in a crossover trial of sodium-diethyldithiocarbamate (ditiocarb sodium, 'Imuthiol') (10 mg/kg body weight given orally once a week) against placebo. Each arm of the trial lasted 16 weeks. The disease did not progress to CDC-defined acquired immunodeficiency syndrome in the ditiocarb group but did so in 4 patients in the placebo group (3 between week 0 and 16, 1 between week 17 and 32). Ditiocarb was also associated to a significantly greater extent than placebo with relief of constitutional symptoms, improvement in clinical status (including shrinkage of enlarged spleen and lymph nodes), and improvement in immune function (as measured by CD4+ cell count and skin test reactivity). When placebo was replaced by ditiocarb, similar improvements were observed, whereas symptoms slowly reappeared and CD4+ cell levels progressively declined when ditiocarb treatment was replaced by placebo.

Acquired Immunodeficiency Syndrome↗