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Biomedical subjects

A Falkenrodt

Publications and source records attributed to A Falkenrodt.

At least 37 records · Page 2Linked to original sources

[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↗

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↗

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↗

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↗

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↗

[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↗

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↗

HLA class I antigens on normal and leukemic cells (quantitative analysis).

A monomorphic anti-Class I monoclonal antibody, ST01, found in our laboratory, was used to quantify Class I antigens on normal and leukemic cells, using a "CELISA" technique. Saturation graphs were used to compare the quantity of Class I antigens on normal PBL (25 cases) with that on the following types of leukemic cells: a) common acute lymphoblastic leukemias (cALL) (11 cases), b) mature B lymphocytic proliferations (16 cases), c) T hemopathies (9 cases), d) non-lymphoid leukemias (9 cases). In most cases the quantity of HLA Class I antigens was greatly reduced. No correlation was found between the quantitative expression of Class I antigens and the stage of maturation in each cell type, nor was any correlation found between the quantitative expression of Class I antigens on the leukemic cells and the proliferation of leukemic cells in the peripheral blood.

B-Lymphocytes↗

Decreased membrane "fluidity" of T lymphocytes from untreated patients with Hodgkin's disease.

Plasma membrane "fluidity" of peripheral blood T lymphocytes from untreated patients with Hodgkin's disease (HD) and healthy controls was studied using the fluorescent probes 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1-(4(trimethylamino)phenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH). In 13 consecutive patients a significant increase of T lymphocyte plasma membrane microviscosity was observed with both DPH and TMA-DPH. These alterations seemed unrelated to the cholesterol (Chol) and phospholipid (PL) content of HD T lymphocytes since the Chol/PL ratio was comparable in both HD and control cells. Since prostaglandin E2 (PGE2) from monocytic origin has been claimed to be responsible for the impairment of cell-mediated immunity (CMI) associated with HD, we studied the effect of exogeneously added PGE2 (0.1 microM) on control subjects T lymphocyte membrane "fluidity". Using the fluorescent probe DPH and the spin labelled fatty acid probe 16 NMS for electron paramagnetic resonance study, we observed a PGE2-induced fluidization of control T lymphocyte membranes which is specifically located in the inner part of the plasma membrane, whereas the plasma membrane surface seemed unaffected by PGE2 as judged by the TMA-DPH probe. Thus, PGE2 does not appear to be responsible for the alterations of T lymphocyte membranes observed in HD. Intrinsic alterations and/or other mediators might be involved.

Adult↗

New human MHC class I antigens segregating with HLA-A antigens detected on some lymphocyte subpopulations.

Recent genetic studies of the murine chromosome 17 have demonstrated that many genes encode class I antigens, most of which are still not detected serologically; most of these genes belong to the Tla region. Five human alloantisera were selected from 383 female sera and were further studied using a panel of peripheral blood lymphocytes (PBL), B lymphocytes (BL), and PHA activated lymphocytes (PHA-L) from the same blood donors. After intensive platelet absorption, the five sera still reacted positively by a complement-dependent cytotoxicity technique with PHA-L, but negatively with PBL and BL. The antigens detected by these antibodies segregated with an HLA-A allele and were assumed to belong to the class I antigen series as they could be blocked by a turkey anti-beta 2 microglobulin serum. They were found on some lymphocyte populations: PHA-L, common acute lymphoblastic leukemia (cALL) cells, and (preliminary results) a small subpopulation of PBL cells (mostly NK cells), but were not found on chronic lymphocytic leukemia (CLL) cells, T and early T acute lymphoblastic as well as myeloblastic leukemia cells. Kinetic studies showed that several hours of culture with PHA were necessary for the antigen to be expressed. These results show that the antigens described do not belong to the classic HLA antigen series but could be considered to belong to the human Qa-like antigens or to be the human counterpart to the second murine H-2K locus antigens.

Antigen-Antibody Complex↗

[Expression of class I and class II markers on populations of leukemic cells].

The study of class I and class II antigen expression on leukemic cells brought the following conclusions: most of the leukemic cells show a slower number of class I antigenic sites than normal peripheral blood lymphocytes (PBL) but, in most cases, this does not hinder HLA typing; contrarily to normal PBL, leukemic cells seem to carry "non HLA" antigens (and/or non classical HLA antigens) which are probably responsible of the false positive reactions frequently observed at the time of HLA typing; most of the leukemic cell types express DR antigens (except those belonging to the T lineage) but DQ antigen expression (and in some cases MT antigen expression) varies depending on the cell type studied: well defined on mature B hemopathies, DQ expression is often lower than DR expression on acute leukemic cell types.

HLA Antigens↗

Natural HLA antibodies.

"Natural antibodies" directed against antigens of the Major Histocompatibility Complex have been observed in aged mice but very seldom in humans. It is likely that HLA natural antibodies are more common than previously supposed: our results suggest they may be found in 1% of normal blood donors. Most of these antibodies seem to be weak and can only be detected when B lymphocytes (BL) are used as target cells in the lymphocytotoxicity technique or when indirect immunofluorescence is used with peripheral blood lymphocytes (PBL). The behavior of these natural IgM antibodies was compared to that of weak immune IgG HLA antibodies detected in the same way. Absorption tests showed that "natural antibodies" were very specifically absorbed, whereas "immune antibodies" could also be absorbed by cells not carrying the specific antigen. Furthermore, about half of the "natural antibodies" detected to date carried the HLA-B8 specificity. Various hypotheses have been put forward to attempt to explain the appearance of these antibodies.

Adult↗

Isoprinosine and Imuthiol, two potentially active compounds in patients with AIDS-related complex symptoms.

Isoprinosine and Imuthiol are immunomodulators with a unique effect on T-cells. The possibility of using them in treating patients with acquired immunodeficiency syndrome related complex (ARC) was initially examined regarding their in vitro effects on peripheral blood mononuclear cells. In six ARC patients Isoprinosine (100 micrograms/ml) and Imuthiol (10 pg/ml) induced in vitro an early chromatin activation as measured by nuclear refringency test and potentiated phytohemagglutinin (5 micrograms/ml) in the same 20-min assay in the absence of fetal calf serum. In all patients an early phytohemagglutinin induced chromatin dispersion was observed with a dose related response before interleukin 2 production can occur. Isoprinosine and Imuthiol increased significantly both the percentage and the absolute number of T4+ cells when peripheral blood mononuclear cells were incubated for 4 days in RPMI supplemented with 10% fetal calf serum. No changes in T8+ cells were noted. Three homosexual ARC patients were then treated p.o. with Imuthiol (5-10 mg/kg/week) for 4 to 6 months. Without any deleterious effect a clinical improvement (in terms of adenopathy and opportunistic infection regression) and restoration of the response to recall antigens were observed in all three patients. One patient with less than 500 T4+ lymphocytes/mm3 exhibited a complete restoration of OKT profiles. In such patients clinical and immunological effects of Isoprinosine have already been reported by others. Altogether these preliminary results indicate that more data should be obtained on the effects of these two agents in ARC patients.

Acquired Immunodeficiency Syndrome↗

Membrane markers, karyotypic abnormalities, ultrastructure and functional properties of lymphocytes in a case of 'D-cell' chronic lymphatic leukemia.

D cells are lymphocytes bearing both receptors for the third complement component and the ability to form spontaneous rosettes with SRBC. We report the case of a patient with a D-cell chronic lymphatic leukemia who presented a long evolution without treatment and whose leukemic cell characteristics have been extensively studied. Cytogenetic analysis showed numerous karyotypic abnormalities among leukemic cells; all metaphases were hypodiploid and arranged in four different clones; seven marker chromosomes were present. The cells were found to bear human T-cell specific antigen, the T helper/inducer phenotype, HLA-A and HLA-B determinants, but no HLA-DR antigens. They displayed a high proliferative response to PHA and Con A, no response to PWM stimulation, and possibly the capacity of allogeneic stimulation in the mixed lymphocyte culture system. Assays for cell-mediated cytotoxicity in the CML system, and for K and NK activities were negative.

Antigens, Surface↗