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Biomedical subjects

D Douer

Publications and source records attributed to D Douer.

At least 55 records · Page 3Linked to original sources

Carbon dioxide laser effect on platelet function and surface ultrastructure in vitro.

Platelet aggregation may be an important factor in the feasibility of transcatheter laser angioplasty. The in vitro effects of increasing doses of CO2 laser irradiation on platelet number, function, and surface ultrastructure were examined. Results indicated a progressive dose-response reduction of both platelet number and function following laser irradiation. By scanning electron microscopy the irradiated platelets showed dose-related changes in pseudopods as well as progressive damage of the cell membrane.

Adult↗

Late immune and haemopoietic functions in plasmacytoma-bearing mice cured by melphalan.

Alkylating agents can cause latent and permanent damage to the bone marrow. We compared the long term effects of melphalan on a number of immune and haemopoietic functions of plasmacytoma bearing BALB/c mice with that of normal mice treated with a similar dose of melphalan. The drug administered orally at a dose of 250 micrograms and 400 micrograms on day 14 and 24 following i.m. inoculation of MOPC-315 plasmacytoma cells resulted in cure of the mice. Their spleen cells showed a permanent impairment of MLR activity, T-cell number and IL-2 production as well as a mild suppression of NK activity for one year after cessation of melphalan therapy. The number of B cells was elevated. In contrast, plasmacytoma-free mice treated with melphalan retained long term normal immune functions, although shortly after melphalan therapy a temporary suppression was noted. On the other hand, melphalan was responsible for bone marrow myeloid stem cell damage since the number of myeloid progenitor cell (CFU-GM) colonies was reduced in both melphalan-treated groups compared to untreated normal controls. Plasmacytoma bearing mice had a shorter survival. These results demonstrate that some late sequelae of alkylating agents are not due to the drug alone; shorter survival and T-cell deficiency are related to the previous presence of the tumour.

Animals↗

Methimazole-induced agranulocytosis: growth inhibition of myeloid progenitor cells by the patient's serum.

The mechanism for agranulocytosis induced by antithyroid drugs is not established. The few available studies have proposed an immune-mediated process against mature granulocytes. We investigated the effect of methimazole and propylthiouracil and serum from a patient with methimazole-induced agranulocytosis on marrow myeloid colony growth. In the presence of normal serum or patient's recovery serum, antithyroid drugs had no effect on the growth of CFU-GM colonies from normal or patient's marrow. However, the patient's serum obtained during agranulocytosis inhibited the in vitro myeloid colony growth from both autologous and allogeneic bone marrow. These results are compatible with an immune-mediated mechanism for methimazole-induced agranulocytosis rather than a direct toxic effect of the drug on abnormally sensitive cells.

Adult↗

T-cell acute lymphoblastic leukemia with severe leukopenia: evidence for suppression of myeloid progenitor cells by leukemic blasts.

A patient with T-cell acute lymphoblastic leukemia presented with leukopenia due to neutropenia, no circulating blasts and normal hemoglobin level. Marrow leukemic T lymphoblasts inhibited in vitro normal CFU-GM colony growth and released an activity that stimulated normal BFU-E growth. This patient demonstrates that immature T cells may modify hematopoietic stem cell growth both in vitro and in vivo.

Adult↗

HTLV-I-associated T-cell leukemia/lymphoma in Israel.

Human T-cell lymphotrophic virus Type I (HTLV-I)-associated adult T-cell leukemia/lymphoma (ATL) is a relatively new clinical entity. The disease is endemic in southwestern Japan, the Caribbean basin, the southeastern United States and Africa. We report the identification of this disease in Israel and review previous cases of HTLV-I infection and ATL in this region. The disease was initially indolent and later clinically aggressive, characterized by hypercalcemia, osteolytic bone lesions, leukemic skin and organ infiltration and opportunistic infection.

Deltaretrovirus Infections↗

Gastrointestinal phycomycosis in acute nonlymphatic leukemia.

A 37-year-old patient with acute nonlymphatic leukemia developed gastrointestinal phycomycosis during failure in bone marrow production. The clinical presentation was of acute typhlitis. Laparotomy revealed a necrotic mass in the region of the iliocecal valve, and on histologic examination hyphae of phycomycetes with invasion of the blood vessels were seen. The patient died as a result of widespread infection.

Acute Disease↗

Human Exserohilum and Bipolaris infections: report of Exserohilum nasal infection in a neutropenic patient with acute leukemia and review of the literature.

A neutropenic patient with acute myeloid leukemia developed nasal and perinasal infection caused by the fungus Exserohilum rostratum. Early amphotericin B treatment along with marrow recovery resulted in resolution of the infection. A review of other previously reported cases of Exserohilum and Bipolaris infections show a favourable outcome in most patients who receive systemic antifungal treatment with amphotericin B.

Agranulocytosis↗

Myelodysplastic syndrome: a review of 35 patients.

Thirty-five patients with myelodysplastic syndromes were retrospectively classified according to the FAB classification (French-American-British Cooperative Study Group). Their prognosis was found to be dependent mainly on the presence of blasts in bone marrow examination. Those with an excess of blasts in their bone marrow had a median survival of 30 months in contrast to 66 months in those without blasts. These results were compared with those of seven recent reported series.

Adult↗

Monocyte produced burst-promoting activity after stimulation with lymphokine.

Normal monocytes were stimulated by lymphokine(s) from a homogenous population of malignant T cells of the helper phenotype (OKT 3+/4+/6-/8-/11+). The resultant monocyte-conditioned medium after stimulation with T cell-conditioned medium (M-CM+) was assayed for burst-promoting activity. The number of burst-forming units-erythriod (BFU-E) in methylcellulose cultures of normal human nonadherent peripheral blood cells increased by nearly threefold in the presence of 5% M-CM+. This activity was lost after the conditioned medium was boiled for 20 min. The addition of 5% conditioned medium (CM) from unstimulated monocytes did not significantly increase BFU-E proliferation. We conclude that lymphokine(s) from malignant T cells of the helper phenotype stimulate normal monocytes to produce a heat-sensitive monokine that increases BFU-E proliferation.

Colony-Forming Units Assay↗

Normal natural killer cell activity in Hodgkin's disease patients in remission.

Patients with untreated active Hodgkin's disease (HD) have a defect in cell-mediated immunity. After therapy many HD patients still have long lasting abnormalities in T cell number and function. We examined whether NK activity is also permanently impaired in HD patients in remission. The mean NK activity of peripheral blood lymphocytes from 42 patients who were disease-free for 6-150 months was not different from that of healthy controls. Augmentation of NK activity after treatment of the cells by interferon in vitro was equal for patients and controls. Normal NK activity in HD in remission was independent of disease stage, age, remission duration and mode of therapy. Measuring PHA-induced lymphocyte proliferation and NK activity simultaneously demonstrates that patients with impaired cell-mediated immunity do not have concomitant reduction of NK activity. We conclude that NK activity in HD in remission is independent of decreased T cell mediated immunity. In addition, NK is resistant to long term suppression by the chemotherapy and radiation protocols that are used in HD.

Adult↗

Demonstration of clonable alloreactive host T cells in a primate model for bone marrow transplantation.

The phenomenon of marrow rejection following supralethal radiochemotherapy was explained in the past mainly by non-T-cell mechanisms known to be resistant to high-dose irradiation. In the present study a low but significant number of radiochemoresistant-clonable T cells was found in the peripheral blood and spleen of Rhesus monkeys following the cytoreductive protocol used for treatment of leukemia patients prior to bone marrow transplantation. More than 95% of the clonable cells are concentrated in the spleen 5 days after transplant. The cells possess immune memory as demonstrated by the generation of alloreactive-specific cytotoxicity. The present findings suggest that host-versus-graft activity may be mediated by alloreactive T cells. It is hoped that elimination of such cells prior to bone marrow transplantation will increase the engraftment rate of HLA-nonidentical marrow in leukemia patients.

Animals↗

Human spleen cell generation of factors stimulating human pluripotent stem cell, erythroid, and myeloid progenitor cell growth.

Mitogen-stimulated murine spleen cells produce humoral substances capable of supporting murine hematopoiesis and pluripotent stem cell proliferation in vitro. Thus, we evaluated conditioned media generated by human spleen cells (SCM) in the presence or absence of mitogens for factors stimulatory for human pluripotent (CFU-GEMM), erythroid (BFU-E), and myeloid (CFU-GM) precursors. Two and one half percent to 10% SCM stimulated proliferation of all three types of precursor cells from nonadherent buoyant human marrow target cells. Mitogen-stimulated SCM augmented CFU-GM (175% to 225%), whereas CFU-GEMM and BFU-E growth was essentially unchanged. Cell separation procedures used to determine which cells provided these microenvironmental stimuli indicated that nonadherent mononuclear spleen cells provided the bulk of the CSF-GM, whereas adherent cells (95% nonspecific esterase + monocyte-macrophages) and nonadherent cells provided similar proportions of CSF-mix and erythroid burst-promoting activity (BPA). The nonadherent cells generating high levels of CSF-mix, BPA, and CSF-GM were predominantly Leu-1-negative, ie, non-T, cells. In the presence or absence of mitogens, SCM was a more potent source (1.3- to 3.8-fold) than peripheral leukocyte CM of the growth factors for the three progenitor cell types. Specific in situ cytochemical stains for analyzing morphology of myeloid colonies demonstrated that SCM stimulated the proliferation of the same types and proportions of colonies as human placental CM, suggesting that these CMs may contain similar CSF-GMs. These data show the contribution of spleen cell subsets to the generation of hematopoietic growth factors and the responsiveness of these cells to various mitogenic stimuli.

Bone Marrow Cells↗

Production of burst-promoting activity by monoclonal antibody defined malignant T lymphocytes from patients with lymphocytic leukemia and lymphoma.

We tested conditioned media from 12 patients with T lymphocyte neoplasms and four T cell lines for their ability to stimulate the in vitro growth of erythroid-burst-forming units (BFU-E) from bone marrow mononuclear cells in a methylcellulose culture system. Nine patients suffered from acute lymphocytic leukemia, two from chronic lymphocytic leukemia, and one from non-Hodgkin's lymphoma. The T lymphocytes were characterized by a series of monoclonal antibodies and their stage of development was correlated with their ability to produce burst-promoting activity (BPA). Conditioned media from cells classified as prothymocytes (three cases), common thymocytes (one case), mature thymocytes (three cases), and mature lymphocytes of the helper subtype (two cases) increased BFU-E proliferation four- to 19-fold over control values using normal bone marrow as target cells. Conditioned media from OKT8+ malignant T lymphocytes (three cases) did not enhance BFU-E proliferation. Conditioned media from cells classified as immature T cells stimulated CFU-GM proliferation in only one of seven cases even though they secreted BPA. Conditioned media from three of the four cell lines stimulated by phytohemagglutinin, enhanced BFU-E growth. Our results indicate that malignant cells that have characteristics of immature T cells are able to produce BPA. Studies using techniques to isolate homogeneous populations of normal T cell subsets are required to determine whether normal immature T lymphocytes have the same capability.

Antibodies, Monoclonal↗

Production of colony-stimulating activity (CSA) by T-chronic lymphocytic leukemia cells.

T-lymphocytes are probably involved in regulating myelopoiesis. We show that homogeneous populations of leukemic T-lymphocytes freshly obtained from two patients with T cell chronic lymphocytic leukemia produce colony-stimulating activity. The cells from both patients showed the antigenic and biochemical phenotype of the mature T-lymphocyte of the helper subset. This adds further support to the view that helper T-lymphocytes may regulate hematopoiesis in addition to their role in the immune function.

Adenosine Deaminase↗

Amodiaquine-induced agranulocytosis: drug inhibition of myeloid colonies in the presence of patient's serum.

We report a patient who developed agranulocytosis following exposure to three drugs: amodiaquine, pyrimethamine and dipyrone. The combination of amodiaquine with the patient's serum, obtained during the agranulocytosis, inhibited in vitro granulocyte-monocyte colony-forming unit (CFU-GM) growth of autologous and allogeneic marrow. These results support the view that amodiaquine-induced agranulocytosis is immune in nature. This in vitro approach may be used to study the mechanism of drug-induced agranulocytosis, especially when patients are exposed to multiple drugs.

Agranulocytosis↗