PubMed HealthSearch

Biomedical subjects

P Resnitzky

Publications and source records attributed to P Resnitzky.

At least 19 recordsLinked to original sources

Absence of negative growth regulation in three new murine radiation-induced myeloid leukemia cell lines with deletion of chromosome 2.

Murine radiation-induced acute myeloid leukemia (RI-AML) may be considered as the experimental counterpart of human secondary leukemia. Three new myelomonocytic cell lines derived from RI-AML and carrying a partially deleted chromosome 2 are described. The RI-AML cells responded with increased proliferation after being incubated with the hemopoietic growth factors rG-CSF, rGM-CSF and IL-3. Increased proliferation of the same extent without any effect in differentiation, was also demonstrated in the RI-AML cells after incubation with IL-6 and with mouse lung conditioned medium (CM) and Krebs ascites tumor cells CM which induce differentiation in normal and most leukemic myeloid cells. Down-regulation of the c-myc gene and induction of (2'-5') oligo-adenylate synthetase (reflecting autocrine interferon secretion), two essential mechanisms operating during arrest of growth and concomitant differentiation, were demonstrated to be absent in RI-AML cells. In contrast, the M1 cells responded to the above differentiating factors with growth arrest and differentiation and with appropriate c-myc down-regulation and synthetase induction. The genetic basis for the distinct RI-AML cells' behavior may be connected with the loss or structural and/or functional abnormalities of DNA sequences located in the deleted part of chromosome 2 or in the respective allele. The presently described new RI-AML cell lines may be used for studies concerning myeloid leukemogenesis in general and secondary leukemia in particular.

2',5'-Oligoadenylate Synthetase

Multiphase process involved in radiation induced murine AML.

Exposure of 3 month old SJL/J mice to a single dose of 300 r yielded 15-30% acute myelomonocytic leukemia (AML) development at a mean latency of 1 year. Additional treatment with dexamethasone shortly after irradiation increased leukemia incidence to 50%. All tumors were characterized by a partial deletion of one allele of chromosome 2 and the same deletion was detected in bone marrow and spleen cells of most irradiated mice, irrespective of the development of the disease. The presence of potential leukemic cells (PLC) in mice 4 months after the leukemogenic treatment was confirmed by transplantation studies. In these experiments PLC transition into overt AML seemed to be dependent on their transfer into irradiated recipients. Thus, exposure to 300 r results in the initiation of potential leukemic cells. Experiments were conducted in order to explore the possible role of radiation, cytokines and different hemopoietic growth factors on PLC promotion to overt leukemia. Exposure to 300 r, beside PLC initiation, was found to trigger the production of IL-6 and CSF-1; the additional administration of dexamethasone further increased CSF-1 levels. In vivo administration of CSF-1 into mice carrying radiation-induced PLC was most effective in PLC promotion to overt AML development.

Animals

Initiation and promotion in radiation-induced myeloid leukemia.

Acute myelomonocytic leukemia develops in 10-30% of irradiated (300 rad) SJL/J mice, after a lag period of around one year. Additional treatment with dexamethasone shortly after irradiation increased leukemia incidence up to 50%. Experiments were conducted in order to demonstrate the existence of preleukemic cells in irradiated mice and to explore the possible role of dexamethasone, cyclophosphamide, and different hemopoietic growth factors on their promotion to overt leukemia. Transplantation of bone marrow cells from mice exposed to 300 rad plus dexamethasone into appropriate recipients, performed 4-5 months after leukemogenic treatment, resulted in acute myeloid leukemia (AML) development of donor origin in 70% of the recipients. Transfer of fractionated preleukemic bone marrow showed that the highest AML incidence developed in the recipients of fractions enriched in early hemopoietic precursors. The promoting effect of dexamethasone on preleukemic cells was confirmed by demonstrating its similar coleukemogenic effect whether administered within several hours or 130 days after radiation. Treatment with cyclophosphamide shortly after radiation could not replace the dexamethasone effect but was found to be complementary to the coleukemogenic effect of dexamethasone. Early administration of hemopoietic growth factors (starting 14 days after radiation and dexamethasone) showed that colony-stimulating factor (CSF) 1 increased the AML incidence (75%) and reduced its latency. Treatment with recombinant granulocyte-CSF (rG-CSF) had a reduced effect and recombinant granulocyte-macrophage CSF (rGM-CSF) had no promoting effect. However, administration of different factors several months after the leukemogenic treatment revealed that rGM-CSF increased AML incidence (75%) and shortened its latency, whereas rG-CSF and CSF-1 had no effect. In contrast, the late administration of recombinant interleukin 6 reduced AML incidence significantly (23%). The present results indicate that murine radiation induced AML is a multiphase process involving radiation induced preleukemia that can be promoted by different treatments.

Animals

Late appearance of thrombotic thrombocytopenic purpura after autoimmune hemolytic anemia and in the course of chronic autoimmune thrombocytopenic purpura: two case reports.

The association between thrombotic thrombocytopenic purpura (TTP) and autoimmune hematological conditions is reported in 2 patients. In a 35-year-old man, acute autoimmune hemolytic anemia (AIHA) was diagnosed in 1960; until 1965 he was free of disease, when he abruptly developed TTP and failed to respond to blood transfusions and corticosteroids. In a 14-year-old girl, autoimmune thrombocytopenic purpura (AITP) was diagnosed in 1981 and treated with corticosteroids and splenectomy. Four years later the patient was admitted with acute catastrophic signs and symptoms of TTP and failed to respond to plasmapheresis and plasma transfusions. The present case reports of associations between AIHA and AITP with TTP support the connection of the latter with abnormalities of the immune system.

Adolescent

Effect of Graves' disease on idiopathic thrombocytopenic purpura.

The association between hyperthyroidism and thrombocytopenia is a known although infrequent clinical condition. Distinct mechanisms are probably active in each particular case, but the thyrotoxic state has been implicated as having a key effect on the fall in the number of platelets. We describe a patient with coexisting Graves' disease and idiopathic thrombocytopenic purpura who showed special refractoriness to treatment of the bleeding condition in the thyrotoxic state, but who promptly responded to treatment when the thrombocytopenia relapsed 2 1/2 years later, while he was euthyroid. Thus, in this case, a clear exacerbating effect of the thyrotoxic state on the thrombocytopenia was observed. We suggest evaluation of the thyroid condition in patients suffering from refractory thrombocytopenia.

Adult

Surface charge characteristics of peripheral blood lymphocytes in chronic lymphatic leukemia and malignant lymphoma.

Peripheral blood lymphocytes from patients with chronic lymphatic leukemia (CLL) and malignant lymphoma (ML) were tested for their surface negative charge characteristics and compared with lymphocytes from normal subjects by use of measurements of lymphocyte agglutination with a positively charged poly-L-lysine (PLL) molecule and by use of electron microscopic observation of lymphocytes labeled with cationized ferritin (CF). Unfixed lymphocytes from CLL and ML patients exhibited clustering and patching of CF particles, whereas normal lymphocytes had a uniform, continuous CF-labeling pattern. Lymphocytes from CLL patients had significantly higher agglutination with PLL than did normal lymphocytes.

Adult

Neutrophilic turnover rate in human age groups evaluated by serum lysozyme activity.

Serum lysozyme activity was determined in 135 healthy people classified into five different age groups ranging from 20 to 90 years. A turbidometric method with egg-white lysozyme as standard enzyme using the Fragiligraphy for automatic recording of the serum lysozyme was used. The results show a progressive increase in serum lysozyme activity with age. In the oldest age group of 60-90 years, the increase in serum lysozyme was more than that expected for the diminished glomerular filtration rate in old age. Since the serum level of lysozyme can reflect the rate of neutrophilic turnover, it can be assumed that this rate increases above the age of 60.

Adult

Association between thyrotoxicosis and thrombocytopenia. A case report and review of the literature.

In a young woman who presented with hyperthyroidism and autoimmune thrombocytopenic purpura, the platelet count returned to normal following successful treatment of the hyperthyroidism. Thromboagglutinins were present, the titer declining as the patient became euthyroid. A survey of the literature revealed 48 reports of hyperthyroidism and thrombocytopenia, these disorders coexisting in 37 patients and there being no apparent cause for the lowered platelet counts in 28 of them. The clinical features and response to treatment in the latter group and in our patient are reviewed, comprising a series of 29. Of 22 patients whose hyperthyroidism was adequately treated, platelet counts returned to normal in 18 (82%). In three patients the purpura remitted despite persistent thrombocytopenia. It is estimated that in 7% of patients with autoimmune thrombocytopenic purpura, thrombocytopenia responds to treatment of an underlying thyrotoxicosis and in many of these patients the thrombocytopenia will prove resistant to other forms of therapy.

Adult

Osmotic fragility of peripheral blood lymphocytes in chronic lymphatic leukemia and malignant lymphoma.

The osmotic fragility (OF) of peripheral blood lymphocytes from patients with chronic lymphatic leukemia (CLL) and non-Hodgkin malignant lymphoma (ML) was investigated employing an automatic recording method and compared with that of lymphocytes from healthy subjects and from patients suffering from various non-neoplastic diseases. The curves from CLL and ML showed a pattern of increased lymphocyte OF compared with those of the two control groups, and the difference was statistically significant ( less than 0.001). In CLL the increase in OF was more pronounced than in ML, and the shape of the curve was different from that in the other groups. The employment of peripheral blood lymphocyte OF as an additional diagnostic parameter in the diagnosis of CLL and ML is suggested.

Adult