Search PubMed⌕ Search

Biomedical subjects

P Resnitzky

Publications and source records attributed to P Resnitzky.

At least 37 records · Page 2Linked to original sources

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↗

Age related changes in hemopoietic capacity of bone marrow cells.

The effect of aging on the hemopoietic capacity of bone marrow (BM) cells was investigated. No difference was found in the incidence of colony forming units-spleen (CFU-S) and granulocyte-macrophage colony forming cells (GM-CFC) present in the BM of young (2-4 months) or old (24-30 months) mice. However, increased proliferation (x3) of the old BM cells was observed when cultured in the presence of L-cell conditioned medium. The cells were also cultivated over an adherent layer of a BM stroma cell line (14F1.1, endothelial-adipocytes) and the non-adherent cells removed and tested weekly. Cells originating from the old BM proliferated to a greater extent and produced more GM-CFC than those from the young. Differentiation into T-cells after colonizing fetal thymus explants was also measured and found to be reduced in both groups, though to a greater extent in the old. Thus, under the present experimental conditions, myeloid progenitors in the old BM manifest a more pronounced self renewal and differentiation capacity than the young while for the T-cell progenitors the situation is reversed.

Aging↗

Circulating mononuclear cells from pure red cell aplasia of chronic lymphocytic leukemia suppress in vitro erythropoiesis.

In vitro studies were performed in a patient with B-cell chronic lymphocytic leukemia who developed pure red cell aplasia (CLL-PRCA). The patient's irradiated circulating mononuclear blood cells and supernatant markedly inhibited normal marrow erythroid (but not granulocyte-monocyte) progenitor colony proliferation. In contrast, irradiated peripheral blood mononuclear cells and supernatant obtained from a B-CLL patient (Rai stage III) and from a hematologically normal donor, did not affect hematopoietic progenitor colony growth. These findings suggest that the anemia of CLL-PRCA evolves different mechanisms of those causing anemia in CLL, and is mediated through cellular and secretory mechanisms.

Aged↗

Serum and effluent lysozyme (muramidase) activity in CAPD patients.

The elevated serum lysozyme activity in 13 chronic renal failure patients (n = 26) dropped significantly during their first three months of CAPD and subsequently returned to initial levels. When compared with peritoneal mass transfer of lysozyme and serum creatinine levels, a distinct correlation was observed between these and the fluctuations in serum lysozyme activity recorded up to three years of CAPD (r = 0.319, P less than 0.05 and r = 0.425, P less than 0.025, respectively). A notable drop in the mass transfer of this low molecular weight protein took place after the first hour of dialysis. We concluded that long-term CAPD does not affect serum lysozyme activity and that passive loss across the peritoneal membrane could account for the lysozyme found in the effluent fluid.

Adolescent↗

Variations in surface charge distribution of leukemic and non-leukemic transformed cells.

The surface negative charge distribution of fresh leukemic cells from patients with acute leukemia was examined with cationized ferritin (CF), an electron dense label of anionic sites and compared with leukemic cells from phase-cycle fractionated populations of a human leukemic cell line K-562. Normal-untreated and phytohemagglutinin (PHA)-transformed lymphocytes were also tested. A CF-induced redistribution of anionic sites into clusters and patches within a wide range of variations in density was observed electron microscopically both in fresh acute leukemic cells and in unseparated cells of the K-562 line. Cells of the G0/G1 fraction from a phase-cycle separated K-562 population exhibit a higher density of CF label per unit length of membrane as compared with the G2 + M cell fraction. PHA-benign transformed normal lymphocytes exhibit an even and continuous CF labeling, similar to that of normal-untreated lymphocytes. An attempt was made to correlate the CF-induced charge redistribution with the rate of agglutination with the cationic Poly-L-lysine. Our observations indicate that the CF ligand does induce an anionic site redistribution, varying in density, both in fresh leukemic cells and in cells from a K-562 line, and does not in normal untreated and PHA-benign transformed lymphocytes. The particular pattern of anionic site redistribution observed in leukemic cells of this study is apparently phase-cycle dependent.

Acute Disease↗

Deletion of chromosome 2 is an early event in the development of radiation-induced myeloid leukemia in SJL/J mice.

In this study we have analyzed the chromosomal changes in the preleukemic phase in SJL/J mice treated with radiation and acute myeloid leukemias (AMLs) induced by radiation alone or with additional corticosteroid treatment. SJL/J mice exposed to 300 rad whole body irradiation developed a low incidence of AML (20-25%) that could be markedly increased (to 50-70%) by additional coleukemogenic treatment with corticosteroids. Partial deletion in one chromosome 2 was found in 100% of bone marrow and spleen cells of leukemic animals in both treatment modalities, whereas the age-matched controls exhibited a normal karyotype. Five types of deletion were observed according to site and size, but region D through G was the common missing part in all five types of chromosome 2 deletion. The occurrence of chromosome 2 deletion was also tested among bone marrow cells removed from 17 mice, 4 months after exposure to 300 rad whole body irradiation, long before the time when AML development is expected. About 80% of the mice tested had different levels of deleted chromosome 2 among their bone marrow population. Cytological and histological examination of bone marrow and spleen of most tested animals showed a normal hematologic picture. These results suggest that the marker chromosome is related to the process of radiation-induced initiation of AML in SJL/J mice.

Animals↗

Stromal cell effects on clonal growth of tumors.

Clonal growth of tumor cell lines originating from a variety of solid tumors was studied. The seeding efficiency of these tumors in methylcellulose medium was in the range of 0.036 to 0.177. Stromal cell lines from mouse bone marrow as well as primary stromal cells from human bone marrow stimulated the growth of HCT and oat human carcinoma cells 32-fold and 25-fold, respectively. In contrast, these stromal cells inhibited the in vitro cloning of human and mouse sarcoma cell lines. Both activities of the stromal cells diffused through agar layers and operated across species barriers. Despite the diffusable nature of the factors involved, no biologic activity was observed in concentrated conditioned media prepared in the presence or absence of serum. Human foreskin fibroblasts tested under identical conditions, could neither stimulate nor inhibit the clonal growth of tumors. This preferential growth of tumor cells in the presence of tissue specific stroma may be used as an in vitro model for the study of the role of stromal cells in tumor cell spread.

Animals↗

Granulopoiesis in aged people: inverse correlation between bone marrow cellularity and myeloid progenitor cell numbers.

Results of a study on bone marrow (BM) cytology and cellularity, BM granulocytic-macrophage colony formation (GM-CFU-C), peripheral blood (PB) colony stimulating factor (CSF) and serum lysozyme activity in 20 elderly people aged from 64 to 89 are presented. Besides slight iron deficiency anemia, no hematological abnormality was detected. No change in PB and BM differential counts was found as compared to those obtained for normal adults. The BM cellularity and colony incidence were assessed using aliquots of the same specimen. GM-CFU-C frequency ranged from 15 to 156 (average 67.5) per 2 X 10(5) BM cells seeded. The largest number of colonies was observed in hypocellular BM samples (p less than 0.002). The level of serum lysozyme activity for the entire group was significantly higher than that obtained in healthy persons up to the age of 60 (p less than 0.001). The overall results support the notion that in old age, increased proliferation of committed granulopoietic stem cells in hypoplastic areas of the BM, assure normal numbers of mature blood cells in the periphery.

Aged↗

Musculoskeletal symptoms as a presenting sign of long-standing hypothyroidism.

Muscle and joint pains and/or weakness are not usually stressed as central symptoms in hypothyroidism. Two cases of long-standing hypothyroidism presenting with prominent myopathic symptoms are described. The first patient presented with a 12-year history of proximal myopathy, arthropathy and skin abnormalities, and florid primary myxedema was diagnosed. No evidence for a systemic autoimmune process was found. The second patient had been treated with irradiation to the neck 23 years before admission and presented with clinical and laboratory signs of both proximal myopathy and hypothyroidism. Thyroid hormone replacement resulted in a complete recovery of all the musculoskeletal symptoms, with reversion to normal of the very high muscle enzyme levels in both patients. The cases presented illustrate that hypothyroidism can lead to the development of a variety of muscular, rheumatic and dermatologic syndromes easily confused with dermatomyositis or other collagen diseases.

Adult↗

Secretory piece and IgA deficiency in a patient with Waldenstrom's macroglobulinemia.

A case of a patient suffering from Waldenstrom's macroglobulinemia who developed diarrhea and mild steatorrhea is described. Laboratory studies revealed low serum IgA, intestinal secretory IgA deficiency, and small intestine bacterial overgrowth as demonstrated by the C14-cholylglycine breath test. These findings suggest that selective IgA deficiency and secretory component deficiency may be contributing factors in the development of diarrhea in Waldenstrom's macroglobulinemia.

Aged↗

Nocardia brasiliensis skin infections.

Nocardia brasiliensis skin infections were diagnosed in three patients (two with mycetoma and one with lymphocutaneous syndrome) in our hospital during the last 6 years. The mycetomas were detected in otherwise healthy Yemenite immigrants who had acquired their infection while in Yemen. The patient with the lymphocutaneous syndrome--a man with well-controlled diabetes mellitus--acquired his illness in Israel. N. brasiliensis appears to be more common in our region than previously believed. This organism should be considered a possible etiologic agent in some cases of chronic unresponsive skin infection.

Aged↗