[Heme and non-heme iron in the prevention and treatment of iron deficiency anemia].
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Biomedical subjects
Publications and source records attributed to P Reizenstein.
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Cyclosporine A (CyA) treatment of 4 patients with severe aplastic anemia, who were ineligible for bone marrow transplantation, was carried out for periods of between 12 weeks to 20 months. A normalization of Hb and bone marrow, together with a marked improvement in WBC and platelet counts, were observed in only one of these four patients. The remission was maintained for 20 months under continuous treatment. A relapse occurred only when the patient himself interrupted treatment. No serious side effects were observed with CyA doses of 4-10 mg/kg/daily and blood concentrations of 200-400 ng/ml. No significant changes in T helper/T suppressor ratios were noted during the course of CyA treatment.
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The fallout from the Chernobyl reactor resulted in radioactive fall-out in eastern Sweden leading to a ground radiation intensity of between 2 and 500 microR h-1 above the 10-15 microR h-1 background, an average external cumulative dose of about 3-4 mSv (0.3-0.4 rem) to about 1 million people, or about 3500 man-Sv (350,000 man-rem) over 50 years, or 70 man-Sv per year with a maximum dose to a few individuals of 40 mSv. The corresponding figures reported for civilians around Chernobyl is 8.6 million man-rem in 1986 and 29 million man-rem over 50 years, or 600,000 man-rem (equivalent to about 6000 man-Sv) per year. If Swedish doses are averaged over the whole population, the average is about 1 mSv or 10,000 man-Sv, or 200 man-Sv per year. The thyroid uptake of 131I is approximately 0.1-0.2 kBq (0.005 microCi) and the total body uptake of 137Cs, 1 kBq (0.03 microCi), resulting in an approximate internal dose of 0.02 mSv. If a linear dose-response curve is assumed, an increase of the normal cancer mortality incidence in the million Swedes affected by 3500 man-Sv per 50 years from 200,000 to about 200,070 can be assumed. Corresponding figures for all of Sweden are 8,000,000 inhabitants, 7000 man-Sv, 1,720,000 normal cancer deaths, and 1,720,140 expected cancer deaths. Corresponding figures reported for the population outside the 30 km evacuation zone around Chernobyl are 300,000 man-Sv, and an increase from 6,800,000 cancer deaths per 50 years to 6,806,000 cancer deaths.
In a case of prolymphocytic leukemia (PLL), receptors for interleukin-2 (IL-2R) were demonstrated by immunofluorescence with a monoclonal antibody against IL-2R. Highly purified leukemic B-cells, cultured in vitro with recombinant IL-2 (r-IL-2), responded to IL-2 with a marked increase of DNA-synthesis. Both spontaneous and r-IL-2-induced proliferation of leukemic cells were totally abrogated by the anti-IL-2R monoclonal antibody.
Thyroid uptake of 131I was measured in 130 volunteers following the nuclear power plant accident at Chernobyl in April 1986. Ninety of these volunteers had been travelling in different parts of eastern Europe at the time of or immediately after the accident while 40 persons were permanently in Sweden. Also, 28 additional healthy volunteers, living in Sweden, were chosen for a long-term follow-up of the time-course of 134Cs and 137Cs whole body uptake. The highest levels of 131I were found in persons having visited Poland (mean value 3.27 kBq +/- 3.68 SD, extrapolated to April 27) while persons that had stayed in other parts of eastern or northern Europe showed significantly lower levels (p less than 0.01). The whole body burdens of cesium radionuclides were barely detectable immediately after the accident but increased gradually throughout the observed period. After five months nine farmers from a high fallout area in central Sweden had reached mean values of 4.20 kBq (+/- 3.34 SD) of 134Cs and 137Cs while six nonfarmers from the Stockholm area showed significantly lower levels, 0.64 kBq (+/- 0.24 SD, p less than 0.05). The radiation doses from the observed amounts of iodine and cesium isotopes reported in this study reflect only a marginal addition to the already existing dose from the natural environmental background radiation.
The metabolism of arachidonic acid through the lipoxygenase pathway was studied in suspensions of fresh human bone marrow cells from eight patients with chronic myelocytic leukemia (CML) and 10 normal controls. After the cells were incubated with the calcium ionophore A23187 and arachidonic acid, a technique including reverse- and straight-phase high-pressure liquid chromatography (HPLC) was employed to isolate and detect different lipoxygenase-mediated compounds. The detected compounds included leukotriene B4 (LTB4), with its two major nonenzymatic isomers 6-trans-LTB4 and 12-epi-6-trans-LTB4 5S,12S-DHETE, and the monohydroxy eicosatetraenoic acids 5-HETE, 12-HETE, and 15-HETE. The pattern of lipoxygenase-mediated products from the bone marrows was similar to that previously described from human peripheral blood. Of eight bone marrow samples from CML patients, five expressed values above 600 ng LTB4/10(8) nucleated cells, as compared to only one out of 10 controls. In contrast, the CML patients produced significantly lower amounts of both the double-dioxygenation product 5S,12S-DHETE (56.8 +/- 16.0 ng [mean +/- SE] versus 146.1 +/- 31.3 ng; p less than 0.05) and the monohydroxy acid 12-HETE (965 +/- 351 ng versus 4390 +/- 1801 ng; p less than 0.05), indicating a 12-lipoxygenase deficiency. The present results show that leukotrienes are formed by human bone marrow cells and further suggest the existence of altered lipoxygenase activity in CML.
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The effect of retinoids on cell differentiation in the myelodysplastic syndrome was studied in short-term liquid cultures of bone marrow from 13 patients. After incubation with 13-cis-retinoic acid there was a significant decrease in the percentages of promyelocytes and in Leu-M3-binding cells. Lue-M3 is mainly a monocyte marker, and retinoids thus seem to induce a shift from monocytoid to myeloid differentiation. Patients with refractory anemia with an excess of blasts responded the most, and did also show a significant decrease in OKIa1-binding cells. Etretinate, on the other hand, did not show any differentiation-inducing activity. The results support earlier reports that retinoic acid might be useful in the treatment of the myelodysplastic syndrome. Whether this in vitro technique offers a possibility to predict the clinical outcome remains to be shown.
Interleukin-2 (IL-2) for a long time has been considered as a T-cell specific growth factor which acts through distinct surface receptors present on activated, but not on resting, T-lymphocytes. Recently it has been shown that activated murine and human B-cells also express IL-2 receptors and respond to IL-2 with an increase of DNA synthesis. Some human B-cell malignancies have been reported to react with anti-IL-2 receptor antibodies, but no response to IL-2 has been documented in these cases. Here, in five of 11 B-cell leukemia/lymphoma cases, we identified cells which not only express the IL-2 receptor, but also respond to IL-2 stimulation, as shown by a marked increase of 3H-thymidine incorporation and by differentiation of lymphoma cells. The IL-2-induced 3H-thymidine uptake was completely blocked by a monoclonal antibody to IL-2 receptor, which indicates that IL-2 acted directly through functional IL-2 receptors.
The immunological phenotypes of leukemia cell samples from 60 patients, of whom 54 had acute myeloid leukemia (AML), were assessed with a panel of monoclonal antibodies (Mabs) with specificity for the following epitopes: Epitopes associated with myeloid leukemia cells, Epitopes expressed only on immature myeloid cells (or subsets) and on monocytes, Epitopes only expressed on granulocytes or on granulocytes and mature myeloid cells (promyelocytes, myelocytes and monocytes), Epitopes on HLA-class II (DR) and HLA-class I molecules and on insulin receptors. This panel of Mabs proved useful to identify leukemia cells in blood and to assess their myeloid origin. The panel of Mabs was found also to be useful for immunophenotyping of leukemia cells. Furthermore, the analysis revealed considerable variations in the immunological phenotype of AML cells, reflecting antigenic heterogeneity within the individual leukemia cell population as well as abnormal or no expression of histocompatibility antigens and insulin receptors in some samples. Some of the Mabs bound preferentially to subgroups in the French-American-British (FAB) classification.