A variant form of hypergranular promyelocytic leukaemia (M3)
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Biomedical subjects
Publications and source records attributed to C Sultan.
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Clinical and haematological features of 13 patients with secondary myelodysplastic syndromes (MDS) were studied, MDS developed subsequent to chemotherapy and/or radiotherapy for various haematological or non-haematological diseases. In six cases, the first sign was a persistently increased mean cell volume (MCV) and a macrocytosis preceding from 6 to 18 months the appearance of severe anaemia or acute leukaemia. In five cases, the initial finding was a macrocytic anaemia. Dysmyelopoiesis was a constant and prominent feature of the bone marrow smears at some time during the course of the disease. Two cases without macrocytosis at any time directly developed overt acute leukaemia.
Testosterone metabolism and dihydrotestosterone (DHT) receptor activity were studied in fibroblasts cultured from genital and non-genital tissues of 8- to 22-week old human fetuses. As early as the eighth week of gestation, DHT receptor activity was detected in non-genital skin. The binding capacity (Bmax) was greater in genital skin fibroblasts (mean +/- SD = 474 +/- 32 moles x 10--18/micrograms DNA) than non-genital skin (mean +/- SD = 124 +/- 42 moles x 10(-18)/micrograms DNA). DHT receptor binding (Bmax) was found in fibroblasts derived from testes (112 moles x 10(-18)/micrograms DNA), but not intestine (less than 10 moles x 10(-18)/micrograms DNA). The DHT receptor activity of fetal skin fibroblasts of genital origin was similar to that of fibroblasts derived from the foreskin of normal newborns. DHT receptors from fetal and newborn fibroblast cultures had similar sedimentation coefficients in sucrose density gradient centrifugation, but there were small differences in their relative affinities for 17 beta-estradiol and cyproterone. Low, but detectable 5 alpha-reductase activity was observed at 8 weeks gestation in non-genital skin fibroblasts and was present in fibroblasts from a variety of tissues of older fetuses, including testes, kidneys and lungs. The highest 5 alpha-reductase activity of 210 pg/hour/micrograms DNA was found in fibroblasts cultured from clitoral tissue from a 10-week old fetus. In all but one specimen, the 5 alpha-reduced products were either DHT or 5 alpha-androstanedione. The demonstration of 5 alpha-reductase activity and specific DHT receptors in fetal tissues suggests that the intracellular mechanism for androgen action is present in the fetus, similar to that after birth.
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The effect of DHT on skin fibroblasts proliferation was investigated by measurements of DNA concentrations and of 3H-thymidine incorporation variations. 1 nM DHT did not stimulate fibroblasts growth in either genital nor non genital skin fibroblasts. At higher concentrations, DHT inhibited cell proliferation. It can be concluded that in cell culture, fibroblasts growth is not dependent from androgen receptor content.
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Plasma prolactin was measured in six normal boys, during night sleep, with simultaneous recording of EEG for determination of the various stages of sleep. Peaks of prolactin appear clearly during cycles of rapid sleep: in prepuberty, the average of night peaks of prolactin is higher than that in post-puberty subjects. These results suggest indirectly, a participation of prolactin in prepuberty adrenal maturation.
In a 75-year-old man, the rapid development of a pancytopenia as a result to total marrow failure, in the absence of tumour or extramedullary myelopoiesis, but with a histological appearance of the marrow identical to that seen in agnogenic myeloid metaplasia led to a diagnosis of malignant myelofibrosis. The patient died 7 months after the apparent onset of the disease. The 48 other published cases are discussed. Only 17 are considered to be true cases of malignant myelofibrosis.
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The effects of 5,10-secoestra-4,5-diene-3,10,17-trione (Compound I) and 5,10-seco-19-norpregna-4,5-diene,3,10,20-trione (Compound II) on the 5 alpha-reductase activity and on the androgen receptors of normal human sex skin fibroblasts were investigated. The Vmax and Km of the transformation of testosterone to 5 alpha-reduced products was 387 pg/microgram DNA/30 min and 234 X 10(-9)M, respectively. When the inhibitors were introduced in the assay, the 5 alpha-reductase activity was markedly reduced, Compound I being a less potent inhibitor than Compound II. At 15 min, the inhibition was greater than at 30 and 60 min. The Ki for Compound I was 1.60 x 10(-6)M with a Vmax of 83 to 553 pg/microgram DNA/30 min. For Compound II, the Ki was 0.53 x 10(-6)M with a Vmax of 70 to 340 pg/microgram DNA/30 min. The inhibition was of the noncompetitive type. Studies with androgen receptors showed that Compound I had a lower affinity for the receptors than Compound II. The ID50 for 3H-DHT and 3H-T for Compound I were 42.9 x 10(-7)M and 8.6 x 10(-7)M, respectively, whereas for Compound II, they were 10.6 x 10(-7)M and 4.8 x 10(-7)M.
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Serum containing a monoclonal IgM protein from a patient with Waldenstroms' macroglobulinaemia gave intense immunofluorescent staining of kidney nuclei. The Fab mu fragments of this immunoglobulin were obtained. The IgM and Fab fragments reacted in vitro with kidney nuclei using unfixed cryostat sections of rat or mouse kidney. After treatment of the patient with chemotherapy, the monoclonal IgM disappeared, and no more antinuclear activity could be detected in the serum. The results strongly suggest that this IgM protein had antinuclear activity.
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The formation and fine structure of giant granules in neutrophil promyelocytes of a patient with a variant of acute myelogenous leukemia were investigated by electron microscopy. The patient presented with large lymph nodes and disseminated intravascular coagulation (DIC). By light microscopy, numerous giant granules, resembling those of Chediak-Higashi syndrome (CHS), were present, but Auer bodies could not be found. By electron microscopy, these giant granules were seen to be formed by fusion of azurophilic granules, as in CHS; however, they were different from the large granules of CHS, since they contained numerous microcrystalline structures like those of Auer bodies. However, the crystalline cores of these granules exhibited a periodicity different from that of Auer bodies of acute promyelocytic leukemia. This clinical and hematologic syndrome (giant granules, enlarged lymph nodes, and DIC may represent a variant of acute promyelocytic leukemia.
The authors consider the clinical and biological data of Acquired Idiopathic Sideroblastic Anemia (AISA). The physiopathology of the syndrome is discussed; the relationships between pathologic sideroblastosis, dyserythropoiesis and ferrokinetic modifications are pointed out. The associated abnormalities of granulocytic and megacaryocytic series linked AISA to other myelodysplasia.
The authors describe in this paper the considerations which led to the installation of a computer in an hematology laboratory. The different functions of the system are analyzed. Reception and identification of samples, codes for patients and analysis, print out of working lists, print out of results and monitoring of archives. A new system for differential counts is also described. Advantages of the system are discussed.
The "dU suppression" test, studying thymine-DNA synthesis from deoxyuridine is abnormal in folate and vitamin B12 deficiency, these two vitamins being involved in this reaction. We have done it in 7 cases of anaemia by folate deficiency, 12 cases of anaemia by vitamin B12 deficiency, in 3 cases of combined deficiency, in 3 cases of acute myeloïd leukaemia, 2 cases of sideroblastic anaemia and 2 cases of intoxication by antifolate. This test is very sensitive: it is abnormal even when there is an anaemia related to a vitamin deficiency with only very light morphologic abnormalities and can discriminate the cases, mainly in myelodysplastic syndromes, where folate deficiency is only an epiphenomen in the genesis of anaemia. The abnormalities of the "dU suppression" are quite corrected by added folate derivatives in folate deficiency. However, cobalamin derivatives did not correct completely the test in vitamin B12 deficiency except when a folate compound is also added. The "dU suppression" test becomes normal about one week after starting vitaminotherapy in vitamin B12 deficiency.