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Biomedical subjects

F Mitelman

Publications and source records attributed to F Mitelman.

At least 433 records · Page 24Linked to original sources

In vivo and in vitro ethylene oxide exposure of human lymphocytes assessed by chemical stimulation of unscheduled DNA synthesis.

Factory workers exposed to ethylene oxide (EO), 0.5-1.0 ppm in factory air, together with matched controls from the same factory, were examined for evidence of toxic exposure by measurement of unscheduled DNA synthesis (UDS) induced by N-acetoxy-2-acetylaminofluorene (NA-AAF) and of chromosome aberrations in peripheral lymphocytes. The total chromatid gaps plus breaks were significantly elevated and NA-AAF-induced UDS was significantly reduced in the EO-exposed group as compared with the unexposed control group. The NA-AAF-induced UDS values negatively correlated to the duration (yr) of EO exposure (r = -0.45, p less than 0.02) and the number of chromosome breaks (r = -0.61, p less than 0.05), indicating an inhibition in vivo of DNA-repair capacity by EO. These data were verified in vitro by biochemical and autoradiographic studies of EO-induced UDS in human blood cells. Above 2 mM EO, UDS was inhibited in lymphocytes whether they were cultured for 24 or 122 h after alkylation with EO. Even at the subtoxic EO dose of 0.1 mM, lymphocytes were sensitized to additional exposures of NA-AAF, so that cytotoxicity was increased to 40% compared with 5% for the controls even though UDS was unaffected. It is concluded that EO was toxic to lymphocytes, even when they were sensitized at non-toxic EO doses to the cytotoxic action of other mutagens (e.g. NA-AAF), and the cells that did survive above 2 mM EO were inhibited in their DNA-repair capacity as judged by reduced UDS.

Adult↗

Fine needle aspiration biopsy: a useful tool in tumor cytogenetics with special reference to malignant lymphomas.

A methods for chromosome analysis of malignant cells by means of fine needle aspiration biopsy has been developed. The method has some obvious advantages compared to conventional surgical biopsy. During a 1-year period 25 consecutive non-Hodgkin, non-Burkitt lymphoma biopsies from 19 patients have been studied. In 14 out of 21 lymph node biopsies chromosome analysis was successful; whereas, four biopsies of subcutaneous lymphomas were unsuccessful.

Biopsy, Needle↗

Chromosome pattern, occupation, and clinical features in patients with acute nonlymphocytic leukemia.

Chromosome banding pattern of bone marrow cells, cell morphology according to the FAB classification, and clinical finding were compared in two groups of adult patients with acute nonlymphocytic leukemia (ANLL): 52 patients occupationally exposed to chemical solvents, insecticides, or petrol products, and 110 patients with no history of occupational exposure to potential mutagenic/carcinogenic agents. Striking differences were found between the two groups: (1) Clonal chromosomal aberrations were present in 75% of exposed patients compared with only 32% in the nonexposed group. (2) Of the patients exposed to solvents and insecticides 92% had abnormal chromosomes, whereas only 29% of patients exposed to petrol products showed abnormalities; in the total material 10/13 exposed patients with normal chromosomes were exposed to petrol products. (3) The relationship between chromosomal abnormality and exposure was evident in both females and males. However, only 29% of women with an abnormal karyotype were exposed, whereas 70% of males with an abnormal karyotype were exposed. (4) The incidence of certain characteristic karyotypic abnormalities, i.e., -5/5q-, 7/7q-, +8, +21, t(8;21), and t(9;22), were decidedly more common in exposed than in nonexposed patients. At least one of these changes were present in 92% of exposed patients with aberrations, whereas in the nonexposed group the incidence was only 60%. (5) The monocytic varieties of ANLL (M4 + M5) were more common in the nonexposed patients, whereas erythroleukemia (M6) was more common in the exposed group. The predominance of abnormal karyotypes in the exposed compared to the nonexposed patients was similar in leukemia types M1 + M2 and in M4 + M5. (6) There was no difference in survival time between the two groups and the same correlation was obvious in both exposed and nonexposed patients: patients who had only abnormal metaphases had poorer prognosis than those with normal bone marrow metaphases only (6 vs 1.5 months). This correlation was obvious in patients classified as acute myeloid leukemia (AML) as well as in the monocytic varieties of ANLL.

Acute Disease↗

Micronuclei in erythropoietic bone marrow cells: relation to cytogenetic pattern and prognosis in acute nonlymphocytic leukemia.

The bone marrow karyotype and the frequency of micronuclei in erythropoietic bone marrow cells (Howell-Jolly bodies) were determined in 25 adults with acute nonlymphocytic leukemia (ANLL). Ten patients had exclusively normal diploid bone marrow cells; 11 had a mixture of normal and abnormal cells, and 4 had abnormal bone marrow metaphases only. The frequency of micronuclei ranged frm 3 to 28/2000 erythropoietic bone marrow cells (median 10). The number of micronuclei was significantly higher in patients with abnormal metaphases than in those with normal metaphases; in patients with a mixture of normal and abnormal bone marrow metaphases there was an association between the frequency of abnormal metaphases and the number of micronuclei. A striking difference in median survival time was found between patients with low and high numbers of micronuclei, irrespective of the cytogenetic bone marrow patterns. Patients with fewer than 10 micronuclei per 2000 erythropoietic bone marrow cells had a median survival of 148 days; those with more than 10/2000 had a median survival of only 34 days (0.002 less than p less than 0.02).

Adolescent↗

Incidence of Down's syndrome in Sweden during the years 1968-1977.

The incidence of Down's syndrome has been studied among children born in Sweden during the years 1968-1977. The risk for mothers of different ages of bearing such a child did not change during these years. This does not exclude that a change in incidence might have occurred in smaller areas of the country but escaped detection for statistical reasons. A higher than expected number of children with Down's syndrome were born in a few communities, which most likely is a chance event. No correlation could be detected between the incidence of Down's syndrome and a number of socioeconomic variables. The correlation with maternal age was studied in detail. There was a significant excess of males among both the newborn children with Down's syndrome and fetuses with trisomy 21 aborted after prenatal diagnosis. A similar tendency was found among the cases with a chromosome mosaicism but not among those with a translocation. Two hypotheses are put forward to explain the excess of males with trisomy 21.

Adolescent↗

Chromosomes and causation of human cancer and leukemia. XXXV. The missing Y in acute non-lymphocytic leukemia (ANLL).

The bone marrow chromosomes in six ANLL patients with a missing Y were examined. In all of six cases, the missing Y was the only chromosomal abnormality at diagnosis, and it persisted through their clinical courses. One patient had a shift from the 45,X to a 47,XX, +5, 13q + karyotype in the terminal phase of the disease. The findings indicate that the 45,X cells were not involved in further karyotypic progression, and that the leukemic process usually seemed to involve the 46,XY cell rather than the 45,X cells. Based on the data of the current study and that in the literature, it appears that the presence of missing Y in ANLL may afford a rather benign clinical course to such patients when compared to that of the ANLL patients with a missing Y. It is suggested that the age of the patients, karyotypic differences and degree of a missing Y in the marrow cells may affect the clinical course of ANLL.

Adult↗

Occupational exposure to epoxy resins has no cytogenetic effect.

Cytogenetic evaluation was performed of peripheral lymphocytes from 18 workers currently exposed to epoxy resins of the type diglycidyl ether bisphenol-A (DGEBA). 9 workers were exposed to low molecular (average MW less than 900) and 9 to high molecular (average MW about 2000) epoxy resins. The results were compared with an equal number of control individuals matched for sex and age. There was no difference in chromosomal aberration frequency between the controls and the groups exposed to epoxy resin. Thus, this study gave no indication that exposure to epoxy resin produces visible damage to the chromosomes.

Adolescent↗