Mogens Krogh Jensen

Cytogenetic effects of methotrexate on human cells in vivo: comparison between results obtained by chromosome studies on bone-marrow cells and blood lymphocytes and by the micronucleus test.

Cytogenetic studies were performed in 22 patients treated with methotrexate (MTX). In some patients, metaphases from both bone-marrow cells and peripheral blood cells were studied. In the bone-marrow preparations an increased number of structural chromosomal aberrations was present, whereas abnormalities were not observed in the peripheral blood cells. An examination of the bone-marrow chromosomes must therefore be included in the study of the possible chromosome-breaking effect of chemical agents. The results obtained with the micronucleus test and chromosome studies were compared in 10 patients treated with MTX. The micronucleus test was more sensitive than the chromosome analysis as regards the clastogenic effect of MTX.

Chromosomal banding patterns in 88 cases of acute nonlymphocytic leukemia

Abstract The chromosomal findings in 88 consecutive cases of acute nonlymphocytic leukemia (ANLL) which have been cytogenetically evaluated are reported. The chromosomes were directly prepared from bone marrow cells and studied by trypsin-Giemsa banding. Abnormal stem lines were found in 42% of the cases. Supernumerary chromosomes Nos. 6, 8 and 21, missing chromosomes 7 and Y, and structural rearrangements t(8;21) and 5q—occurred so often that nonrandom events are presumably underlying. It is shown that nonidentical marker chromosomes often have break points in common. Several vulnerable points which particularly often appear to break in structural rearrangements are located. It is pointed out and discussed that the large series of ANLL analysed with banding which have been published so far disagree concerning the frequencies of nonrandom aberrations.

Marker chromosome 14q+ in non‐endemic Burkitt's lymphoma

The chromosomal aberrations in tumor cells obtained by bone marrow aspiration from a patient with non‐endemic Burkitts lymphoma (BL) are reported. Twenty percent of the cells contained the marker chromosome 14q+ earlier described in endemic Burkitts tumors. Other marker chromosomes were found only in mitoses which did not contain the 14q+.

Cytogenetic findings in pernicious anaemia. Comparison between results obtained with chromosome studies and the micronucleus test.

To elucidate whether the micronucleus test may be a sensitive test for the demonstration of the occurrence of spontaneous structural chromosomal aberrations in human disease, bone-marrow smears and chromosome preparations were studied from ten patients with pernicious anaemia. An increased incidence of metaphases with structural chromosomal aberrations was seen in three of the patients, whereas an increased number of bone-marrow cells containing micro-nuclei was present in eight of the ten patients. The micronucleus test may thus be a rapid and sensitive test to demonstrate whether spontaneous structural aberrations of the chromosomes are present in a group of patients suffering from various diseases.

Recombinant interferon-alpha-2b treatment of hairy-cell leukaemia: experience with a low-dose schedule.

50 patients with hairy cell leukaemia (HCL) were treated with recombinant interferon (IFN) alpha‐2b 2.0 × 106 IU/m2 subcutaneously three times weekly to evaluate the efficacy of low‐dose IFN therapy in inducing and maintaining remission of the disease. At the time of this report 48 patients, of whom 22 were splenectomized, had been treated for at least 3 months and were considered evaluable for response. The median observation time on IFN‐alpha‐2b was 11 months (range 3 to 20). 4 cases with atypical disease (spongy lymphoid myelofibrosis) were also included. All patients responded to IFN. After 3 months 11/48 patients (23%) had achieved a partial remission (PR) with normalization of peripheral blood values. After 6 months 27/43 patients (63%) had achieved a favourable response; complete remission (CR) was recorded in 4 and PR in 23 patients. The proportion of patients with favourable responses (CR + PR) increased with the duration of therapy and after 12 months of therapy 23/28 (82 %) patients showed CR or PR, 9 patients (32 %) being in CR. Splenectomized patients disclosed a trend towards a more rapid response. It is concluded that IFN‐alpha‐2b is a highly effective first‐line therapy for HCL

Cytogenetic studies in patients treated with trimethoprim—sulfamethoxazole

Cytogenetic studies were performed on bone-marrow cells from 12 patients with urinary tract infections treated with trimethoprim-sulfamethoxazole (T + S). An increased number of micronuclei was presented in the patients compared with the control group, whereas structural chromosomal aberrations were not seen. The present study shows that T + S, like other folic acid antagonists, damage the human genetic material, and confirms that the micronucleus test is more sensitive than chromosome analysis in detecting a cytogenetic effect of chemical agents in man.

Deafness, urticaria and amyloidosis: a sporadic case with a chromosomal aberration.

Abstract A patient with progressive perceptive deafness, transient attacks of fever with urticaria, and amyloidosis is described. This disease complex has been reported as a hereditary entity; in our case, however, there were no similar findings in the family, except deafness. Amyloid was demonstrated in biopsy specimens from the kidney and the liver, and in the vessel walls of a duodenal biopsy specimen.

Effect of human leukocyte interferon on human lymphocytes in vitro: cytogenetic studies

Mitogen-stimulated lymphocytes from 8 healthy donors were exposed to interferon, and cytogenetic studies were preformed. The response of lymphocytes to the mitogens phytohemagglutinin (PHA), concanavalin A (con A) and pokeweed mitogen (PWM) was inhibited by interferon, whereas an increased number of structural chromosomal aberrations was not detected. Further investigations of the cytogenetic effects of interferon are needed.

Cytogenetic studies in sideroblastic anemia

Cytogenetic studies were performed on bone marrow aspirates from seven patients with acquired sideroblastic anemia. In one male patient a 45, X cell line was present in each of three bone marrow aspirates. The remaining six patients had a normal chromosome complement. The abnormal stem line in the bone marrow may be unrelated to the hematologic disorder or may indicate a neoplastic process still latent. The cytogenetic literature on sideroblastic anemia is reviewed.

Cytogenetic studies in patients treated with penicillamine.

Cytogenetic studies were performed on bone-marrow cells from 11 patients with rheumatoid arthritis treated with penicillamine. One of the patients was studied while developing a granulocytopenia and thrombocytopenia. The findings show that penicillamine had no chromosome-damaging effect as estimated by the micronucleus test and by the number of structural chromosomal aberrations.