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J Ellegaard

Publications and source records attributed to J Ellegaard.

At least 19 recordsLinked to original sources
PubMed1995

[Erythropoiesis in myelodysplastic syndrome detected by multiparameter flow cytometry].

By staining human bone marrow cells with a monoclonal antibody reacting with surface antigens on erythroid precursor cells (AS-E1) and with propidium iodide reacting with nuclear DNA, we have evaluated the proliferative activity of erythropoiesis in patients with myelodysplastic syndromes using flow cytometric analysis. Comparing 36 patients (13 RA/RAS, 13 RAEB, 10 RAEB-t) with seven normal controls, significant differences in both the percentage of erythroid precursor cells and the fraction of these cells in the S or S-G2M-phase of the DNA cell cycle between the four groups were found. Since neither the percentage of erythroid precursor cells nor their fraction in S or S-G2M phase alone was found to characterize their proliferative activity, we calculated the proliferative fractions of the erythroid cells, i.e. the number of the erythroid precursor cells in S or S-G2M related to all bone marrow cells in S or S-G2M phase. Applying these parameters, we found significantly increased proliferative fractions of erythroid precursor cells in the RA/RAS patients compared to the normal controls (p-0.03 and 0.002 respectively), as well as a highly significant decrease with disease progression.

Cross-Sectional Studies↗
PubMed1995

Acyclovir given as prophylaxis against oral ulcers in acute myeloid leukaemia: randomised, double blind, placebo controlled trial.

OBJECTIVES: To evaluate (a) the prophylactic effect of the antiherpetic drug acyclovir on oral ulcers in patients with acute myeloid leukaemia receiving remission induction chemotherapy and thus (b), indirectly, the role of herpes simplex virus in the aetiology of these ulcers. DESIGN: Randomised, double blind, placebo controlled trial. SUBJECTS: 74 herpes simplex virus seropositive patients aged 18-84. Thirty seven patients received acyclovir (800 mg by mouth daily) and 37 placebo. The patients were examined daily for 28 days. MAIN OUTCOME MEASURES: Occurrence of herpes labialis, intraoral ulcers, and acute necrotising ulcerative gingivitis. RESULTS: The two populations were comparable in age, sex, type of antineoplastic treatment, and history of herpes labialis. Acute oral infections occurred in 25 of the acyclovir treated patients and 36 of the placebo treated patients (relative risk 0.69 (95% confidence interval 0.55 to 0.87)). This difference was due to a reduction in the incidence of herpes labialis (one case versus eight cases; relative risk 0.13 (0.02 to 0.95)), intraoral ulcers excluding the soft palate (one case versus 13 cases; relative risk 0.08 (0.01 to 0.56)), and acute necrotising ulcerative gingivitis (one case versus eight cases; relative risk 0.13 (0.02 to 0.95)). However, ulcers on the soft palate were diagnosed with similar frequency in the two groups. Isolation of herpes simplex virus type 1 in saliva was reduced from 15 cases in the placebo group to one case in the acyclovir group (relative risk 0.07 (0.01 to 0.48)). CONCLUSION: Intraoral ulcers excluding the soft palate are most often due to infection with herpes simplex virus, whereas ulcers on the soft palate have a non-herpetic aetiology. The findings suggest that acute necrotising ulcerative gingivitis may also be due to herpes simplex virus. Prophylaxis with acyclovir should be considered for patients with acute myeloid leukaemia during remission induction therapy.

Acute Disease↗
PubMed1995

Differential expression levels of the heat shock protein 27 isoforms in pediatric normal, nonleukemic and common acute lymphoblastic leukemia B-cell precursors.

Heat shock protein 27 (hsp27) may function as a regulator of microfilament dynamics and may participate in signal transduction pathways of different cell growth regulators, with the mitogen-activated protein kinase-activated protein (MAPKAP) kinase 2 being a major enzyme responsible for its phosphorylation. Using two-dimensional gel electrophoresis, we have compared the expression levels of two hsp27 isoelectric variants (hsp27 isoforms) M2 (molecular weight, 26 kD; isoelectric point, 6.02) and M3 (molecular weight, 26 kD; isoelectric point, 5.60) in pediatric bone marrow CD19+CD10+B-cell precursors (BCPs) purified from either common acute lymphoblastic leukemia (c-ALL) patients, normal donors, or non-c-ALL patients. Compared with normal BCPs, we found increased hsp27 expressions (M2 isoform) (by a factor 5 to 9 of mean level) in c-ALL as well as in non-c-ALL (nonleukemic) precursors. Though increased phosphorylation of hsp27 (M3 isoform) was observed in BCPs from c-ALL patients at relapse (by a factor 3 of mean level compared with normal BCPs and precursors from c-ALL at diagnosis), which might represent a differential enzymatic activity, this was not distinguishable from that of non-c-ALL patients. Therefore, our studies suggest constitutive differences of hsp27 isoforms between pediatric leukemic BCPs and their relatively low-expressing, immunophenotypically normal bone marrow counterparts. In light of the occasional and possibly transient increase of hsp27 expression during nonleukemic BCP differentiation and the possible role of hsp27 in signal transduction to microfilaments, these differences might be of considerable biologic interest and of importance in future studies of regulated normal or dysregulated leukemic hematopoietic cellular differentiation.

Adolescent↗
PubMed1995

Evaluation of transfusional iron overload before and during iron chelation by magnetic resonance imaging of the liver and determination of serum ferritin in adult non-thalassaemic patients.

The ability to quantitate transfusional iron overload is crucial for determining the need for and the efficacy of chelation therapy in patients with long-standing transfusion-dependent anaemias. We evaluated the usefulness of some indirect measures of iron overload in estimating the iron concentration in the liver--the most important iron storage organ--in 26 non-chelated adult non-thalassaemic patients. Liver iron concentration was determined non-invasively by magnetic resonance imaging (MRI). The standard error of the estimated liver iron concentration was 80 mumol Fe/g dried liver tissue when using the number of transfused blood units, and 93 mumol Fe/g when using a serum ferritin assay. Follow-up in 11 patients (12-48 months) revealed that serum ferritin is a poor measure of the liver iron concentration during iron chelation. However, this discrepancy was individually different and seemed to be dependent on the erythropoietic marrow activity. By monitoring the liver iron concentration by MRI, we compared the efficacy of chelation with desferrioxamine given either by subcutaneous continuous infusions or by bolus injections. Depletion of liver iron stores could be achieved efficiently by both regimens.

Adolescent↗
PubMed1994

A factor encoded by 7q31 suppresses expansion of the 7q- clone and delays cytogenetic progression.

Deletion of part of chromosome 7q (7q-) is a consistent aberration in human acute leukemias and myelodysplasias, especially in patients with a history of genotoxic exposure. The deletion is usually associated with a short survival. Loss of a number of different 7q segments has been described, but still it is not known whether different deletions imply differences in survival. We have investigated the possible importance of loss of different segments in 77 7q- patients studied with high-resolution banding. Thirty-six were examined in our laboratory and 41 were published cases. We found that when the 7q- marker contained the 7q31 band, the 7q- clone was smaller than when the band had been lost (p = 0.011), and the patients survived longer (p = 0.004). Further, karyotypes with complex aberrations were less frequent (p = 0.012). These results indicate that genetic information in 7q31 delays cytogenetic and clinical progression of myeloid disease with 7q-. Our results do not tell, however, whether this is due to direct tumor suppressor activity of a 7q31 gene or due to a more indirect effect.

Adolescent↗
PubMed1994

Non-invasive assessment of tissue iron overload in the liver by magnetic resonance imaging.

We investigated the clinical usefulness of a standard magnetic resonance imaging (MRI) system for non-invasive determination of the liver iron concentration in 38 patients with iron overload and 15 normal controls by measurement of the signal intensity ratio between liver and skeletal muscle (SIR). However, SIR was found dependent on the applied repetition time (TR) of the MRI system, which led us to investigate this relationship in autopsy material of liver and muscle tissue specimens with various iron content. Based on these results, adjustment of SIR measurements to a constant value of TR was achieved. By use of this technique we found a close correlation between MRI and chemically determined liver iron concentration (r2 = 0.98) as well as the serum ferritin concentration (r2 = 0.86). The reproducibility was sufficiently good for the use of MRI in the follow-up of iron reductive treatment. The use of iron store parameters in serum was found insufficient as indicators of endpoint for venesection therapy, if 20 mumol Fe/g dry weight was applied as the upper reference limit of the liver iron concentration. It is concluded that MRI based on SIR measurements offers a precise and reproducible non-invasive method for the determination and follow-up of iron overload within a wide range of liver iron concentrations. Our findings may increase the clinical use of MRI in haematological patients with iron overload.

Bloodletting↗
PubMed1994

The effect of iron overload and iron reductive treatment on the serum concentration of carbohydrate-deficient transferrin.

The concentration of carbohydrate-deficient transferrin in serum (CDT) has been used as a reliable indicator of recent alcohol consumption. We have investigated the utility of this laboratory test in 20 patients with hereditary haemochromatosis (HH) by simultaneous evaluation of serum concentrations of liver transaminases, gamma-glutamyl transpeptidase, iron, transferrin and assessment of the liver iron concentration by magnetic resonance imaging. 11 patients were re-examined during iron depletion with phlebotomies. In all 11 patients intensive but not maintenance iron removal was associated with an increase in serum CDT, in three patients even to levels above the reference range. The mean serum CDT increased from 8.5 (SD 2.2) U/l to 16.6 (SD 7.2) U/l (P < 0.001). Iron mobilization from the liver was found particularly responsible for the increase in serum CDT. Independent of this finding we found a significant semi-logarithmic correlation (r = -0.77, P = 0.009) between the MRI determined liver iron concentration and serum CDT in the patients not on iron depletion. Our findings indicate that the utility of serum CDT as a measure of alcohol consumption in patients with HH may be compromised, especially during intensive iron depletion.

Adult↗
PubMed1993

Differences in relative DNA content between human peripheral blood and bone marrow subpopulations--consequences for DNA index calculations.

By sequentially staining for leukocyte differentiation antigens with monoclonal antibodies and for stainable DNA content with propidium iodide, we have evaluated the DNA ratios of normal peripheral blood and bone marrow subpopulations. In 19 peripheral blood samples the relative DNA content of the monocytes was higher than that of other subpopulations, with highly significant differences between the DNA ratios of the CD14+ monocytes, on the one hand, unlabeled controls, CD3+ T-lymphocytes, and CD20+ B-lymphocytes, on the other. In bone marrows from 16 healthy volunteers, the relative DNA content of the myelomonocytic subpopulations was higher than that of the T-lymphocytes with significant differences between the CD3+ lymphocytes, on the one hand, and the CD14+ monocytes, the CD13+ and CD33+ immature myeloid, the NAT9+ mature myeloid, and the AS-E1+ nucleated erythroid subpopulation, on the other. Since a mixture of peripheral blood mononuclear cells or T lymphocytes from healthy volunteers is often used as an external standard for DNA ploidy determinations, these data suggest that such a procedure could result in an overestimation of the DNA indices of most of the bone marrow subpopulations. Instead, we suggest the use of the DNA ratio of the CD14+ subpopulation from peripheral blood as standards for ploidy determinations for the myeloid bone marrow subpopulations.

Antibodies, Monoclonal↗
PubMed1993

Synergistic and antagonistic effects of myeloid growth factors on in vitro cellular killing by cytotoxic drugs.

The effect of stimulating acute myeloid leukemia blast cells with a combination of growth factors (G-CSF, GM-CSF, and IL-3) on cellular resistance to the antileukemia drugs Ara-C, daunorubicin, aclarubicin, and mitoxantrone was studied. For assessment of in vitro cellular drug resistance the MTT assay was employed. Stimulated cells showed enhanced sensitivity to Ara-C (p < 0.02), whereas a significant increase in cellular drug resistance to daunorubicin (p < 0.02) was observed. Variable and statistically non-significant changes in drug resistance to aclarubicin and mitoxantrone was induced by stimulation of the blast cells. We conclude on the basis of these observations that myeloid growth factors should be used with caution in combination with daunorubicin in AML treatment until further confirmatory evidence has been presented by other investigators.

Aclarubicin↗
PubMed1993

Optimization of a method for simultaneous analysis of cell surface phenotype and cell cycle in human bone marrow and peripheral blood leukocytes by flow cytometry: the value of both internal and external standards.

Three different methods for the simultaneous analysis of surface phenotype and DNA quantification were compared. One method, involving the fixation of cells in 70% ethanol, was convincingly superior, both with regard to the CV of the G0G1 peak and the intensity of the DNA labelling. Furthermore, the correlation between the surface antigen densities before and after fixation were high. Experiments evaluating the intraday and the interday variation of the DNA ratio (the mean channel of the G0G1 peak of the sample divided by the mean channel of the G0G1 peak of chicken erythrocytes), documented the former to be small, with S.D. values varying from 0.0 to 0.016, while the latter were considerably higher with S.D. values varying from 0.077 to 0.123. Since the intraday variation of the DNA ratio was consistently low and the interday variation strongly correlated to the position of the red fluorescence test beads, it was possible to minimize the interday variation of the DNA ratio, by calculating the DNA index as the ratio between the DNA ratio of the sample and that of an external control (buffy coat leukocytes). Analyzing normal bone marrow and calculating the DNA index (DI) on the basis of these ratios, the confidence limits of the DI were decreased by more than half the values obtained when DI calculation was based solely on an internal standard, thereby making subsequent ploidy determinations of patient samples more precise. We conclude that this setup of internal and external standards allows accurate determinations of DNA aneuploidy even in an assay where whole cells labelled for surface antigen and DNA content are analyzed.

Animals↗
PubMed1992

[Granulocyte-macrophage colony-stimulating factor. Treatment of patients with highly malignant lymphomas and acute lymphoblastic leukemias after autologous bone marrow transplantation].

We have evaluated the effect of intravenous infusions of granulocyte-macrophage colony-stimulating factor (GM-CSF) in ten patients undergoing autologous bone marrow transplantation after total body irradiation (11 Gy) and cyclophosphamide (120 mg/kg) conditioning for malignant lymphomas or acute lymphoblastic leukaemias. Mild side effects related to GM-CSF were seen in six patients, of whom one chose to discontinue treatment. Compared to a historic control group consisting of six patients treated with an identical conditioning regimen, a tendency was seen towards a more rapid neutrophil regeneration and a decreased need for erythrocyte transfusions. Moreover, a statistically significant improvement in thrombocyte related parameters was demonstrated. In contrast, there were no significant differences in severe toxicity, days on i.v. antibiotics, septic episodes or duration of hospitalization. In conclusion, it seems that GM-CSF treatment is of value in patients undergoing AKMT.

Adolescent↗
PubMed1992

Induced and down-regulated proteins in the human cultured hairy cell leukemia line JOK-1 and the Burkitt's lymphoma cell line Daudi during incubation with interferon-alpha: a kinetic study.

To elucidate the mechanism of action of interferon-alpha (IFN-alpha), the effect on cell proliferation and protein synthesis in the human hairy cell leukemia line JOK-1 and the Burkitt's lymphoma cell line Daudi were investigated. While Daudi cells were inhibited in proliferation and in total protein synthesis, no effect was seen on JOK-1 cells. However, high-resolution two-dimensional gel electrophoresis showed that four polypeptides were induced in JOK-1 cells after IFN-alpha incubation, while an additional 11 were induced and two down-regulated in Daudi cells. Kinetic studies revealed that the changes in JOK-1 cells were only temporary (within 8-16 h) and small to moderate in magnitude (less than four-fold). In Daudi cells, the changes for two of these polypeptides were early (within 2 h), for most of them prolonged (at least 24 h), and for three of them of great magnitude (between 6- and 30-fold). Quantitative analytical assessments indicated that four IFN-alpha-inducible polypeptides, present in low amounts of untreated cells, were highly expressed only in sensitive Daudi cells upon IFN-alpha treatment. This observation might indicate a role for these polypeptides in the inhibition of cell proliferation in Daudi cells. Furthermore, six of the other IFN-alpha-modulated polypeptides were synthesized constitutively in JOK-1 cells at levels comparable to those achieved in IFN-alpha-treated Daudi cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Burkitt Lymphoma↗
PubMed1992

Gingival status during chemical plaque control with or without prior mechanical plaque removal in patients with acute myeloid leukaemia.

The purpose of the study was to evaluate the effect of a mouthrinse regimen comprising both chemical plaque control and mechanical plaque removal. 20 adult patients with acute myeloid leukaemia were assigned to one of the following 2 regimens: (1) (group 1) mouthrinse twice daily with a 0.1% chlorhexidine solution; or (2) (group 2) the same regimen, but preceded by mechanical removal of plaque and calculus on day 1. All patients were followed for 28 days from the initiation of remission-induction therapy. In group 2, the plaque scores remained lower than those of group 1 throughout the study, although only 3 patients remained completely free of plaque after 28 days. Gingival inflammation as judged by bleeding scores remained unchanged in group 1, whereas in group 2, the degree of inflammation was reduced from 52% (median value) on day 1 to 31% (median value) on day 28. The bleeding scores were also lower in group 2 (31%) than in group 1 (60%) on day 28. No differences were found between the 2 groups with respect to the occurrence of other oral infections. It is concluded that chemical plaque control with chlorhexidine should be preceded by mechanical removal of plaque and calculus, when used in patients with acute myeloid leukaemia and thrombocytopenia.

Aclarubicin↗
PubMed1992

Hybrid acute leukemia: therapeutical implications of immunological phenotyping.

We phenotyped blood and bone marrow cells from a patient with acute Ph1+ acute leukemia longitudinally during the four months he received intensive chemotherapy. At presentation this case of biphenotypic acute leukemia had two immunologically different types of blast cells, one expressed CD10 (CALLA), CD13 (MY7) and CD33 (MY9) but lacked CD20 (B1), the other type expressed no CD10 or CD33. The phenotype, during AML induction therapy, changed to a more CD10+, CD20+ ALL one. ALL therapy based on these findings induced improvement in bone marrow function but the patient died of septicemia at day 134. The use of concomitant immunophenotyping (IP) and cell cycle analysis had shown proliferation advantage of the more lymphoid malignant cells. These results suggest that it is possible to induce lineage-associated changes in the phenotype of hybrid malignant cells and that these leukemias might be treated best according to longitudinal immunophenotyping of the blast cells.

Adult↗
PubMed1991

Solitary expression of CD7 among T-cell antigens in acute myeloid leukemia: identification of a group of patients with similar T-cell receptor beta and delta rearrangements and course of disease suggestive of poor prognosis.

In a series of 100 acute myeloid leukemia (AML) patients defined by cytochemistry and immunophenotyping, 20 expressed T-lymphocyte associated antigens on the surface of their blasts. While 15 expressed two or more T-cell antigens, five were found to express only CD7. All patients belonged to the French-American-British type M4, and four were under the age of 40. Despite intensive chemotherapy, four never obtained a complete remission and the fifth died of relapse after an allogenic bone marrow transplantation. While 12 randomly selected T-cell antigen negative AML patients showed only few rearrangements in Ig- or T-cell receptor (TCR) genes, such genetic alterations were demonstrated in four of five patients for the TCR delta gene and in all patients for the TCR beta gene. Interestingly, DNA fragments of similar size were demonstrated in three of five patients for both the beta and delta genes. These data suggest that the solitary presence of CD7 among T-cell antigens in otherwise clearcut AML cases identifies a group of patients with similarities in antigen receptor gene configuration as well as outcome.

Acute Disease↗