Supplementation with ubiquinone-10 causes cellular damage during intense exercise.
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Adult↗
Biomedical subjects
C Malm
Publications and source records attributed to C Malm.
Intensive treatment in order to minimize the Ph-positive clone in CML. Danish-Swedish CML Group.
With the rationale that a significant reduction of the malignant clone in CML might prolong time to metamorphosis, intensive treatment was given to patients < or = 55 years. Six months of hydroxyurea and high dose interferon-alpha (IFN-alpha) was followed by one to three courses of intensive chemotherapy. Patients who had a donor were allotransplanted and patients who became Ph-negative in bone marrow were autotransplanted. On 1 May 1995, 160 patients were registered in the study. Fifty-one percent of the patients who received six months IFN-alpha and hydroxyurea had a significant Ph-reduction and 5% became Ph-negative. The corresponding figures after two intensive chemotherapy courses were 47 and 28%, respectively. Twenty-seven of 30 autotransplanted patients have been analysed for Ph. Seventeen have relapsed cytogenetically, while ten are Ph-negative 1-64 + months after ABMT. BMT was performed in 59 patients. The actuarial 6-year survival from diagnosis of all 160 registered patients is 68%, which seems to be better than for age-matched historical controls.
Adolescent↗
Transforming growth factor-alpha (TGF-alpha) in human bone marrow: demonstration of TGF-alpha in erythroblasts and eosinophilic precursor cells and of epidermal growth factor receptors in blastlike cells of myelomonocytic origin.
The expression of transforming growth factor-alpha (TGF-alpha) in human differentiating leukemic cell lines and in circulating human eosinophils prompted the search for an analogous function in normal human bone marrow (BM) cells. Immunohistochemistry, using a monoclonal antibody directed to the mature form of the TGF-alpha molecule, showed TGF-alpha on the erythroblasts of normal donors. This novel property of erythroid cells was found on cells at all stages of maturation, most clearly on nucleated forms but to some extent also on erythrocytes within the BM. The presence of membrane-bound TGF-alpha on erythroblasts was confirmed by immunomagnetic cell sorting with polyclonal TGF-alpha antibodies; the recovered cells consisted almost entirely of erythroblasts. Using another monoclonal antibody directed to TGF-alpha, immunohistochemistry showed a different pattern of positive cells including eosinophilic precursor cells, in accordance with earlier findings in blood eosinophils. In addition, the TGF-alpha immunoreactivity was shown in promyelocytes and neutrophilic myelocytes. The presence of epidermal growth factor (EGF) receptor mRNA in BM cells was demonstrated by reverse transcription polymerase chain reaction, whereas EGF receptor-carrying cells were recognized by immunohistochemistry, using polyclonal antibodies directed to the cytoplasmic part of the EGF receptor. The EGF receptor-positive cell constituted about 3% of the nucleated BM cell population. It was classified as a blastlike cell of myelomonocytic origin by morphologic criteria and CD68 positivity. Our results may indicate a novel function of TGF-alpha in erythrocytic differentiation.
Antibodies, Monoclonal↗
Subcutaneous injections of 2-chlorodeoxyadenosine for symptomatic hairy cell leukemia.
PURPOSE: To evaluate the clinical efficacy and safety of 2-chlorodeoxyadenosine (CdA) when administered by subcutaneous injection to patients with symptomatic hairy cell leukemia (HCL), and to evaluate predictive factors for response. PATIENTS AND METHODS: Seventy-three patients were given CdA as a subcutaneous injection once daily for 7 days. Complete remission (CR) required normalized blood counts and the absence of B-ly 7-positive bone marrow cells by flow cytometry. CdA concentrations in plasma following the first injection were analyzed by high-pressure liquid chromatography. RESULTS: Fifty-nine patients (81%) achieved a durable CR after one (n = 55) or two courses, and 10 had a partial remission (PR). With a median follow-up duration of 20 months, no patient had a clinical relapse. Neutropenic fever that required intravenous antibiotics occurred in 28 patients (38%). No toxicity at injection sites was observed. Incomplete response was predicted by an elevated lymphocyte count and serum beta 2-microglobulin level, and by a high percentage of hairy cells in the bone marrow. Plasma CdA levels were similar to those achieved from intravenous administration. CONCLUSION: Subcutaneous injection of CdA is safe and as effective as continuous infusion without problems associated with the mode of administration. Our schedule simplifies CdA treatment and can be generally recommended.
Adult↗
Production of transforming growth factor alpha by human leukemia cells (HL-60 and U-937) during monocytic differentiation.
We have previously demonstrated that human promyelocytic HL-60 cells express transforming growth factor-alpha (TGF-alpha) during granulocytic differentiation. The present experiments were carried out in order to determine whether cells differentiated towards monocytes/macrophages will analogously express the TGF-alpha proto-oncogene product. HL-60 cells were induced to differentiate with 1 microM 1,alpha 25-dihydroxycholecalciferol (vitamin D3), and the human monocytoid cell line, U-937, was induced with 1 microM retinoic acid (RA), 0.1 microM vitamin D3, or 0.16 microM phorbol-12-myristate-13-acetate (PMA), ie experimental protocols known to induce monocyte/macrophage differentiation in these cells. In HL-60 cells, lacking constitutive TGF-alpha mRNA, vitamin D3 caused expression of the TGF-alpha gene and protein as demonstrated by Northern blot analysis and enzyme-linked immunoabsorbant assay (ELISA). In U-937 cells, showing constitutive TGF-alpha expression, RA but not vitamin D3 or PMA, caused marked increase in TGF-alpha mRNA (approximately 5-fold) and protein (approximately 3-fold) levels. In both cell lines the increase in TGF-alpha mRNA was evident within 24 h and continued throughout the observation period. Thus, it is established that differentiation of human leukemia cells towards monocytes/macrophages may be accompanied by TGF-alpha gene and protein expression in vitro. This is in conformity with the observed ability of mature activated macrophages to produce TGF-alpha.
Antigens, CD↗
[Acute dysphagia and a swollen tongue caused by temporal arteritis. Giant cell arteritis lead to necrosis].
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Acute Disease↗
Infection of donor lymphocytes with human T lymphotrophic virus type 1 (HTLV-I) following allogeneic bone marrow transplantation for HTLV-I positive adult T-cell leukaemia.
Human T lymphotrophic virus type 1 (HTLV-I) associated leukaemia has a poor prognosis even with chemotherapy. We describe a patient with adult T-cell leukaemia treated with allogeneic bone marrow transplantation from an HTLV-I negative identical sibling donor. During follow-up after bone marrow transplantation, HTLV-I could be repeatedly isolated inspite of anti-viral prophylaxis. The patient died of an acute encephalitis and HTLV-I could be detected in autopsy material from the brain. By a PCR-based technique using short tandem repeats (STRs) it was shown that the patient's haemopoiesis was of donor origin. This shows the infection of donor cells in vivo by an aetiological agent which has been implicated in the leukaemogenic process for adult T-cell leukaemia.
Bone Marrow↗
Transforming growth factor alpha expression in normal human blood eosinophils: differential regulation by granulocyte-macrophage colony-stimulating factor and interleukin-3.
We have previously demonstrated a constitutive expression of transforming growth factor alpha (TGF-alpha) in normal human blood eosinophils, both at the mRNA and protein level. This may indicate a novel function of the eosinophil, the regulation of which has not been clarified. Therefore human white blood cells (WBC) were treated with potential regulators of eosinophil function. Northern blot analysis demonstrated that human recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3) caused a time and dose-dependent 2- to 3-fold increase of TGF-alpha mRNA levels, in relation to incubation in the absence of cytokine; maximal response was attained within 4 h of incubation. In contrast, IL-5 failed to influence the expression of the TGF-alpha gene. In situ analysis of GM-CSF- or IL-3-stimulated cells showed that eosinophils remained the sole cell type expressing TGF-alpha mRNA. However, whereas GM-CSF significantly induced, within 1 h, release of immunoreactive TGF-alpha protein, IL-3 was insufficient in this respect. In conclusion, our findings indicate that expression of TGF-alpha gene and protein in normal blood eosinophils is differently regulated by GM-CSF and IL-3.
Dose-Response Relationship, Drug↗
Intensive treatment in order to minimize the Ph-positive clone in chronic myelogenic leukemia (CML). Swedish CML-group.
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Adult↗
Heart failure after parvovirus B19 infection.
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Adult↗
Expression of the transforming growth factor alpha protooncogene in differentiating human promyelocytic leukemia (HL-60) cells.
The process of myeloid differentiation in human promyelocytic leukemia cells (HL-60) is accompanied by the coordinate expression of numerous protooncogenes. To investigate the expression of transforming growth factor alpha (TGF-alpha) in myeloid differentiation, HL-60 cells were induced to differentiate into granulocytes with 1.25% dimethyl sulfoxide, 0.2 microM all-trans retinoic acid, or 500 microM N6,O2-dibutyryladenosine-3'5'-cyclic monophosphate or differentiated along the monocyte/macrophage pathway with 0.1 microM phorbol-12-myristate-13-acetate. Using Northern blot analyses, TGF-alpha transcripts were detected within 24 h of treatment in cells differentiating toward granulocytes; maximal levels of gene expression were reached after 3 days or later and remained essentially constant throughout the observation period. These cells released TGF-alpha protein, as demonstrated by analysis of the incubation medium. In contrast, no TGF-alpha RNA or protein was detectable in HL-60 cell cultures when induced with phorbol-12-myristate-13-acetate. Epidermal growth factor receptor transcripts could not be detected either in undifferentiated or in differentiated HL-60 cells; therefore it appears as if an autocrine loop involving TGF-alpha in HL-60 cells is unlikely. In conclusion, the results demonstrate, for the first time, the expression of TGF-alpha in human granulocyte precursor cells. Our findings may indicate novel regulatory pathways in hematopoiesis.
Cell Differentiation↗
Intensive treatment in order to minimize the Ph-positive clone in chronic myelogenic leukemia.
Several studies indicate that interferon (IFN) treatment, intensive chemotherapy and autologous bone marrow transplantation (ABMT) effectively reduce the Ph-positive clone in Chronic Myelogenic Leukemia (CML). In the present study on patients < or = 55 years, we have combined these three treatment modalities. The aim of the study was to eliminate or minimize the Ph-positive clone to see whether a status of minimal residual or Ph-negative disease could be maintained for a longer period of time. After diagnosis, patients received interferon (IFN-a-2b) and hydroxyurea (HU) to keep the white blood cell (WBC) and platelet count below 2-4 and 100-150 x 10(9)/l, respectively. After six months of treatment, Ph-analysis was performed. Patients with Ph-positive cells in bone marrow then received 1-3 courses of intensive chemotherapy. In patients Ph-negative after two courses, bone marrow was harvested and used for ABMT. After a third course, patients with up to 50% Ph-positive metaphases were accepted for ABMT. As of January 1, 1993, 97 patients were registered in the study. Six months of IFN+HU reduced the percentage of Ph-positive metaphases in 57% of the patients (7% became Ph-negative). The corresponding figures after two intensive cytotherapies were 70% (40% Ph-negative). Eighteen patients were autotransplanted. Seven have relapsed with Ph-positivity 3-22 months after ABMT, while nine are Ph-negative at 1-32+ months after ABMT (two not yet analyzed). Seventeen patients are alive and well, while one died one month after ABMT due to interstitial pneumonia.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Clinical, neurophysiological and immunological evidence of polyneuropathy in patients with monoclonal gammopathies.
In this study we estimated the prevalence of polyneuropathy (PN) in patients with monoclonal gammopathies. 31 patients with monoclonal gammopathies (19 with monoclonal gammopathy of uncertain significance (MGUS), 10 with multiple myeloma (MM), and 2 with Waldenström's macroglobulinemia), were studied by clinical and neurophysiological examination, blood tests to exclude other causes of PN, ELISA assays to detect antibodies to peripheral nerve myelin (PNM), and antibodies to myelin associated glycoprotein (MAG). 11 of 31 patients (36%) had a clinical PN, 3 (10%) had a probable PN (signs but no symptoms), and 4 (13%) had a subclinical PN (only neurophysiological signs of PN). Thus, in total 18 patients (58%) had some form of PN, in contrast to an age-matched control group (n = 33) where only 2 persons (6%) had some form of PN; 1 had a probable PN and 1 had a subclinical PN. 3 patients had anti-PNM and anti-MAG antibodies of IgM isotype, all 3 patients showing a demyelinating PN. The remaining patients with PN had a mild or moderate distal PN. One patient had a myelopathy and 1 had amyotrophic lateral sclerosis (ALS). IgM isotype of the M-protein was associated with a high risk of clinical PN (5 out of 6 (83%)), in contrast to IgG (5 out of 18 (28%)) and IgA (1 out of 6 (17%)). We conclude that PN is a common finding in patients with monoclonal gammopathies, but only some of them are of the demyelinating type and associated with antibodies to PNM or MAG.
Adult↗
Production of transforming growth factor alpha by normal human blood eosinophils.
Transforming growth factor alpha (TGF-alpha) is a pleiotropic factor mediating numerous cellular responses in normal and transformed cells. This includes differentiation, proliferation, migration, and formation of extracellular matrix. TGF-alpha has been demonstrated in circulating eosinophils from the idiopathic hypereosinophilic syndrome and in differentiating promyelocytic leukemia cells in vitro. Whether TGF-alpha production also occurs in normal human blood cells is not known. Northern blot analysis showed that normal human white blood cells consistently expressed the TGF-alpha gene in 47 out of 47 donors. Cell preparations enriched in mononucleated cells, and devoid of granulocytes, showed no TGF-alpha mRNA. In situ hybridization experiments assigned the TGF-alpha gene expression to the eosinophils; 100% of the eosinophils and no other cell types were specifically recognized by the complementary human TGF-alpha riboprobe. White blood cells, incubated at 37 degrees C for up to 6 hours, released immunoreactive TGF-alpha to the incubation medium, as determined by ELISA. In contrast, no TGF-alpha protein was detected in the incubation medium of mononuclear cells. It is concluded that TGF-alpha is constitutively produced and released by normal human blood eosinophils. TGF-alpha provided by eosinophils, may participate in the inflammatory reaction by interacting with mesenchymal and epithelial cells, thus promoting fibrosis or neovascularization.
Eosinophils↗
Clinical impact of breakpoint position within M-bcr in chronic myeloid leukemia.
We have analyzed the M-bcr breakpoint position in 133 Philadelphia-positive chronic myeloid leukemia patients and correlated the findings with clinical, hematologic, and cytogenetic data. We also investigated the splicing pattern of the BCR-ABL mRNA in 30 patients, using reverse transcriptase PCR. No statistically significant differences were found between breakpoint position within M-bcr and clinical parameters at diagnosis, the karyotypic evolution pattern, or the leukemic phenotype during blast crisis. Furthermore, the breakpoint position within M-bcr did not correlate with the duration of chronic phase or survival time. When the splicing pattern of the BCR-ABL mRNA was compared with the results of the genomic breakpoint mapping, it was found that approximately 60% (8/14) of the patients with a 5' break expressed b2a2 fusion mRNA, whereas all patients (10/10) with a 3' break expressed b3a2 BCR-ABL mRNA.
Adolescent↗
Ig-secreting cells pass the blood-brain barrier: studies on kappa and lambda light chain secreting cells in plasma cell dyscrasia.
To study if immunoglobulin (Ig)-secreting cells actively pass the blood-brain barrier (BBB), 15 patients with monoclonal gammopathy underwent bonemarrow (BM) iliac crest aspiration biopsy, peripheral blood (PB) sampling and cerebrospinal fluid (CSF) analysis. With an enzyme-linked immunospot assay we investigated the number and ratio of mononuclear cells secreting Ig with kappa and lambda light chains in the three different compartments. A statistically significant (P < 0.05) correlation between the ratio of Ig kappa/lambda-secreting cells in CSF, PB and BM was found. The frequency of kappa and lambda (i.e. Ig in total) secreting mononuclear cells, of the same Ig class as the paraprotein, per 10(4) mononuclear cells was higher in BM (median 2.16%, range 0.43-9.28%) compared to CSF (median 0.44%, range 0.05-9.25%) and in CSF compared to PB (median 0.12%, range 0.02-0.96%). The proportion of all mononuclear cells with Ig kappa and lambda light chain (i.e. Ig) secretion was on average 5-fold greater in CSF compared to PB and 11-fold greater in BM compared to PB. The present study indicates that paraprotein-secreting cells preferentially pass from PB to CSF.
Aged↗
Trisomy 13 as a primary chromosome aberration in acute leukemia.
Four patients with acute leukemia displayed trisomy 13 as the primary chromosome abnormality. The two patients with acute nonlymphocytic leukemia FAB-type M1 (ANLL-M1) had the karyotypes 47,XY,+13/48,XY,+13,+13 and 47,XX,+13, a patient with the hypogranular form of ANLL M3 had 47,XX,+13, and the fourth patient, who had acute undifferentiated leukemia (AUL), had the karyotype 47,XY,+13/48,XY,+8,+13. Including these four cases, a total of 24 hematologic neoplasms with an extra chromosome 13 as the sole aberration have now been reported. Except for the AUL, all have been of myeloid origin--20 ANLL, one myelodysplastic syndrome, and two chronic myeloproliferative disorders. Trisomy 13 as the sole acquired karyotypic abnormality therefore seems to be strongly associated with myeloid differentiation of the neoplastic cells and with a differentiation block leading to acute leukemia.
Acute Disease↗
Mitoxantrone and cytarabine versus daunorubicin and cytarabine in previously untreated patients with acute myeloid leukemia.
A total of 44 adults aged 18-78 years were allocated to an open randomized study whose aim was to compare the efficacy and toxicity of mitoxantrone with those of daunorubicin in previously untreated patients presenting with acute myeloid leukemia. In one arm, induction treatment consisted of mitoxantrone plus cytarabine given on a 3- plus 7-day schedule. Post-induction treatment consisted of two courses of mitoxantrone plus cytarabine given on a 2- plus 5-day schedule. In the control arm, mitoxantrone was replaced by daunorubicin. In all, 14 of 21 eligible and evaluable patients in the mitoxantrone arm achieved a complete remission (CR). In the control arm, 14 of 20 subjects attained a CR. The median survival was 365 days for patients randomized to mitoxantrone-cytarabine and 401 days for those given daunorubicin-cytarabine. The efficacy and toxicity of mitoxantrone were similar to those of daunorubicin.
Acute Disease↗