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J Samuelsson

Publications and source records attributed to J Samuelsson.

43 records · Page 3Linked to original sources
PubMed1991

Further studies of the defective stimulus-response coupling for the oxidative burst in neutrophils in polycythemia vera.

We have previously reported that the chemiluminescence (CL) response of neutrophils (PMN) from patients with polycythemia vera (PV) was abnormally low when induced by surface receptor-dependent stimuli, fMLP and leukotriene B4, but normal when elicited by phorbol myristate acetate (PMA). This study documents that this discrepancy of the CL response to fMLP and PMA remained over a wide range of stimuli concentrations, was not due to iron-deficient PV cells and was also observed with the nitroblue tetrazolium assay. Moreover, another surface receptor-dependent agonist, platelet-activating factor, conferred a significantly lower CL response in PV PMN relative to controls. Treatment with alpha interferon or GM-CSF, to increase fMLP receptors, resulted in a similar enhancement of fMLP-induced CL in PV and controls. CL was normal when induced by a number of non-surface receptor-dependent stimuli. Release of lactoferrin in response to fMLP (and PMA) was normal (as was previously reported fMLP-induced chemotaxis and adherence). Thus, this defect is highly specific for oxidative metabolism, and localized to discrete step(s) of the stimulus-response coupling for fMLP, leukotriene B4 and PAF, but conceivably not due to impairment of the dynamic interaction of fMLP with its receptor.

Aged↗
PubMed1990

Elevated white blood cell synthesis of leukotriene C4 in chronic myelogenous leukaemia but not in polycythaemia vera.

Leukotriene (LT) formation was studied in ionophore A23187-stimulated white blood cell (WBC) preparations from patients with chronic myelogenous leukaemia (CML; n = 14), polycythaemia vera (PV; n = 10) and two control groups consisting of patients with non-malignant inflammatory disease (n = 4) and normal healthy donors (n = 25). The synthesized products were identified and quantitated using high-performance liquid chromatography combined with computerized UV-spectroscopy. White blood cell preparations from the CML patients produced more LTC4 (40.2 +/- 7.9 pmol/10(6) WBC, mean +/- SEM) than WBC from the healthy donors (9.0 +/- 1.8), P less than 0.0005. In contrast, the formation of LTB4 was normal and there was no increase in the total leukotriene synthesis (the sum of LTC4, LTB4, 20-OH-LTB4 and the delta 6-trans-isomers of LTB4). The ratio between leukotrienes C4 and B4 was strongly elevated in the CML group; 1.67 +/- 0.25 v. 0.37 +/- 0.07 in the controls, P less than 0.0005. No significant correlation was observed between the levels of LTC4 and the number of known LTC4 producing cells (such as monocytes, eosinophils and basophils) in the CML WBC preparations. In contrast, a correlation was found between the sum of neutrophilic granulocytes and metamyelocytes in these suspensions and the amount of LTB4 formed; r = 0.600, P less than 0.05. A number of other laboratory or clinical variables of the CML patients (including total white blood cell and platelet counts, differential counts, previous cytotoxic treatment, time from diagnosis, time from last treatment, post study survival and age) did not significantly correlate with the formation of leukotrienes. No abnormality in the production of LTB4 or LTC4 was observed in granulocyte and WBC preparations from the patients with polycythaemia vera and non-malignant inflammatory disease, respectively. The results indicate a selectively increased LTC4 producing capacity in CML.

Adult↗
PubMed1990

Treatment of myelodysplastic syndromes with retinoic acid and 1 alpha-hydroxy-vitamin D3 in combination with low-dose ara-C is not superior to ara-C alone. Results from a randomized study. The Scandinavian Myelodysplasia Group (SMG).

63 evaluable patients with myelodysplastic syndromes (MDS) and 15 with acute myelogenous leukemia (AML) were randomized between low-dose ara-C (arm A) and low dose ara-C in combination with 13-cis-retinoic acid (13-CRA) and 1 alpha-hydroxy-vitamin D3 (1 alpha D3) (arm B). 69 patients were evaluable and 18 (26.1%) responded to therapy. The addition of 13-CRA and 1 alpha D3 had no positive influence on survival of the patients, remission rates or duration of remissions. 12/27 patients in arm A and 6/29 patients in arm B progressed from MDS to AML during the course of the study (p = 0.0527). Arm B gave significantly more side-effects than arm A (p = 0.005). Therapeutic effects of 13-CRA and 1 alpha D3 on MDS is not supported by this study. However, an inhibiting effect on AML development in some MDS subgroups cannot be excluded.

Aged↗
PubMed1990

Interactions between alkylglycerols and human neutrophil granulocytes.

We evaluated whether various alkylglycerols would initiate a functional response of human neutrophils or modify responses induced by a formyl peptide (fMLP) in vitro. We found that platelet activating factor (PAF) was the most potent with regard to the ability to produce an oxidative response (assessed by cytochrome c reduction and/or chemiluminescence), followed by ET-16-OCH3. Lyso-PAF, ET-18-OCH3, batyl- and chimyl alcohols exhibited only a weak activity. PAF was also the most efficient lipid conferring a rise of intracellular calcium concentrations ([Ca2+]i). ET-16-OCH3, ET-18-OCH3 and lysoPAF were less potent, although maximal [Ca2+]i levels were similar to that of 0.1 mumol/l fMLP. The kinetics of the calcium responses were highly specific for each ether lipid. When neutrophils had been treated with PAF or ET-18-OCH3 and were subsequently stimulated by fMLP, enhancement of the oxidative response was noted. Thus, this study shows that there was an association between the ability of an alkylglycerol to initiate oxidative and calcium responses, indicating strict structure-activity relationships for these lipids.

Calcium↗
PubMed1988

Stimulus-specific defect in oxidative metabolism of polymorphonuclear granulocytes in polycythemia vera.

We investigated polymorphonuclear granulocyte (PMN) function in polycythemia vera (PV) in relation to healthy controls. PMN oxidative metabolism, assessed by chemiluminescence (CL), was significantly lower in PV patients after stimulation with leukotriene B4 (LTB4) and f-Met-Leu Phe (fMLP) (60% of control), whereas no difference in CL was seen after stimulation with phorbol myristate acetate (PMA) (120% of controls). Spontaneous and fMLP-induced PMN adherence to an albumin-coated plastic surface, as well as spontaneous migration and LTB4 - and fMLP-induced chemotaxis, were similar to controls. This suggests the presence of a stimulus-specific defect in PMN oxidative metabolism in PV.

Cell Adhesion↗
PubMed1988

Therapeutic effects of low-dose cytosine arabinoside, alpha-interferon, 1 alpha-hydroxyvitamin D3 and retinoic acid in acute leukemia and myelodysplastic syndromes.

62 evaluable patients with myelodysplastic syndromes (MDS) or acute leukemia were treated with different combinations of low dose ara-C, alpha-interferon (IFN), 1 alpha-hydroxyvitamin D3 (vit D3) and retinoic acid. The aim was to study the efficacy and toxicity of each combination. The overall rate was 44%. Of these, 50% responded favorably to the combination of IFN, vit D3 and retinoic acid (IDR), which was comparable to the response rate of 43% for low-dose ara-C. The results of the IDR treatment may be explained by additive or synergistic effects between the separate drugs in the combination. Ara-C and IDR treatment was generally well-tolerated but interferon gave more side effects than any other drug used in the study. Evaluation of the full combination of ara-C, IFN, vit D3 and retinoic acid was not possible because of toxicity. Marrow hypoplasia was infrequent (5/27 patients) in cases responding favorably to treatment. Complete remissions were not longer than partial remissions or significant responses.

Actuarial Analysis↗