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Biomedical subjects

T Olofsson

Publications and source records attributed to T Olofsson.

At least 73 records · Page 4Linked to original sources
PubMed1981

The prognostic significance of in vitro bone marrow growth pattern in acute non-lymphocytic leukaemia.

The growth pattern of bone marrow cells in agar culture was studied in 56 patients with untreated acute non-lymphocytic leukaemia. 4 different growth patterns were recognized: (A) colony and cluster formation, (B) growth of small clusters (3-20 cells) only but less than 600/10(5) cells, (C) growth of small clusters only but more than 600/10(5) cells, and (D) no growth in vitro. Patients in group A and B had a significantly higher remission rate (23/34) than patients in group C and D (3/22). This was true also when only patients below 60 years of age were considered. The median survival time of patients in group A and B was 7.3 months and 9.4 months, and in group C and D 4.0 months and 3.3 months. Identical growth patterns were found for marrow and blood cells in 21 of 27 patients studied and the number of clusters in blood and marrow showed a significant correlation (r = +0.96, P less than 0.001). The mean 3H-labelling index (LI) of myeloblasts determined in 32 patients was 14.8 +/- 7.8% (SD). Patients with LI below 15% tended to have a higher remission rate than patients with LI above 15%. It is concluded that the in vitro growth pattern at diagnosis of bone marrow cells from patients with ANLL is of value in detecting patients with a poor response to current therapeutic protocols. Such information could possibly lead to alternative cytostatic regimes in these patients.

Acute Disease↗
PubMed1981

Characterization of mononuclear blood cell-derived differentiation inducing factors for the human promyelocytic leukemia cell line HL-60.

A search was made for physiologically produced differentiation inducing factor(s) (DIF) for the human promyelocytic leukemia cell line HL-60. Mononuclear blood cells, when stimulated with various mitogens, produced DIF, which induced differentiation of HL-60 into phagocytizing nitro blue tetrazolium reducing cells with the morphologic characteristic of granulopoietic or myelomonocytic cells. Induction of differentiation occurred equally well in serum-containing and serum-free media. Protein synthesis was necessary for elaboration of DIF, which seems to be of a protein nature inasmuch as it is destroyed by proteases. Gel chromatography showed that one or two species of DIF with apparent molecular weights of 40,000 and 25,000 were produced, depending on the type of mitogen used. At least the 40,000-molecular weight DIF was distinct from the colony stimulating activity (CSA), which was produced simultaneously. Our results suggested a role of lymphocytes and/or monocytes for modulation of myelomonocytic hematopoiesis not mediated by CSA. The physiologic importance remains, however, to be demonstrated.

Cell Differentiation↗
PubMed1980

N-acetoxy-2-acetylaminofluorene induced unscheduled DNA synthesis of granulopoietic precursor cells in chronic myeloid leukemia.

Studies on N-acetoxy-2-acetylaminofluorene (NA-AAF) induced unscheduled DNA synthesis (UDS) of granulopoietic cells were performed in patients with chronic myeloid leukemia (CML). Sequential studies were carried out in some patients. Both biochemical and autoradiographic methods demonstrated that [3H]dT was incorporated into nonreplicating DNA of immature granulopoietic cells after NA-AAF damage and the 2 methods significantly correlated to each other (r = 0.63, n = 19). NA-AAF induced DNA synthesis was lower for myeloblasts than promyelocytes and myelocytes. Biochemically determined NA-AAF induced UDS was higher for immature granulopoietic cells in blood than in marrow. Sequential studies on granulopoietic blood cells suggested that phases of accelerated leukocytosis in CML can be preceded by increases of NA-AAF induced UDS. Whether increases in NA-AAF induced UDS relates to an amplification of repair enzymatic capacity closely correlated to the cellular replication capacity, or whether it reflects an increased sensitivity to DNA damage induction and the consequences thereof, was not resolved in this study. Nevertheless these results are consistent with the hypothesis that increases in NA-AAF induced UDS signal the evolution during chronic phase CML of cell populations of increasing malignancy which escape growth control.

Acetoxyacetylaminofluorene↗
PubMed1980

Separation of human bone marrow cells in density gradients of polyvinylpyrrolidone coated silica gel (Percoll).

A simple and highly reproducible method is described for separation and density distribution analysis of human bone marrow cells in continuous density gradients of polyvinylpyrrolidone coated silica gel (Percoll). Colony and cluster forming cells in agar separated from the bulk of cells and peaked at densities of 1.063-1.064 g/ml. The enrichment of clonogenic cells was approximately 10 times and recovery varied between 41-321%. The overall recovery of cells was 80% (60-94%). Density distribution analysis of morphologically identifiable cells demonstrated the progressive increase in density with maturation of cells within the granulocytic series: myeloblasts peaked at 1.0624 g/ml, promyelocytes at 1.0734 g/ml, myelocytes at 1.0776 g/ml, metamyelocytes at 1.0799 g/ml and mature neutrophils at 1.0864 g/ml. The eosinophil had the highest density, 1.0904 g/ml, of all cells analyzed. Monocytes and lymphocytes peaked at 1.0661 and 1.0681 g/ml respectively. The light density shift of clonogenic cells of AML and CML reported by other authors was confirmed.

Blood Cells↗
PubMed1980

Serum ferritin in the elderly.

A two-site immunoradiometric assay for human ferritin has been developed using antibody-coated polystyrene tubes. Serum ferritin was measured in fifty-four men and women aged 73 years. The geometric mean was 166 micrograms/l for thirty-one men and 161 micrograms/l for twenty-two women. One woman was excluded from the statistical calculations. Twenty-eight of the subjects had earlier participated in a study of food consumption by the duplicate portion technique. There was a significant correlation (r = 0.44, P < 0.01) between the food iron intake and the serum ferritin values. A reference material of men and women aged 18-55 years was also analysed. The geometric mean for males was 170 micrograms/l with a 95% confidence range of 46-637 micrograms/l. The female controls were found to have significantly lower values (geometric mean 51 micrograms/l, 95% confidence range 10-260 micrograms/l) than both the older women (P < 0.001) and the male controls (P < 0.001).

Adolescent↗
PubMed1980

Biochemical characterization of a leukemia-associated inhibitor (LAI) suppressing normal granulopoiesis in vitro.

Low-density (less than 1.077 g/ml) marrow or blood cells from patients with acute or chronic leukemia release a high molecular weight substance called "leukemia-associated inhibitor" (LAI) that reduces the fraction of normal marrow CFU-c in S-phase as measured with the 3H-TdR suicide technique. LAI from conditioned media or 3M KCl extracts of subcellular fractions behaved homogeneously on gel chromatography, showing an apparent molecular weight greater than 500,000. However, ion-exchange chromatography and isoelectric focusing indicated considerable charge heterogeneity for LAI molecules. Results from SDS-polyacrylamide gel electrophoresis indicated that the biologic activity resides in a subunit of 150,000-170,000 daltons. The findings of marked affinity for Con-A-Sepharose, marked susceptibility to mild periodate treatment, partial susceptibility to protease digestion, and relative resistance to heating suggest that LAI is a glycoprotein. Data from radiolabeling of cell surface components and sucrose density gradient centrifugation are consistent with LAI being a peripheral cell membrane glycoprotein, which may suppress normal granulopoiesis in leukemia.

Centrifugation, Density Gradient↗
PubMed1979

Hemopoietic precursor cells in human peripheral blood.

Human peripheral blood contains two types of stem cells that differentiate along the granulocytic pathway. They are separable by their ability to form colonies in agar in vitro (CFU-C) and in plasma clots in diffusion chambers in vivo (CFU-DG). Kinetic studies suggest that CFU-DG represents an intermediate between the still hypothetical human pluripotent stem cell and CFU-C.

Animals↗
PubMed1979

Serum and plasma myeloperoxidase, elastase and lactoferrin content in acute myeloid leukaemia.

Myeloperoxidase (MPO) and elastase, restricted to azurophil granules of neutrophils, as well as lactoferrin, restricted to specific granules of neutrophils, were determined in plasma and serum from patients with acute myeloid leukaemia (AML). Highly sensitive radio immuno assays were developed for detection of these proteins. Serum MPO was increased in 12/35 and decreased in 2/35 patients without correlation to WBC or neutrophil counts; these levels may reflect an abnormal production by leukaemic blasts or ineffective granulopoiesis in the bone marrow. Serum elastase was increased in 6/22 patients. Serum lactoferrin was decreased in 12/25 patients without correlation to neutrophil counts probably reflecting abnormal production. Serum elastase and MPO showed a covariation in chronic myeloid leukaemia but not in AML; the latter finding may indicate that the synthesis of these two proteins is not synchronized in AML-cells. Sequential studies of patients with AML demonstrated fluctuations of serum MPO and lactoferrin during remission most likely because of chemotherapeutic pertubation. Although a limited number of patients has been studied it is suggested that serum lactoferrin may be of help for prediction of relapse in AML.

Antineoplastic Agents↗
PubMed1979

Oscillations of marrow culture growth in acute myeloid leukemia during remission induction and remission.

Sequential studies in acute myeloid leukemia of bone marrow cells in agar culture showed striking fluctuations of colony and cluster formation during induction of remission. These oscillations may be initiated by recruitment of resting leukemic and normal cells upon chemotherapeutic perturbation. Striking oscillations of the colony and cluster formation occurred also during remission with or without maintenance therapy, but with a longer periodicity as compared sto the phase of induction of remission. Oscillations of the marrow growth capacity during remission may reflect potential relapses where the outcome depends on proliferative advantages of the normal or leukemic cell clone.

Adult↗
PubMed1978

Inhibitor of hematopoietic cell proliferation derived from a human leukemic cell line.

A continuously growing human myeloid leukemia cell line (K562) produced a potent high-molecular-weight inhibitor of hematopoietic cell proliferation. It was most active against myeloid stem cells (CFU-C) and proliferating T lymphocytes; it was less active against erythroid precursors (CFU-E) and did not inhibit fibroblasts or established lines of epithelioid cells or B lymphocytes. Inhibition of CFU-C was by direct interaction rather than by modulation of production of colony-stimulating activity and probably occurred at restricted points in the cell cycle. Inhibition could, within limits, be reversed by washing the target cells. Production of inhibitors of hematopoiesis is not a general property of established cell lines, and only two have thus far been identified in screening of 30 such lines.

Bone Marrow Cells↗
PubMed1977

Purification of human granulocyte catalase in chronic myeloid leukemia.

Human granulocyte catalase (hydrogen peroxide:hydrogen peroxide oxidoreductase, EC 1.11.1.6) was purified from chronic myeloid leukemia cells. The purification procedure included heat precipitation, ammonium sulphate fractionation, DEAE-Sephadex chromatography, gel chromatography on Sephadex G-200 and isoelectric focusing with an approximate yield of 30% and a 1000-fold purification. The molecular weight of the subunit obtained by sodium dodecyl sulphate electrophoresis was 65 800. So20,w was 11.6 +/- 0.24. The pH-optimum was 6.6-6.7 and the spectrum showed a major peak at 405 nm and shoulders at 500, 540 and 625 nm typical for catalase. The electrophoretic mobility was towards the anode at pH 8.6 and identical to normal granulocyte and erythrocyte catalase. These three species of catalase gave the reaction of identity on immunodiffusion and crossed immunoelectrophoresis. The content of catalase and its activity of isolated granulocytes were approximately identical in normal and chronic myeloid leukemia granulocytes while the specific activity of leukemic catalase was higher than normal. No difference in catalase content was found between mature and immature leukemic granulocytes.

Catalase↗
PubMed1977

Serum myeloperoxidase and lactoferrin in neutropenia.

Radioimmunosorbent assays for determination of serum content of the neutrophil proteins myeloperoxidase and lactoferrin are described. Serial studies were performed in patients with neutropenia. In 2 cases of cyclic neutropenia the myeloperoxidase level showed slight variations within the normal range during the cycle while lactoferrin displayed a clear correlation with neutrophil counts. In 1 case with persistent agranulocytosis myeloperoxidase was normal but lactoferrin was extremely low. During the regeneration phase of drug-induced neutropenia neutrophil counts and serum lactoferrin increased in a parallel fashion. Since serum myeloperoxidase was normal during profounded neutropenia it is suggested to derive primarily from myeloperoxidase-rich granulopoietic precursor cells of the marrow. Serum lactoferrin on the other hand seems to derive from leakage of more granulopoietic cells of blood and marrow. Studies of neutrophil proteins of serum may aid in evaluation of neutropenic patients.

Adolescent↗
PubMed1977

Myeloperoxidase and lactoferrin of blood neutrophils and plasma in chronic granulocytic leukaemia.

Myeloperoxidase, restricted to primary granules, and lactoferrin, restricted to secondary granules, were determined in plasma and neutrophils of peripheral blood in chronic granulocytic leukaemia (CGL). Plasma myeloperoxidase was increased 2-3 times while plasma lactoferrin increased 2-8 times. This discrepancy indicates different modes of release or elimination. A correlation was found between the leucocyte count and plasma myeloperoxidase or lactoferrin. A correlation was also found between cellular and plasma levels of lactoferrin but not for myeloperoxidase indicating the source for plasma lactoferrin to be circulating leucocytes, which may not be the case for plasma myeloperoxidase. Decreased neutrophil lactoferrin was found in 71% of the CGL cases while myeloperoxidase was decreased in 18%. Serial studies on individual CGL subjects showed low cellular lactoferrin during phases with rapidly expanding leucocytosis indicating defective maturation of neutrophils or abnormal release because of prolonged intravascular life-span.

Adult↗
PubMed1977

Pyoderma gangrenosum associated with regional enteritis. Improvement in defective granulocyte function and healing of skin lesions during administration of clofazimine.

A defective uptake of oxygen by peripheral blood granulocytes during phagocytosis, indicating a subnormal phagocytic capacity, has been found in a patient with regional enteritis complicated by pyoderma gangrenosum (PG). During administration of clofazimine and granulocyte function normalized and the skin lesions healed. It is possible that a defective granulocyte function may sometimes be involved in the pathogenesis of PG and that a clofazimine-induced improvement in the function will favour healing of the lesions. The result of treatment in our patient and in other cases recently published indicates that the drug may be worth trying in PG.

Adult↗