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T Olofsson

Publications and source records attributed to T Olofsson.

87 records · Page 5Linked to original sources

Granulopoiesis in infantile genetic agranulocytosis. In vitro cloning of marrow cells in agar culture.

A 3-year-old boy and a 2-year-old girl with infantile genetic agranulocytosis have been studied by in vitro cloning of bone marrow cells in agar culture. The patients display a normal concentration of colony forming cells and the morphological maturation is identical with that of control marrow cultured in vitro. The marrow cells of the patients show some degree of auto-stimulation indicating that endogenous production of colony stimulating factor is operating. As an inverse relationship is expected between the peripheral neutrophil count and the percentage of marrow colony forming cells in S-phase a high percentage was expected. On the contrary, we find that the percentage of colony forming cells in S-phase is extremely low indicating a genetic unresponsiveness of granulopoietic precursor cells to feed back regulation in infantile genetic agranulocytosis.

Agranulocytosis↗

Granulopoiesis in chronic myeloid leukemia. II. serial cloning of blood and bone marrow cells in agar culture.

Colony-forming cells (CFC) and CFC in S-phase were assayed in chronic myeloid leukemia (CML). A correlation was found between leukocyte counts and CFC of blood, suggesting that the leukocytosis of CML depended on expansion of the committed granulopoietic stem cell compartment. Serial studies performed in four cases demonstrated a decrease of the CFC in S-phase during early stages of developing leukocytosis, which was consistent with the operation of growth control mechanisms. During later stages, serial studies revealed that sudden increments of CFC S-phase coincided with rapidly growing leukocytosis, which was consistent with leukemic cell populations escaping growth control. H-thymidine labeling indices for differentiated precursor cells showed slight variations not coinciding with variations of the CFC S-phase fraction. Cyclic oscillations of the white cell count were observed in one case. The white cell count and the fraction of CFC in S-phase displayed a direct relationship, indicating that the occurence of cycles was not likely to be due to a negative feedback mechanism elaborated by mature granulocytes. In another case, marked cycling of the CFC S-phase fraction was found without distinct oscillations of the white cell count. The present work has emphasized the necessity for serial assays of parameters of cell kinetics in vitro in CML since changing relationships were found between stem cell and differentiated cell kinetics during different phases of the disease.

Adult↗

Granulocyte function in chronic granulocytic leukemia. II. Bactericidal capacity, phagocytic rate, oxygen consumption, and granule protein composition in isolated granulocytes.

The initial rate of phagocytosis, oxygen consumption rate during phagocytosis, bactericidal capacity against Escherichia coli, and the granule protein composition of isolated mature-appearing granulocytes were studied in 23 patients with chronic granulocytic leukemia (CGL) with the simultaneous use of normal controls. The initial rate of phagocytosis was decreased (p less than 0.05) in the CGL patient group, as were oxygen consumption rate (p less than 0.001) and bactericidal capacity (p less than 0.001). Kinetic analysis of the ingestion rate showed CGL granulocytes to have the same capacity to bind the particles as normal granulocytes. Both specific and primary granule protein deficiencies were shown for CGL granulocytes, and these deficiencies were more pronounced at or near blast cell transformation. Analysis of all different granulocyte function parameters showed an inverse correlation to white blood cell counts (p less than 0.01) and to the percentage of immature granulocytes in peripheral blood (p less than 0.001). The leukocytosis doubling time was progressively shortened during the chronic course of the disease. A correlation was found between granulocyte function parameters and leukocytosis doubling time (p less than 0.001), indicating that granulocyte function was progressively deteriorating during chronic phase CGL, and may be an expression of increasing disturbance of the differentiation process.

Blood Bactericidal Activity↗

Granulocyte function in chronic granulocytic leukaemia. I. Bactericidal and metabolic capabilities during phagocytosis in isolated granulocytes.

The ingestion, bactericidal activity and metabolism of isolated mature neutrophil leucocytes during phagocytosis was studied in 17 patients with chronic granulocytic leukaemia (CGL) with the simultaneous use of normal controls. Seven patients had received no treatment and the others had been treated previously with Busulphan. The phagocytic indices for killed yeast cells did not differ from those of the controls. A diminished bactericidal activity against E. coli was found in nine CGL cases. The bactericidal capacity closely correlated with the degree of leucocytosis since patients with a WBC count of 90 000/mul or higher with one exception showed decreased bactericidal activities while patients with WBC counts below 90 000/mul with two exceptions showed normal bactericidal activities. The [I-14C]-glucose oxidation during phagocytosis was increased in four patients and decreased in three patients. Some correlation was found between abnormally high or low [I-14C]glucose oxidation and diminished bactericidal activity. The intracellular iodination reaction during phagocytosis was decreased in 10 cases while the extracellular iodination was increased in six cases and decreased in one case. The data for granulocyte iodination did not correlate with WBC count, bactericidal capacity or [I-14C]glucose oxidation. The time course for the bactericidal activity and granulocyte iodination seemed to deviate from the controls indicating a slow initial ingestion and/or degranulation phase. The CGL granulocyte content of myeloperoxidase was normal or increased, the lysozyme content was decreased in half of the cases while the amount of antibacterial cationic proteins was increased, normal or low. The present findings indicate a variety of abnormalities in the mature CGL granulocyte, which are not closely interrelated.

Blood Bactericidal Activity↗

Cell production and cell function in human cyclic neutropenia.

In vitro studies have been done on haematopoietic cells from a patient with cyclic neutropenia characterized by severe depression of blood neutrophil levels every 21 days. Serial blood counts reveal periodic fluctuations in neutrophils, monocytes and reticulocytes. Agar culture of marrow cells shows normal concentration of colony forming cells. The percentage of colony forming cells in S phase is highly increased during profound neutropenia and normal during the recovery phase relating the granulocyte production to the peripheral neutrophil level. Studies of ingestion rate, bactericidal activity, lactate production and glucose oxidation during phagocytosis in isolated granulocytes show normal results. Also the ingestion rate in isolated monocytes is normal. Serial karyotype analyses of marrow cells during the neutrophil cycle display a normal pattern. Serum myeloperoxidase levels vary inversely with the peripheral neutrophil count indicating increased granulopoietic activity during profound neutropenia, which might be associated with non effective granulopoiesis during profound neutropenia, leading to a lack of granulocyte reserves in the marrow.

Adolescent↗

Relationship between myeloblasts and cluster-forming cells in acute non-lymphocytic leukemia.

The relationship between myeloblast-like cells and cluster-forming cells detected by growth in agar has been studied in 22 untreated patients with acute non-lymphocytic leukemia by means of comparing data for 3H-TdR labelling of myeloblast-like cells and 3H-TdR suiciding of cluster-forming cells. The fraction of myeloblast-like cells in S-phase was significantly smaller (13.1 +/- 8.7 per cent) than the fraction of cluster-forming cells in S-phase (35.5 +/- 15.3 per cent). In 2/22 patients approximately half of the myeloblast-like cells in DNA-synthesis were calculated to produce clusters in agar which may suggest similarity for cell cycle active myeloblast-like cells and cluster-forming cells. The other patients showed decreased plating efficiency for myeloblast-like cells in S-phase indicating non-identity or modification of the growth pattern due to environmental factors and variations in death rate during culture. Sequential studies in three patients indicated a changing relationship between myeloblast-like cells and cluster-forming cells suggesting non-identity or differences in growth regulation during the course of the disease.

Acute Disease↗