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Biomedical subjects

B Simonsson

Publications and source records attributed to B Simonsson.

At least 109 records · Page 6Linked to original sources

Lysis of fresh human B-lymphocyte-derived leukemia cells by interferon-activated natural killer (NK) cells.

Fresh neoplastic B cells from 14 untreated patients with naturally occurring B-cell leukemias were found to be susceptible to lysis by human natural killer (NK) cells. The observed lysis of the fresh, non-cultured, neoplastic B cells was mediated by a population of interferon-augmentable, FcR-positive, non-adherent lymphoid cells, which were also able to kill the "standard" NK target K562. A further finding was the correlation of NK susceptibility with disease activity in 11 patients with chronic lymphocytic (CLL) and one patient with lymphosarcoma cell leukemia (LSCL). Enriched neoplastic B cells from seven untreated patients with non-progressive CLL, whose disease activity was stable throughout the 6 month period of study, exhibited persistent and essentially unchanged NK susceptibility profiles. In contrast, four untreated patients with progressive CLL also had a measurable fraction of NK-susceptible, neoplastic targets, but these cells subsequently disappeared after successful cytoreductive therapy, and later re-emerged when these patients again developed progressive disease. Furthermore, one patient with LSCL was found to have persistent, measurable NK susceptibility in his tumor-enriched fraction after unsuccessful cytoreductive therapy. An additional finding in the peripheral blood of patients with chronic B-cell leukemias was the presence of significantly lower NK effector-cell activity against K562 as compared to normal donor peripheral blood lymphocytes (PBLs). The implications of these findings are discussed.

B-Lymphocytes↗

Prednimustine and vincristine compared with cytosine arabinoside and thioguanine for treatment of elderly patients with acute nonlymphoblastic leukemia.

Sixty-seven patients with acute nonlymphoblastic leukemia (ANLL) and above the age of 60 years were randomly allocated to treatment with either prednimustine + vincristine or cycles with cytosine arabinoside and thioguanine. Of the 67 patients, 13 (19%) entered a complete remission and four a partial remission. Of 33 patients randomized to prednimustine and vincristine (15 adequately treated), three entered a complete remission and one a partial remission. Four further patients went into complete remission after a switch to other treatment modalities. Of 34 patients randomized to cycles of ARA-C and thioguanine (22 adequately treated), four entered a complete remission and three a partial remission with the correct program. One patient entered a remission with intermittent cytosine arabinoside + thioguanine (wrong program) and one further patient entered a complete remission after a switch to prednimustine and vincristine. Prednimustine + vincristine did not appear to be superior to treatment with cytosine arabinoside thioguanine cycles for elderly patients with ANLL.

Acute Disease↗

Comparison of daunorubicin and daunorubicin-DNA complex in the treatment of acute nonlymphoblastic leukemia.

Sixty consecutive patients, 15-60 years old, with ANLL were divided randomly into three groups for induction treatment with one of the following regimens: R1, daunorubicin (DNR) 1.5 mg/kg on day 1 + ARA-C 2 mg/kg body weight on days 1-5; R2, DNR 1.5 mg/kg on days 1 and 2 + ARA-C 2 mg/kg on days 4-8; R3, DNR-DNA complex 1.5 mg/kg on days 1 and 2 + ARA-C 2 mg/kg on days 4-8. Maintenance treatment consisted of monthly courses of DNR 1.5 mg/kg (R1, R2) or DNR-DNA 1.5 mg/kg (R3) combined with ARA-C 1 mg/kg on days 1-5, alternating with thioguanine 2 mg/kg PO on days 1-5 combined with ARA-C 1 mg/kg IV on days 1-5. Fourteen patients of 20 went into complete remission with R1, 13 or 18 with R2, and 15 of 22 with R3. The overall remission frequency was 70% and there was no significant difference between the different groups. The median time in first remission and the median survival time were 300 and 510 days, respectively, with R1; 335 and 495 days with R2; and 295 and 677 days with R3. There was no statistically significant difference between the groups treated according to the different regimens concerning the time in first remission. Survival was slightly better with R3 than with R1. Treatment with the DNR-DNA complex caused less pronounced thrombocytopenia and fewer 'minor' cardiac abnormalities than treatment with free DNR in the same dosage schedule.

Acute Disease↗

Serum ferritin in the regulation of iron therapy in blood donors.

12 regular blood donors were selected on the basis of subnormal serum ferritin levels as a criterion for iron deficiency. It was found that all had high transferrin levels but only 5 had subnormal serum iron or transferrin saturation. The donors were given oral iron therapy in a dose of 2,800 mg between each phlebotomy, and the donation interval was standardized to 8 weeks. Test samples were collected every 4th week. After an initial rise in ferritin during the first 2 months, 6 of the donors again had subnormal serum ferritin levels, and the iron dose was therefore doubled after 32 weeks. Following this, all subjects taking the higher dose had normal ferritin values and stainable marrow iron was found at the end of the study, after 92 weeks. 3 subjects did not take the higher dose, had no raised serum ferritin level or stainable hemosiderin. It is concluded that serum ferritin estimation can be used to monitor the therapy in blood donors so that a satisfactory amount of iron is stored.

Blood Donors↗

3H-thymidine uptake in chronic lymphocytic leukaemia cells.

The clinical variability of chronic lymphocytic leukaemia (CLL) is well known. The short and long term prognosis is usually difficult to predict in the individual case. In the present work the proliferative activity in peripheral CLL cells of 38 patients was analysed by 3H-thymidine uptake and a proliferative index (PI = labelling index x white blood cell count/1 x 10(-9)) was calculated. A strong correlation between PI and clinical disease activity was found. Thus 22 out of 23 patients with non-progressive disease had normal values (PI less than 10). 8 out of 8 cases with PI greater than 20 had a clear disease progression in all blood variables. The PI interval 10--20 comprised both patients with progressive and patients with non-progressive disease. Variations in PI correlated well to variations in clinical disease activity in 8 patients examined at intervals during long term treatment. The results indicate that determination of PI might be used as therapy guide since it was normalized during successful treatment.

Absorption↗

Beta 2-microglobulin in chronic lymphocytic leukaemia.

The serum level of beta 2-microglobulin (S-beta 2 m), a cell membrane protein associated with HLA-antigens, was quantitated in a series of 23 consecutive patients with chronic lymphocytic leukaemia (CLL). Markedly elevated values of S-beta 2 m (greater than 4.5 mg/1) were found in 10 patients, while only 3 patients had normal values (less than 3.0 mg/1). High serum values correlated with a large tumour mass, as estimated by Rai's clinical staging and by the total peripheral lymphocyte count. Blood lymphocyte proliferative activity, which has been suggested as reflecting disease activity in CLL, was measured by 3H-thymidine uptake in cells in vitro. The 3H-thymidine uptake was high in 3 patients all of whom were among the 5 patients with the highest S-beta 2m-values. S-beta 2m-determinations seem to be of definite interest in the study of patients with CLL although long term studies will be necessary for evaluation of the practical clinical value.

Aged↗

Treatment of acute nonlymphoblastic leukemia in adults with daunorubicin-DNA complex: a preliminary report.

Forty-four adult patients under 60 years of age with acute nonlymphoblastic leukemia were randomized for induction treatment with one of the following three regimens: R 1 = courses of daunorubicin on day 1 + ARA-C on days 1--5; R 2 = courses of daunorubicin on days 1 and 2 + ARA-C on days 4--8; R 3 = courses of daunorubicin-DNA complex on days 1--2 + ARA-C on days 4--8. Out of 14 patients, 9 went into remission on R 1, 6 out of 14 on R 2, and 8 out of 16 on R 3. The preliminary results suggest that daunorubicin-DNA complex has the same efficacy for inducing remission as daunorubicin alone, if the same time intervals and dosages are used.

Acute Disease↗

Effects of prednisolone in 6 cases of glucocorticoid receptor-positive CLL.

The effect of treatment with prednisolone on clinical and laboratory variables was studied in 6 patients with chronic lymphocytic leukaemia (CLL). The laboratory variables analyzed on the leukaemic cells were surface immunoglobulin (S-Ig), sheep red blood cell receptors (SRBC), proliferative activity (PI) and glucocorticoid receptor (GR). In all cases the CLL was of B-cell type and the leukaemic cells contained a significant amount of GR. 4 out of 6 patients had a progressive disease with increased PI. On treatment they went into clinical remission, which was paralleled by a reduction in the leukaemic B-cell number and in PI. The amount of GR was unaffected. In 2 patients with nonprogressive disease, prednisolone produced no clearcut effect on clinical or laboratory variables.

Complement System Proteins↗

Biochemical characteristics of chronic lymphocytic leukaemia. Glucocorticoid receptors, B and T lymphocyte surface markers, concanavalin A-induced agglutination and thymidine incorporation.

Chronic lymphocytic leukaemia (CLL) has a variable clinical course and there is a great need of new prognostic laboratory parameters in this disease. 24 CLL patients were subjected to routine haematological and clinical investigation. The leukaemic cells were analyzed for surface immunoglobulins, complement and sheep red blood cell receptors, Concanavalin A-induced agglutination, cytoplasmic glucocorticoid receptor and for proliferative activity by measurement of tritiated thymidine incorporation. The surface markers studied indicated that all cases were of B-cell origin. Only 5 of 23 patients studied had normal serum immunoglobulin levels. These cases showed a nonprogressive disease. 8 patients had increased infection tendency, all of whom had subnormal IgG levels; 4 of them also had subnormal IgA and IgM and 2 had subnormal IgA levels. 5 out of 6 patients with progressive disease and 3 of 11 with nonprogressive disease had an increased proliferative index, indicating a correlation between this parameter and disease progression. ConA agglutinability was not correlated to disease activity. Cells from 17 of 22 patients showed measurable amounts of glucocorticoid receptor. The 5 patients lacking this receptor had inactive disease.

Aged↗

Ferastral treatment of three healthy phlebotomized males.

Iron deficiency anaemia was produced by repeated phlebotomies in three healthy males. The storage iron was estimated as 666, 522 and 750 mg. After treatment with 1 000 mg of Ferastral the blood haemoglobin concentration rose at an average daily rate of 0.1 g/100 ml/day. Ninety per cent of the injected iron could be accounted for, and the utilization was estimated to about 70-80%. Side effects comprised pain and discolouration at the injection site.

Adult↗

Serum ferritin and erythrocyte 2,3-DPG during quantitated phlebotomy and iron treatment.

Serum ferritin and erythrocyte 2,3-DPG levels were followed in 3 healthy males who were phlebotomized to iron depletion and a moderate anaemia. In 2 of the subjects, the expected rise in DPG levels was seen but not in the third, in spite of a Hb concentration of 95 g/1. Serum ferritin levels were found to reflect changes in iron stores, and subnormal serum ferritin indicated depleted iron stores. However, there was no correlation between pre-phlebotomy ferritin levels and calculated iron stores. The conclusion is that no fixed ratio can be established between serum ferritin and iron stores. A single ferritin value within the normal range does not tell how large iron stores a person has. Changes in an individual's iron stores can, however, be detected by repeated ferritin estimations.

Adult↗

Evidence for glucocorticoid receptor in human leukocytes.

The glucocorticoid uptake in vitro by human periferal leukocytes was studied. The uptake showed 2 main components, one saturable and one non-saturable. The saturable component was compared with the uptake by the specific glucocorticoid receptor in rabbit granulocytes. The similarities with the rabbit receptor in structural specificity, time course of uptake at 37 degrees C, sensitivity to metabolic inhibition by PCMS and the physiological concentration for half saturation indicate that the saturable component corresponds to a specific glucocorticoid receptor. Cells from chronic lymphatic leukemia and chronic myeloic leukemia were also studied. Only the former had a saturable glucocorticoid uptake.

Adult↗