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Biomedical subjects

B Simonsson

Publications and source records attributed to B Simonsson.

At least 91 records · Page 5Linked to original sources

Serum deoxythymidine kinase correlates with peripheral lymphocyte thymidine uptake in chronic lymphocytic leukemia.

The serum thymidine kinase (S-TK) and proliferative activity of the leukemic cells were determined in 27 untreated patients with chronic lymphocytic leukemia (CLL). A significant positive correlation between S-TK and proliferation expressed as a proliferative index (PI) was found (r = 0.70, p less than 0.001). Additionally, PI (r = 0.59, p less than 0.01) and S-TK (r = 0.47, p less than 0.05) correlated to peripheral blood lymphocyte count. When different variables and combinations of variables were studied in order to define their capacity for discriminating between progressive and indolent CLL, S-TK activity and PI proved to be powerful indications. In longitudinal studies, both S-TK and PI paralleled disease activity. A model where a combination of S-TK and PI gives information of the degree of localized disease is proposed.

Adult↗

Myeloid regeneration after bone-marrow transplantation monitored by serum measurements of myeloperoxidase, lysozyme and lactoferrin.

Bone-marrow regeneration after chemo- and radiotherapy-induced aplasia can be monitored by serum levels of myeloperoxidase (MPO), lysozyme (LYS) and lactoferrin (LF). In 10 patients with leukemia, serum measurements were performed before and after bone-marrow transplantation. Bone-marrow regeneration was suggested by increments in serum MPO and LYS 5 and 4 days prior to the increase in mononuclear cells (Mono) and 10 and 9 d before the increase in polymorphonuclear leukocytes (PMN) in the peripheral blood. LF started to rise 4.5 d before detectable circulating PMNs. 2 patients with early relapses of leukemia post transplantation are shown to display atypical patterns of serum MPO and LYS. We conclude that serum measurements of MPO, LYS and LF may be used as early and sensitive means to monitor bone-marrow activity during hematological regeneration. However, the findings also strongly support the earlier proposal that MPO alone may be used to reflect myeloid activity in the bone-marrow in general.

Adolescent↗

Pretreatment serum beta 2-microglobulin in multiple myeloma.

Serum beta 2-microglobuline (S-beta 2m) was evaluated in 121 untreated patients with multiple myeloma. Values greater than 3 mg/l were found in 82% of the patients. Mean S-beta 2m values of the total group of patients correlated with clinical stage. However, there was no correlation if values were corrected for S-creatinine. Seventy-nine patients had normal (less than or equal to 106 mumol/l) and 52 patients abnormal S-creatinine. Patients with S-beta 2m values below 7 X 6 mg/l had an estimated median survival of 44 months compared to 12 months for patients with levels above 7 X 6 mg/l. If S-beta 2m values in patients with normal S-creatinine were combined with values corrected for S-creatinine from patients with elevated S-creatinine a beta 2m cut off level of 6 X 6 mg/l gave a median probable survival of 43 months compared to 14 months. We conclude that pretreatment S-beta 2 microglobulin is a useful marker for predicting survival in multiple myeloma. The problem of the relationship between S-beta 2m and S-creatinine is discussed.

Adult↗

Phorbol ester-induced production of beta-2-microglobulin in B-CLL cells: relation to IgM secretory response and disease activity.

Earlier studies have indicated that serum beta 2m levels correlate with the disease activity, estimated tumour cell mass and prognosis of CLL. We have therefore analysed the spontaneous and phorbol ester (TPA)-induced capacity of CLL cells to produce beta 2m in vitro in relation to disease activity. Cell cultures (greater than 90% B cells) from 15 patients with active disease contained significantly higher (P less than 0.001) levels of beta 2m (0.22 +/- 0.09 mg/l) than cultures from 17 patients with inactive CLL (0.08 +/- 0.06). When TPA-induced CLL cell cultures were compared, this difference was even more striking (0.48 +/- 0.18 versus 0.13 +/- 0.09). The capacity of TPA-treated B-CLL cells to export beta 2m was positively correlated with their capacity to secrete monoclonal IgM (r = 0.73; P less than 0.001). Cell depletion experiments showed that the beta 2m export by B-CLL cells is enhanced by accessory T cells. Four individual CLL patients were followed for 14 months and repeatedly investigated for signs and symptoms of active disease, and the CLL cells were tested for in vitro production of beta 2m. Fluctuations in the clinical activity of the leukaemia were paralleled by similar switches in CLL cell production of beta 2m.

Adolescent↗

Production of beta 2-microglobulin by chronic lymphocytic leukaemia cells in vitro.

The in vitro production of beta 2-microglobulin (beta 2m) by leukaemic cells was studied in 22 patients with chronic B-lymphocytic leukaemia (CLL). In addition, the concentration of beta 2m in serum (S-beta 2m) was determined and expressed as percent of the upper normal limit, after a correction for elevated S-Creatinine values. Patients with progressive disease usually had CLL cells with a high rate of in vitro synthesis and an increased S-beta 2m. This was not found in patients with non-progressive disease. The in vitro synthesis of beta 2m X the lymphocyte count correlated with S-beta 2m in the total material (r = 0.65). The increased S-beta 2m frequently observed in CLL may therefore originate from the tumour cells. Hence, S-beta 2m is promising as a clinically useful tumour cell-associated marker in CLL.

Aged↗

Evaluation of serum deoxythymidine kinase as a marker in multiple myeloma.

A recently developed deoxythymidine kinase assay utilizing 125I-iododeoxyuridine as substrate was used in an investigation of sera from 122 untreated patients with multiple myeloma. Most patients had slightly elevated or normal serum deoxythymidine kinase activity (S-TK), although in some patients values increased by more than forty-fold were found. S-TK correlated with the haemoglobin level but did not correlate with sex, age, erythrocyte sedimentation rate, nor with the serum concentrations of creatinine, beta 2-micro-globulin, Ca or M-component. The distribution of S-TK values in IgG, IgA and pure Bence-Jones myeloma did not differ significantly. Patients with IgG and IgA myeloma excreting light-chain immunoglobulin in the urine had significantly higher S-TK than non-excreters. There was a significant correlation between S-TK values and tumour cell mass as determined by clinical staging. A high pretreatment S-TK (greater than 5.1 units) also distinguished a group of patients with a significantly shorter survival time. Patients with no response to initial therapy had significantly higher S-TK values than those who did respond. In longitudinal studies of 11 patients, S-TK was found to increase when the disease became more aggressive. The possibility of diagnosing disease progression at an early stage by an elevation of S-TK is discussed.

Adult↗

Alpha interferon treatment of patients with hairy-cell leukaemia.

We have treated 10 patients with hairy-cell, or hairy-cell-like leukaemia, for more than 6 months, with alpha interferon 3 X 10(6) IV/day I.M. or subcutaneously. All patients were severely pancytopenic before treatment. 7 patients had a typical hairy-cell leukaemia, whereas 3 lacked hairy cells but had the characteristic bone-marrow infiltration. The peripheral blood counts improved in all patients during treatment and the lymphoid infiltration of the bone-marrow was shown to decrease. 1 patient obtained complete remission, 6 partial remission and 3 had a minor response. It is concluded that alpha interferon is effective in the treatment of patients suffering from hairy-cell leukaemia.

Aged↗

The chemokinetic inhibitory factor (CIF) in serum of CLL patients: correlation with infection propensity and disease activity.

We have recently described the partial purification and characterization of a neutrophil migration inhibitory activity present in serum from patients with chronic lymphocytic leukaemia (CLL). This new lymphokine, the chemokinetic inhibitory factor (CIF), is produced by B-CLL cells. It is a heat-labile glycoprotein of an approximate molecular weight (m. w.) of 30000. In this extended investigation 64/89 CLL-patients had CIF in their serum. CLL serum diluted to a concentration of 0.02% gave significantly decreased chemokinetic activity, suggesting that CIF is potent at very low concentrations. 31/89 patients had increased infection propensity. Significantly more patients with CIF in serum had infections compared to the group with normal susceptibility to infections. The combination of low Ig levels and CIF in serum discriminated even better between the infection-prone and non-infection-prone patients. CIF in serum was not correlated to tumour cell mass - estimated by Rai clinical staging - tumour progression or deoxythymidine kinase, S-TK, an enzyme that may reflect proliferating cells. The existence of this new lymphokine in serum seems to contribute to the increased susceptibility to infections seen in CLL patients.

Adult↗

Serum deoxythymidine kinase gives prognostic information in chronic lymphocytic leukemia.

A recently developed deoxythymidine kinase assay, utilizing iodine-125-iodo-deoxyuridine as substrate and capable of detecting enzyme activity in serum from healthy humans, was used in an investigation of sera from 55 untreated patients with chronic lymphocytic leukemia (CLL). When confined to the study, the patients were classified as having progressive or indolent disease and according to Rai stage. The results showed a significant correlation between serum deoxythymidine kinase activity (S-TK) and disease status, i.e., higher values were found in patients with progressive disease, compared to those with indolent disease. S-TK also correlated with Rai stage. S-TK values of more than 40 times the normal value were found in some patients. All patients with S-TK greater than 8.4 units had a disease that was or became progressive during the observation period. Within the patient group with indolent disease two groups that differed with regard to prognosis could be distinguished according to their initial S-TK values. In longitudinal studies of 18 patients with indolent disease, S-TK was found to exceed 8.4 units only on one occasion during an observation period of up to 68 months. In patients with indolent disease, a transition to progressive disease was parallelled by an increase in S-TK. Studies of S-TK levels in 18 patients receiving treatment showed that S-TK decreased during successful therapy. S-TK was also found to increase when the disease was reactivated. From these results it is concluded that S-TK could be used as a prognostic marker for the individual CLL patient. Furthermore, S-TK seems to be useful for longitudinal follow-up studies of disease status, both in indolent disease and in progressive disease during treatment.

Adult↗

Effect of food on pharmacokinetics of chlorambucil and its main metabolite, phenylacetic acid mustard.

The influence of food intake on the pharmacokinetics of chlorambucil (C) and its cytotoxic metabolite, phenylacetic acid mustard (PAM), has been studied in man after oral doses of chlorambucil. The administration of chlorambucil with food resulted in slower absorption than when fasting. However, the area under the plasma concentration-time curve (AUC) was unaffected. The mean ratio AUCPAM/AUCC was 2.8 (range 1.4-7.1) under fasting and 3.3 (range 1.3-7.4) under nonfasting conditions. The metabolite very probably plays an important role in the cytotoxic effects observed after administration of C, since calculations show that a major fraction of the metabolite is eliminated by alkylation reactions.

Adult↗

Serum beta 2-microglobulin in malignant lymphoma.

Serum beta 2-microglobulin (S-beta 2m) was measured at diagnosis in 189 patients with malignant lymphoma, all with a normal serum creatinine clearance. The diagnosis was non-Hodgkin's lymphoma (NHL) in 149 patients and Hodgkin's disease (HD) in 40. Among the NHL group, S-beta 2m was raised (greater than 3.0 mg/l) in 15% of patients with Stage I and II and in 65% of those with Stage III and IV. The corresponding frequencies for HD were 11% and 83% respectively. In NHL, a high pretreatment level of S-beta 2m was found to be a poor prognostic sign in all stages. Patients in Stage I and II with an elevated pretreatment level of S-beta 2m had a higher relapse rate than those with normal S-beta 2m. In Stage III and IV patients with initial levels greater than 3.5 mg/l, the survival was significantly shorter than in those with initial values of less than 3.5 mg/l. A lower mean S-beta 2m value was found in Stage III and IV patients who achieved complete remission than in those who did not. Serial determinations of S-beta 2m in 23 patients with NHL showed that increased pretreatment levels became normal when remission was achieved and increased again in relapse. Thus the S-beta 2m provides valuable prognostic information in this group of patients.

Adolescent↗

Density separation of chronic lymphocytic leukemia cells: low-density non-T cells are efficient stimulator cells in allogeneic and autologous mixed leukocyte reaction.

Unseparated mononuclear cells and E rosette-depleted non-T cells from a majority of patients with chronic lymphocytic leukemia (CLL) were found to be weak stimulators in the allogeneic mixed-leukocyte reaction (MLR). However, a minor population (1-5%) of highly active stimulator cells could be isolated from all patients studied by buoyant density centrifugation using discontinuous gradients of Percoll. The same low-density non-T-cell fraction also stimulated autologous T-cell proliferation in the autologous mixed-leukocyte reaction (AMLR). In contrast, Percoll-separated high-density non-T cells, including the leukemic B-cell pool, were completely inactive as stimulators in AMLR. These results suggest that the presence of efficient stimulator cells among CLL mononuclear cells may be masked by the large number of nonstimulating leukemic B cells.

Cell Separation↗

Intermittent high-dose melphalan/prednisone vs continuous low-dose melphalan treatment in multiple myeloma.

Patients with newly diagnosed multiple myeloma were randomly allotted to an intermittent high-dose melphalan/prednisone (MP) treatment (120 patients) or a continuous low-dose melphalan (M) regimen (99 patients). The median observation time was 59 months (range 33-84). Response to therapy was obtained in 45% of the MP group and 31% of the M group (P less than 0.05). No significant difference in response with regard to clinical stage was noted. Median survival was 36 months in the MP group and 29 months in the M group. Survival was longer in stage I and II myeloma than in the stage III cases, at least in the MP group. The median and 5-yr survival rates in stages I and II were significantly better in the MP than in the M group. Response to therapy was associated with length of survival, median survival being 62 months in responding patients and 20 months in non-responders. The MP and M groups did not differ in this respect.

Adult↗

The use of serum deoxythymidine kinase as a prognostic marker, and in the monitoring of patients with non-Hodgkin's lymphoma.

A recently developed enzyme assay, utilizing [125I]-iododeoxyuridine as substrate, and capable of detecting normal levels of serum deoxythymidine kinase (s-dTk), was used in an investigation of sera from 155 untreated patients with non-Hodgkin's lymphoma (NHL). The patients were classified at the discovery of disease, both according to spread (stages I-IV according to the Ann Arbor classification) and to tumour histology (the Kiel classification). The results showed a significant correlation between s-dTk level and the extent of disease, as well as to the malignancy; i.e. the more advanced the disease or the more aggressive the tumour, the higher the s-dTk values. Greater than 100-fold increases in s-dTk levels were found in some patients compared to those reported for healthy individuals. A high pretreatment level of s-dTk for patients in stages III-IV correlated with a poor prognosis for the patient in terms of survival. This was consistent even when only patients in stages III-IV with "high-grade" malignant lymphomas were included in the analysis. Longitudinal studies of s-dTk levels in 19 NHL patients showed that s-dTk increases with progression of the disease, decreases during successful therapy, and finally increases during relapse. It is concluded that s-dTk could be used both as a prognostic marker and to monitor the effect of therapy in NHL patients.

Adolescent↗

Surface glycoprotein patterns of B type chronic lymphocytic leukaemia cells correlate with the clinical activity of the disease.

The surface glycoprotein patterns of leukaemic B lymphocytes from 20 patients with clinically progressive or non-progressive chronic lymphocytic leukaemia (CLL) were investigated. Cells were labelled by the neuraminidase-galactose oxidase-tritiated sodium borohydride technique and the radioactive proteins were separated by polyacrylamide slab gel electrophoresis and visualized by fluorography. A total of 13 to 16 bands were detected. A common surface glycoprotein pattern for CLL cells was seen in all patients consisting of 7 proteins with the apparent molecular weights of 210, 200, 185, 150, 135, 110 and 90 kilodaltons, respectively. Interesting differences were, however, observed as cells from patients with progressive CLL in general lacked the glycoproteins 120, 72 and 67 K, which were found on cells from inactive CLL. The possible biological and clinical significance of these findings is discussed.

Aged↗

Glucocorticoid receptors, clinical characteristics, and implications for prognosis in chronic lymphocytic leukemia.

The cytoplasmic glucocorticoid-receptor (GR) content was analyzed in peripheral leukocytes from 52 nonselected patients with chronic lymphocytic leukemia (CLL). Forty-six patients had measurable GR levels. Six patients lacking measurable GR and seven of eight patients with a low GR content had inactive disease. However, there was no significant difference in average GR content between patients with progressive or nonprogressive disease. Twelve GR-positive patients were treated with prednisolone as the sole medication. Seven patients responded, some in several treatment sessions. There was no correlation between GR-content and clinical response. Thus, in our experience, cytoplasmic GR measurement has only limited predictive value.

Humans↗