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Biomedical subjects

L Skoog

Publications and source records attributed to L Skoog.

At least 145 records · Page 8Linked to original sources
PubMed1985

Determination of glucocorticoid receptors in leukemic myeloblasts by isoelectric focusing in polyacrylamide gel.

We investigated the optimal conditions for measuring glucocorticoid receptor in blast cells from patients with acute nonlymphocytic leukemia. Cytosol receptor measured with isoelectric focusing was saturated after 60 min of incubation at 0 degrees C with 100 nM of either dexamethasone or triamcinolone. Saturation was achieved when cytosol from at least 7 X 10(6) cells was used for incubation. Trypsin treatment of the cytosol resulted in a sharpened peak of receptor focusing at pH 5.6 with no loss of receptor-bound radioactivity. The two physical forms of glucocorticoid receptor were isolated with DEAE cellulose chromatography. They were both found to focus at pH 5.6 during isoelectric focusing.

Acute Disease↗
PubMed1985

Hypocholesterolemia in cancer patients may be caused by elevated LDL receptor activities in malignant cells.

Several epidemiological studies indicate an inverse relation between plasma cholesterol and the occurrence of cancer. Since we in previous studies have found that certain malignant cell types have an elevated LDL receptor activity, the aim of the present study was to further explore the possibility that an elevated LDL consumption by tumor cells causes hypocholesterolemia. The plasma cholesterol concentrations in patients with acute leukemia were inversely correlated with the rate of receptor-mediated degradation of 125I-LDL by the leukemic cells. During chemotherapy, the total plasma and the LDL cholesterol levels increased concomitantly with the reduction in the leukemic cell count in a patient whose leukemic cells exhibited a high rate at receptor-mediated degradation of 125I-LDL. In certain patients with inoperable urinary bladder carcinoma, the plasma cholesterol concentration fell as the disease progressed. Studies in breast cancer patients indicate that the number of LDL receptors in the tumor tissue may have prognostic significance. The results are in agreement with the hypothesis that an elevated LDL receptor activity in malignant cells may lead to hypocholesterolemia.

Blood Donors↗
PubMed1985

Receptors for retinoic acid and retinol in human mammary carcinomas.

The cellular content of receptors for retinol (CRBP) and retinoic acid (CRABP) was measured in 148 human mammary carcinomas. High levels of CRABP were found in lobular carcinomas while those of the papillary subgroup had low levels of the receptor. Intermediate values for CRABP were observed for ductal, colloid and medullar carcinomas. The cellular levels of CRBP were high in ductal carcinomas and low in papillar carcinomas. A positive correlation was observed between the receptor for estradiol and CRABP. However, no significant correlation was found between the tumor cell DNA pattern and the content of CRABP and CRBP respectively. Recurrence of disease could be predicted by the nodal status and the level of estradiol receptor while the DNA pattern and the content of receptors for retinoic acid and retinol failed.

Adenocarcinoma, Mucinous↗
PubMed1985

Influence of genotype and the organ of origin on the subtype of T-cell in Moloney lymphomas induced by transfer of preleukemic cells from athymic and thymus-bearing mice.

Thymus, spleen, and bone marrow of 1-month-old neonatally Moloney murine leukemia virus-inoculated mice have been transferred to 400-R-irradiated syngeneic recipients of the opposite sex. The donor or recipient origin of T-cell lymphomas arising in the host animal was identified by the sex chromosome marker. Spleen and bone marrow of athymic BALB-nu/nu mice contain cells with the potential to develop into T-cell lymphomas upon transfer to thymus-bearing BALB/c recipients. Such lymphomas arise from at least two subsets of T-cells, one terminal deoxynucleotidyl transferase (TdT) positive and the other 20 alpha-hydroxysteroid dehydrogenase positive. The enzyme-negative precursor T-cells from the BALB-nu/nu spleen and bone marrow can thus mature to enzyme-positive cells and give rise to lymphoma in the thymus-bearing recipient. Preleukemic spleen and bone marrow, but not thymus, from CBA and BALB/c mice regularly contained cells with the potential to develop lymphoma. The subset of T-cell involved was influenced by the genotype since lymphomas arising after the transfer of CBA and BALB/c spleens were TdT positive and 20 alpha-hydroxysteroid dehydrogenase positive, respectively. In thymus-bearing mice, but not in nude mice, the transfer of preleukemic spleen cells gave lymphomas earlier than did transfer of bone marrow cells. This suggests that the more mature lymphoid cell population in the spleen of thymus-bearing mice may allow leukemic transformation to occur more rapidly than do the less mature cells in the bone marrow. In one-third of the cases, the virus produced by the preleukemic cells transferred induced new lymphomas involving recipient host cells. These de novo-induced lymphomas were all TdT positive. We suggest that leukemic transformation of TdT-positive cells may occur through a different mechanism than does transformation of cells bearing the 20 alpha-hydroxysteroid dehydrogenase marker.

20-Hydroxysteroid Dehydrogenases↗
PubMed1984

Prognostic significance of terminal transferase activity and glucocorticoid receptor levels in acute myeloid leukemia.

A retrospective study was undertaken to evaluate terminal transferase activity and glucocorticoid receptor content as predictors of prognosis in 52 adult patients with acute myeloid leukemia (AML). Eighteen patients who had detectable levels of TdT in their leukaemic cells (greater than or equal to 0.1 unit microgram-1 DNA), had a higher complete remission rate than patients with low TdT activity. Patients below 60 years with increased TdT activity also had longer survival as compared to those with low TdT levels. By combining cytochemical analysis of peroxidase and immunocytochemical staining for TdT it was possible to show that the enzyme was located in leukaemic cells of myeloid origin. Leukemias of monocytic origin had no detectable TdT activity in 10/11 cases. The cellular content of the cytoplasmic glucocorticoid receptor varied from 0 to 2.8 fmol micrograms-1 DNA. There was no difference in receptor content between the different FAB subgroups. High levels of the receptor (greater than or equal to 0.22 fmol microgram-1 DNA) were positively correlated with the remission rate. Patients with TdT levels of greater than or equal to 0.1 unit microgram-1 DNA and a glucocorticoid receptor concentration of greater than or equal to 0.22 fmol microgram-1 DNA had significantly higher remission (P = 0.001) and survival rates (P = 0.007) compared with those with undectectable levels of both TdT and low receptor content. It is thus concluded that combined measurements of TdT and the glucocorticoid receptor are useful predictors of prognosis in AML.

Adult↗
PubMed1983

A study of the reproducibility of the diagnostic criteria for acute leukaemia.

The Leukaemia Group of Middle Sweden recently started a new multicentre study of treatment of adult patients with acute leukaemia from 6 centres. The criteria for the diagnosis, subclassification, degree of leukaemic bone marrow infiltration, remission and relapse are to be used by the morphologists of 6 different pathology departments. The reproducibility of the criteria has been studied by 3 of the morphologists concerned, in a retrospective review of a strictly consecutive series of 79 adult patients treated at Södersjukhuset, Stockholm, Sweden, in the years 1978 to 1981. The results show that the reproducibility of the criteria and the concordance of the morphologists when using them increased when the criteria were made more detailed and precise.

Acute Disease↗
PubMed1982

Different T-cell subtypes are associated with pathologically distinct forms of Moloney leukemia virus (M-MuLV)-induced lymphoma.

The T-cell enzyme markers, terminal deoxy-nucleotidyltransferase (TDT) and 20 alpha hydroxysteroid dehydrogenase (20 alpha SDH), were used to classify lymphomas induced by the Moloney leukemia virus (M-MuLV). Different subtypes of T cells were shown to be involved in different types of lymphoma. Thymomas were TdT-positive and grew as subcutaneous solid tumors at the site of inoculation. Spleen cells from mice with generalized lymphoma were of two types. In the majority of cases the lymphomas consisted of 20 alpha SDH-positive cells that homed to spleen and lymph nodes upon transplantation. In a few cases the cells of enlarged spleens were TdT-positive and, like the TdT-positive thymomas, could be transplanted as subcutaneous tumors. Thus, TdT-positive and 20 alpha SDH-positive T-cell lymphomas can be distinguished by their homing properties. Preleukemic thymus cells from M-MuLV inoculated mice can, after transfer to 400 -R irradiated syngeneic hosts, induce new lymphomas by virus release or grow in an autonomous fashion in the recipients. Whether of donor or recipient type, these lymphomas are TdT-positive. In contrast, preleukemic bone marrow cells give lymphomas of donor type which are as heterogeneous for T-cell enzymes as are lymphomas induced by neonatal inoculation of M-MuLV.

20-Hydroxysteroid Dehydrogenases↗
PubMed1981

Glucocorticoid receptor concentrations and terminal transferase activity as indicators of prognosis in acute non-lymphocytic leukaemia.

Activity of terminal deoxynucleotidyl transferase (TdT), adenosine deaminase, and 5'nucleotidase and the cellular concentration of glucocorticoid (dexamethasone) receptor were determined in 25 patients with acute non-lymphocytic leukaemia. All patients were treated according to a common protocol. Increased activity of TdT (greater than 0.1 unit/microgram DNA) was found in 11 patients. This group of patients was shown to have higher remission and survival rates (p = 0.06) compared with patients with low activity of TdT. The glucocorticoid receptor concentration of the leukaemic blast cells ranged from 0 to 0.94 fmol/microgram DNA. Thirteen patients had blast cells with a glucocorticoid receptor concentration over 0.22 fmol/microgram DNA. These patients had significantly increased remission and survival rates (p = 0.006) compared with those with a low receptor concentration. This finding cannot be explained by a difference in sensitivity to glucocorticoids since these were not used as therapeutic agents. Adenosine deaminase and 5'nucleotidase activities both varied within two orders of magnitude. No correlation could be found between activities of these enzymes and remission or survival rate. These results show that measurements of TdT activity and the glucocorticoid receptor concentration yield valuable prognostic information in acute non-lymphocytic leukaemia.

5'-Nucleotidase↗
PubMed1981

Decay of Moloney leukemia virus production after enucleation of chronically infected mouse cells.

The effect of enucleation of synthesis of Moloney leukemia virus was studied in chronically infected YACIR-A9 mouse hybrid cells. The synthesis of infectious virus decreased gradually until, 12 h after enucleation, virtually no infectious virus was produced. As determined by particle-bound p30 and reverse transcriptase, cytoplasts produced a low level of noninfectious viral particles. Thus, the assembly of virus particles does not appear to be wholly dependent on the presence of the cell nucleus. In contrast, production of infectious particles shows an absolute requirement for the cell nucleus.

Animals↗
PubMed1980

Deoxyuridine triphosphate pools after polyoma virus infection.

The synthesis of polyoma DNA in virus-infected 3T6 mouse fibroblasts is discontinuous with the intermediate formation of short Okazaki fragments. Hydroxyurea, an inhibitor of the enzyme ribonucleotide reductase, inhibits polyoma DNA synthesis, as measured by incorporation of radioactive thymidine. In the inhibited state, almost all incorporation occurs into short fragments. We investigated to what extent formation of short DNA fragments might be the result of incorporation of deoxyuridine triphosphate (dUTP) into DNA, followed by excision and repair reactions. We devised a sensitive enzymatic method for measuring dUTP in cell extracts which allows the determination of the dUTP pool when this pool amounts to between 0.1 and 2% of the dTTP pool. No dUTP was detected in growing mouse fibroblasts. After infection with polyoma virus cell extracts contained 0.4% dUTP (of dTTP) at the peak of DNA synthesis. Addition of hydroxyurea at this point led to a disappearance of dUTP. We conclude that dUTP incorporation can contribute only minimally to the generation of short fragments during polyoma DNA synthesis.

Animals↗
PubMed1980

Control of nucleotide pools in mammalian cells.

The deoxyribonucleoside triphosphates (dNTPs) are produced via reduction of the corresponding nucleoside diphosphates and subsequent phosphorylation. The reduction step is catalyzed by the enzyme ribonucleoside diphosphate reductase, an enzyme which is induced in S phase cells. The activity and specificity of this enzyme is controlled by dNTPs and ATP, and this feedback mechanism provides a stringent control of the concentrations of the dNTPs themselves. The pools of the dNTPs vary during the cell cycle and are largest is S phase cells. Moreover, in S phase cells, the difference between the largest pool (dCTP) and the smallest pool (dGTP), is about 20-fold. Also, the pools are compartmentalized into cytoplasmic and nuclear pools, and this compartmentalization is most pronounced in S phase cells. In such cells, the total nuclear concentration of dNTPs is about micronM. Mainly by use of virus-infected cells, results were obtained which indicate a direct involvement of a deoxycytidine nucleotide in the regulation of DNA synthesis.

Animals↗